DRY AMD
Study: A Multiple Dose Study of Repeat Intravitreal Injections of GEM103 in Dry Age-related Macular Degeneration
Clinicaltrials.gov Identifier: NCT04643886
Sponsor: Gemini Therapeutics, Inc.
Purpose: This study is designed to investigate the safety, PK/PD, biomarker and early clinical effects of repeat GEM103 IVT injections.
Design: randomized, parallel assignment, no masking
Number of Patients: 60
Inclusion Criteria: At least 50 years old at the time of signed informed consent. Must have one of the following genetic profiles: Genetic Profile A; Genetic Profile B. BCVA in the study eye of 24 to 83 letters using ETDRS Chart Visual Acuity (VA) scale (approximately equivalent to Snellen VA of 20/25 to 20/320). Confirmed diagnosis of GA in the study eye where total size of all GA lesions in the study eye must be within 0.5 to 15.01- and 7- disc areas. Sufficiently clear ocular media and able to cooperate with ophthalmic visual function testing and anatomic assessment in the study eye. Understands the full nature and purpose of the study and provides informed consent prior to initiation of any study procedure; all subjects with a reproductive potential must agree to use effective contraceptive methods through the end of study (EOS) visit.
Exclusion Criteria: Presence of the following ocular conditions - in the study eye: Any history of exudative Age-related Macular Degeneration or choroidal neovascularization. Any active ocular disease or condition that could confound the assessment of the macula or be a contraindication to IVT injection. Any intraocular surgery, with the exception of stable intraocular lens replacement surgery more than 3 months prior to consent. Aphakia or complete absence of the posterior capsule. History of laser therapy to the macula or fundus or extensive laser to the retina. Prior corneal transplant. Presence of any of the following ocular conditions - in either eye: History of herpetic infection. Concurrent disease that could require medical or surgical intervention during the study period. Active uveitis and/or vitritis (grade: trace or above). History of idiopathic or autoimmune-associated uveitis. Active blepharitis, conjunctivitis, keratitis, episcleritis, scleritis, or endophthalmitis. Any ophthalmologic condition that reduces the clarity of the media and that, in the opinion of the Investigator, interferes with ophthalmologic examination. In the opinion of the Investigator, the subject has any prior or ongoing medical condition (e.g., ocular other than dry AMD, systemic, psychiatric) or clinically significant screening laboratory value that may present a safety risk, interfere with study compliance or study follow-up, or confound data interpretation throughout the follow-up period. Female subjects must not be pregnant or lactating, nor plan to become pregnant during the study. Current use of medications known to be toxic to the lens, retina, or optic nerve. Use of any investigational new drug or other experimental treatment in the last 6 months, and/or receipt of any prior gene therapy (e.g., AAV) or ocular device implantation (other than PCIOL placement following cataract surgery)
Information: clinicaltrials@geminitherapeutics.com
Study: Safety and Tolerability of RPESC-derived RPE Transplantation in Patients With Dry Age-related Macular Degeneration (AMD)
Clinicaltrials.gov Identifier: NCT04627428
Sponsor: Luxa Biotechnology, LLC
Purpose: The main objective of the study is evaluation of the safety and tolerability of RPESC-RPE-4W as therapy for dry AMD.
Design: nonrandomized, sequential assignment, no masking
Number of Patients: 18
Inclusion Criteria: Clinical diagnosis of dry AMD. Ability to understand and give informed consent. Adult male or female >55 years of age. Medically suitable to undergo vitrectomy and subretinal injection (>60% on Karnofsky scale). Postmenopausal if female (expected to be common for the age limitation), or the female partner of a male subject unable to father children. If male, willing to use barrier and spermicidal contraception during the study.
Exclusion Criteria: Allergy or hypersensitivity to dilation drops or fluorescein. Active major medical conditions limiting ability to participate in the study. Active malignancy or treatment with chemotherapy. Systemic immunosuppressant therapy within past 6 months. History of toxoplasmosis, retinal histoplasmosis or tuberculosis. Receipt of investigational product (IP) in a clinical trial within prior 6 months. Any other medical condition, which, in the investigator's judgment, will interfere with the subject's ability to comply with the protocol, compromises subject safety, or interferes with the interpretation of the study results. Pregnant or nursing females.
Information: jeffreystern@luxabiotech.com
Study: Effect of Oral Curcumin Supplementation in Dry Age-related Macular Degeneration (AMD) Patients
Clinicaltrials.gov Identifier: NCT04590196
Sponsor: University of Illinois at Chicago
Purpose: Oral Longvida curcumin has been shown to accumulate in the retina of human subjects within 10 days of supplementation. This study aims to investigate the duration of oral curcumin supplementation needed to see clinical impact in reducing volume and number of drusen and decreasing choriocapillaris density loss or flow impairment in dry AMD patients.
Design: parallel assignment, quadruple masking
Number of Patients: 40
Inclusion Criteria: Age >50 years old BCVA 20/20 to 20/400 dry AMD with many large (>300 μm in diameter and more than 100 μm in height) soft drusenoid PEDs
Exclusion Criteria: presence (or history) of significant geographic atrophy or choroidal neovascularization in either eye; history of eye surgery (other than cataract extraction) within 90 days, history of BRVO/CRVO, Macular hole, pathologic myopia, uveitis, pseudovitelliform maculopathy will be excluded.
Information: mehta@uic.edu
Study: FOCUS: First in Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects With Dry AMD
Clinicaltrials.gov Identifier: NCT03846193
Sponsor: Gyroscope Therapeutics
Purpose: This is an open-label first-in-human phase 1/2 multicenter study of GT005 in subjects with macular atrophy due to AMD.
Design: Nonrandomized, sequential assignment
Number of Patients: 35
Inclusion Criteria: Able and willing to give consent to study participation. Presence of bilateral GA due to AMD on colour fundus photography (CFP). GA lesions total size in the study eye must be ≥1.25mm2 and ≤17.5mm2 for the study eye. The GA lesion in the study eye must reside completely within the FAF fundus image. Cohorts 1 to 3: BCVA of ≤50 letters (6/36 Snellen acuity equivalent or worse) using ETDRS charts in the study eye Cohort 4: BCVA of ≥34 letters (20/200 Snellen acuity equivalent or better) using ETDRS charts in the study eye. Aged ≥18 years. Able to attend all study visits and complete the study procedures. Women of child-bearing potential need to have a negative urine pregnancy test within two weeks prior to receiving the drug.
Exclusion Criteria: Evidence or history of neovascular AMD or diabetic retinopathy [either eye]. History of significant ocular surgery which, in the opinion of the Investigator, may either put the subject at risk if participating in the study, or may influence the results of the study, or the subject's ability to participate in the study [either eye]. Concomitant disease(s) limiting the subject's ability to undergo retinal surgery [study eye]. Clinically significant cataract that may require surgery during the study period [study eye]. Any sign of macular changes that might indicate a separate pathology independent of AMD, such as pathological myopia (eg, >6 diopters of myopia) or history of significant amblyopia [either eye]. Any other significant ocular or non-ocular disease/disorder which, in the opinion of the Investigator, may either put the subject at risk if participating in the study, or may influence the results of the study, or the subject's ability to participate in the study [either eye]. Having a contraindication to oral prednisolone/prednisone, such as gastric ulcer, or significant side effects. Current participation in another research study, including observational studies. Participation in another research study involving an investigational product in the previous 12 weeks or received a gene/cell based therapy at any time previously [either eye]. Any known sensitivity to GT005 formulation component or excipients. Unwilling to use two forms of contraception (one of which being a barrier method) 90 days for men and 30 days for women post-dosing, if relevant. History or presence of cutaneous squamous cell carcinoma.
Information: clinicaltrials@gyroscopetx.com
Study: HORIZON: A Phase 2 Study to Evaluate the Safety and Efficacy of Two Doses of GT005
Clinicaltrials.gov Identifier: NCT04566445
Sponsor: Gyroscope Therapeutics
Purpose: The purpose of this clinical study is to evaluate the safety and efficacy of two doses of GT005 administered as a single subretinal injection in subjects with geographic atrophy secondary to age-related macular degeneration (AMD).
Design: Randomized, parallel assignment
Number of Patients: 180
Inclusion Criteria: Able and willing to give written informed consent. Age ≥55 years. Have a clinical diagnosis of bilateral GA secondary to AMD as determined by the Investigator. GA lesion(s) within an acceptable size on FAF, in the study eye. The GA lesion in the study eye must reside completely within the FAF image. Have a BCVA of 34 letters (6/60 or 20/200 Snellen acuity equivalent), using ETDRS charts, in the study eye. Meet one of the prespecified AMD genetic subgroup criteria. Able to attend all study visits and complete the study procedures. Women of child-bearing potential must have a negative pregnancy test within 2 weeks prior to randomization or provide documentation of being surgically sterilized.
Exclusion Criteria: Carriers of excluded genetic variants. Have evidence or history of CNV in either eye. Presence of moderate/severe or worse non-proliferative, diabetic retinopathy in the study eye. Have history of vitrectomy, sub-macular surgery, or macular photocoagulation in the study eye. Have clinically significant cataract that may require surgery during the study period in the study eye. Presence of moderate to severe glaucomatous optic neuropathy, uncontrolled IOP, use of two or more topical agents to control IOP; or a history of glaucoma-filtering surgery in the study eye. Axial myopia of greater than -8 diopters in the study eye. Have received any investigational product for the treatment of GA within the past 6 months or 5 half-lives (whichever is longer), other than nutritional supplements such as the age-related eye disease study (AREDS) formula. Have received a gene or cell therapy at any time. Have a contraindication to the corticosteroid regimen. Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant. Have a history or presence of cutaneous squamous cell carcinoma. Have any other significant ocular or non-ocular medical or psychiatric condition which, in the opinion of the Investigator, may either put the subject at risk or may influence the results of the study.
Information: clinicaltrials@gyroscopetx.com
Study: EXPLORE: A Phase 2 Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (EXPLORE)
Clinicaltrials.gov Identifier: NCT04437368
Sponsor: Gyroscope Therapeutics
Purpose: The purpose of this clinical study is to evaluate the safety and efficacy of two doses of GT005 administered as a single subretinal injection in subjects with geographic atrophy secondary to age-related macular degeneration (AMD).
Design: Randomized, parallel assignment
Number of Patients: 75
Inclusion Criteria: Able and willing to give written informed consent. Age ≥55 years. Have a clinical diagnosis of GA secondary to AMD as determined by the Investigator. GA lesion(s) within an acceptable size on FAF, in the study eye. The GA lesion in the study eye must reside completely within the FAF image. Have a BCVA of 34 letters (6/60 and 20/200 Snellen acuity equivalent) or better, using ETDRS charts, in the study eye. Serum Complement Factor I level below the lower limit of normal of the selected assay. Have a rare genetic variant of the CFI gene, defined as a minor allele frequency of <1%. Able to attend all study visits and complete the study procedures. Women of child-bearing potential must have a negative pregnancy test within 2 weeks prior to randomization.
Exclusion Criteria: Have evidence or history of CNV in either eye. Presence of moderate/severe or worse nonproliferative diabetic retinopathy in the study eye. Have history of vitrectomy, submacular surgery, or macular photocoagulation in the study eye. Have clinically significant cataract that may require surgery during the study period in the study eye. Presence of moderate to severe glaucomatous optic neuropathy in the study eye, uncontrolled intraocular pressure (IOP), use of two or more topical agents to control IOP, or a history of glaucoma-filtering surgery. Axial myopia of greater than -8 diopters in the study eye. Have any other significant ocular or nonocular medical or psychiatric condition which, in the opinion of the Investigator, may either put the subject at risk or may influence the results of the study. Have a contraindication to oral prednisolone/prednisone. Have received any investigational product for the treatment of GA within the past 6 months, or 5 half-lives (whichever is longer) other than nutritional supplements such as the AREDS formula. Have received a gene or cell therapy at any time. Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant. Have a history or presence of cutaneous squamous cell carcinoma.
Information: clinicaltrials@gyroscopetx.com
Study: Study of Subretinal Implantation of Human Embryonic Stem Cell-Derived RPE Cells in Advanced Dry AMD
Clinicaltrials.gov Identifier: NCT02590692
Sponsor: Regenerative Patch Technologies, LLC
Purpose: The phase I/IIa clinical trial is designed to assess the feasibility of delivery and safety of Human Embryonic Stem Cell-Derived RPE Cells on a parylene membrane (CPCB-RPE1) in patients with advanced, dry age-related macular degeneration.
Design: Single group, no masking
Number of Patients: 16
Inclusion Criteria: Patients able to understand and willing to sign the informed consent. Adult male or female patients with the age of 55 to 85 (inclusive) years who are not employees of the trial sites. In sufficiently good health to reasonably expect survival for at least five years after treatment. Clinical findings consistent with advanced dry AMD with evidence of one or more areas of ≥1.25 square millimeter of geographic atrophy involving the central fovea. Geographic atrophy defined as attenuation or loss of RPE as observed by biomicroscopy, OCT, or FAF. The best-corrected visual acuity (BCVA) of the eye to receive the implant will be equal or worse than 20/200 in the first half of the study patients and between 20/80 and 20/400 (inclusive) in the second half of the patients. The BCVA of the eye that is NOT to receive the implant will be better or equal to the eye that will receive the implant. Medically suitable to undergo pars plana vitrectomy and the surgical implant procedure, including being able to position post-operatively and use post-operative medications as required. Medically suitable for general anesthesia or monitored intravenous sedation, if needed. Patients who are pseudophakic or aphakic in the study eye. If designated as an organ donor, willing to forego live organ donation. Willing to consent to the post-mortem removal of the implant from the treated eye for the sponsor's analysis. The patient may also elect to donate the implanted and fellow, untreated eye, for histological analysis. Able to understand the requirements of the study and willing and able to participate in long term follow up.
Exclusion Criteria: Presence of active or inactive choroidal neovascularization (CNV). Presence or history of retinal dystrophy, retinitis pigmentosa, chorioretinitis, central serous choroidopathy or any other inflammatory ocular disease except dry eye syndrome. Presence or history of severe, end-stage corneal dystrophy. History of steroid induced ocular hypertension or glaucoma. Presence of moderate to severe glaucomatous optic neuropathy in the study eye, uncontrolled IOP, use of two or more topical agents to control intraocular pressure; history of glaucoma-filtering surgery. Presence of moderate to severe non-proliferative diabetic retinopathy in the study eye. Presence of any proliferative diabetic retinopathy in the study eye. Presence of uncontrolled diabetes mellitus (HbA1c >8) at the time of screening. History of retinal detachment or retinal detachment repair in the study eye other than peripheral retinal tears or holes treated exclusively with laser or cryotherapy. Presence of any other sight-threatening ocular disease. History of cognitive impairments or dementia which may impact the patient's ability to participate in the informed consent process and to appropriately complete evaluations. History of any immunodeficiency. Evidence of herpetic or other viral eye disease. Any current use of immunosuppressive therapy other than intermittent or low dose corticosteroids. Participation within previous 3 months in any clinical trial of a drug by ocular or systemic administration (within previous 18 months for sustained release products). Axial myopia of greater than -8 diopters in the eye that is to be implanted. Axial length greater than 28 mm in the eye that is to be implanted. History of malignancy within the past 5 years (with the exception of successfully treated [excised] basal cell carcinoma [skin cancer] or successfully treated squamous cell carcinoma of the skin). History of myocardial infarction in previous 12 months. Alanine transaminase/aspartate aminotransferase (ALT/AST) >3.0 times the upper limit of normal or any known liver disease. Renal insufficiency, as defined by estimated creatinine clearance of < 45 mL/min. A positive (or "reactive") test for HIV, or Hepatitis B, or Hepatitis C. A hemoglobin concentration of less than 10 gm/dL, a platelet count of less than 100K/µL or an absolute neutrophil count of less than 1000/µL at study entry. Ocular lens removal within the previous 6 weeks in either eye. Any other ocular surgery in the study eye in the previous 3 months. If female, pregnancy, the wish to become pregnant, or lactation. Any other medical condition, which, in the Investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromises patient safety, or interferes with the interpretation of the study results.
Study: A Staged Study of the Safety and Effectiveness of ASP7317 in Senior Adults Who Are Losing Their Clear, Sharp Central Vision Due to Dry Age-related Macular Degeneration
Clinicaltrials.gov Identifier: NCT03178149
Sponsor: Astellas Institute for Regenerative Medicine
Purpose: This study is looking at a new treatment for slowing or reversing dry AMD, called ASP7317. ASP7317 is a specially created type of cells derived from stem cells. ASP7317 cells are injected into the macula of the eye. Immunosuppressive medicines (called IMT) are also taken around the time of injection of the cells to prevent the body from rejecting them.
Design: Randomized, parallel assignment, no masking
Number of Patients: 150
Inclusion Criteria: Subject has atrophy secondary to AMD in the study eye. Subject has the border of the area of definite decreased autofluorescence (DDAF) in the study eye, within the vascular arcades (criterion not applicable for subjects in dose escalation stage). Subject has a best corrected visual acuity (BCVA) score ≤37 early treatment diabetic retinopathy study (ETDRS) letters, in the study eye, at the second assessment during the screening visit between 4 and 23 ETDRS letters. In the dose escalation stage for the first dose cohort only, the study eye must be between light perception and ≤ 23 ETDRS letters at the second assessment during the screening visit. Subject has stable BCVA, in the study eye, to ensure stability of the visual acuity measures for study analyses (criterion not applicable for subjects in dose escalation stage). Subject has spectral domain-optical coherence tomography (SD-OCT) scans obtained of the study eye at the screening visit of suitable quality for grading retinal microstructures. Subject, at the screening visit, must have in the study eye an area with reduced retinal function and evidence of structural retinal preservation between the border of the area of atrophy and the vascular arcades, as determined by the subject selection committee (SSC) (criterion not applicable for subjects in dose escalation stage). Subject is recommended by the SSC for trial participation.
Exclusion Criteria: The following conditions are exclusionary if present in the study eye, unless otherwise specified. Foveal sparing as determined by either of the following methods (criterion not applicable for subjects in dose escalation stage): Any of the 9 loci in central square of the macula test grid with ≥ 0 dB sensitivity based on microperimetry testing at the prescreening or screening visit assessments. Presence of potentially viable photoreceptors, as evidenced by presence of ellipsoid zone (EZ), ≤ 250. Subject has evidence of prior or active choroidal neovascularization (CNV). Evidence of CNV will be assessed by the image reading center through review of the screening fundus photographs, fluorescein angiography (FA) and SD-OCT images. Evidence of CNV seen on 1 or more imaging modality is exclusionary. Subject has macular atrophy due to causes other than AMD. Subject has pathologic myopia defined as a spherical equivalent of > 8.00 diopters or axial length > 28 mm at the prescreening or screening visit, or myopic macular degeneration. Subject has a contraindication to pupil dilation. Subject has any other current sight-threatening ocular disease. Subject has presence of a posterior staphyloma. Subject has a current or prior history of optic neuropathy. Subject has presence of a macular hole. Subject has presence of macular schisis. Subject has a current or prior history of retinal dystrophy, retinitis pigmentosa, chorioretinitis, central serous choroidopathy, diabetic retinopathy, diabetic macular edema, vasoocclusive disease or other retinal vascular disease (e.g., compromised blood-retinal barrier) or retinal degenerative disease other than AMD. Subject has a prior history of retinal detachment within the vascular arcades. Subject has nevus of Ota (oculodermal melanocytosis), a choroidal pigmented lesion showing characteristics associated with high risk of malignancy (e.g., orange pigmented or elevated lesions) or a choroidal nevus within the macula. Subject has presence of submacular scarring. Subject has presence of an ocular toxoplasmosis scar or suspected active infection (or presence of elevated immunoglobulin M [IgM] toxoplasmosis titer). Subject has an abnormality of vitreoretinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) which can interfere with measurement of macular thickness or with the potential for macular structural damage. Subject has an intraocular pressure (IOP) of < 6 mmHg at the screening or first baseline (day -21) visits. Subject has presence of glaucomatous optic atrophy or uncontrolled intraocular pressure (IOP), or is using more than 2 agents to control IOP. Subject has active or history of uveitis. Subject has obscured ocular media opacity (e.g., corneal scars, lens opacities, vitreous abnormalities, etc.) at the screening or first baseline (day -21) visits such that reliable evaluations of the posterior segment cannot be performed. Subject has any other current ocular condition that can interfere with the assessment of disease progression including but not limited to accumulation of intraretinal fluid, subretinal fluid, sub-retinal pigment epithelial/epithelium (RPE) fluid or cystoid macular edema. Subject has monocular vision. Subject has a history of ocular cancer in either eye.
Information: astellas.registration@astellas.com
Study: First in Human Study to Evaluate the Safety and Tolerability of GEM103 in Geographic Atrophy Secondary to Dry Age Related Macular Degeneration
Clinicaltrials.gov Identifier: NCT04246866
Sponsor: Gemini Therapeutics, Inc.
Purpose: The study is designed to identify the maximum tolerated dose (MTD) for intravitreal (IVT) administration of GEM103 in subjects with geographic atrophy (GA) secondary to dry AMD. Safety and tolerability of a single dose of GEM103 will be assessed based on the occurrence of dose-limiting toxicities (DLTs). Each subject will be followed for safety, pharmacokinetic (PK), clinical, and biomarker evaluations. Three escalating dose cohorts are planned.
Design: Nonrandomized, sequential assignment, no masking
Number of Patients: 12
Inclusion Criteria: At least 50 years old at the time of signed informed consent. Genetic variant eligibility. Able to cooperate sufficiently for adequate ophthalmic visual function testing and anatomic assessment and provide informed consent prior to initiation of any study procedure. Best corrected visual acuity (BCVA) in study eye between 5-35 letters. Confirmed diagnosis of central GA in the study eye and eligible total GA lesion size.
Exclusion Criteria: Carriers of specified high-genetic risk AMD variants. Presence of the following ocular conditions - in the study eye: Exudative AMD or choroidal neovascularization (CNV); Any ocular disease or condition that could impact the subject's ability to participate in the study or be a contraindication to IVT injection; Intraocular surgery (including intraocular lens replacement surgery) within 3 months prior to consent. Presence of any of the following ocular conditions - in either eye: History of herpetic infection; Ongoing treatment with antiangiogenic therapies in the fellow eye or completed treatment in the study eye. Any prior or ongoing medical condition (e.g. ocular other than dry AMD, systemic, psychiatric) or clinically significant screening laboratory value that may present a safety risk, interfere with study compliance, interfere with consistent study follow-up, or confound data interpretation throughout the longitudinal follow-up period. Female subjects must not be pregnant or lactating. Current use of medications known to be toxic to the lens, retina, or optic nerve.
Information: clinicaltrials@geminitherapeutics.com
Study: Carbidopa-Levodopa in Dry AMD With Geographic Atrophy
Clinicaltrials.gov Identifier: NCT03451500
Sponsor: Robert W. Snyder, MD, PhD, PC
Purpose: The Investigators will evaluate the safety and tolerability of carbidopa-levodopa in patients with Neovascular AMD and measure the effects on visual acuity and retinal abnormalities due to "wet" (neovascular) AMD. The Investigators will evaluate the safety and tolerability of carbidopa-levodopa in patients with Dry AMD and Geographic Atrophy, and measure the effects on visual acuity, area of geographic atrophy and other retinal abnormalities due to "dry" AMD.
Design: Parallel assignment, randomized, prospective, placebo-controlled
Number of Patients: 7
Inclusion Criteria: A diagnosis of dry AMD with geographic atrophy in 1 or both eyes. In patients with geographic atrophy in both eyes, the eye with the larger area of geographic atrophy will be designated eye A and the eye with the smaller area of geographic atrophy will be designated eye B. Normal or dry AMD of any grade in the second eye; Age 50-85 years; Willingness to maintain AREDS vitamin supplements throughout the study, or remain off these supplements for the duration of the study, if not taking them prior to the study; signed informed consent.
Exclusion Criteria: Any previous or current use of L-DOPA containing medication or dopamine agonist medication, or any planned use of any of these agents, except for study medication, during the study; Concurrent use of monoamine oxidase (MAO) inhibitors; Any eye condition, disease, or history of trauma in either eye, which can impair vision, except cataract or cataract surgery; BCVA worse than 20/100 in the eye with better BCVA; Current, or history of, neovascular AMD in either eye; Neurologic conditions which can impair vision; Parkinson's Disease; Significant orthostatic hypotension, defined as a drop in systolic blood pressure, immediately upon changing from the supine to standing position, of >19 mmHg, or a symptomatic drop in systolic blood pressure, immediately upon changing from the supine to standing position; Significant ECG abnormalities, as judged by the Investigator; Estimated glomerular filtration rate (eGFR) <20 ml/min; Liver enzymes >3x the upper limit of normal; HbA1C >9.0; Any other significant lab abnormalities, as judged by the Investigator. Women of childbearing potential; Known retinal hemorrhage; Subjects who are not fluent in English.
Study: Study of Photobiomodulation to Treat Dry Age-Related Macular Degeneration (LIGHTSITE III)
Clinicaltrials.gov Identifier: NCT04065490
Sponsor: LumiThera, Inc.
Purpose: This LIGHTSITE III study is a double-masked, sham-controlled, parallel design, prospective multi-site study for the use of PBM as a treatment for visual impairment in subjects with dry AMD.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 96
Inclusion Criteria: Male or female at least 50 years of age at Screening visit. ETDRS BCVA letter score of between 50* and 75* (Snellen equivalent of 20/100 to 20/32). *If the subject meets this criterion at the Screening Visit, but the Baseline BCVA letter score is between 48 and 77, the subject may be entered in the study. Diagnosis of dry AMD as defined by the presence of the following: Drusen that are intermediate in size or larger (63 μm or larger in diameter) with at least a few (3) being regular drusen and not pseudodrusen and/or geographic atrophy (GA) visible on 2 of the following: color fundus images, OCT and/or FAF, to be confirmed by the reading center. Able to communicate well with the Investigator and able to understand and comply with the requirements of the study. Informed of the nature of this study and has provided written, informed consent in accordance with institutional, local and national regulatory guidelines.
Exclusion Criteria: Current or history of neovascular maculopathy that includes any of the following (to be confirmed by the reading center): Choroidal neovascularization (CNV) defined as pathologic angiogenesis originating from the choroidal vasculature that extends through a defect in Bruch's membrane; Serous and/or hemorrhagic detachment of the neurosensory retina or retinal pigment epithelial (RPE); Retinal hard exudates (a secondary phenomenon resulting from chronic intravascular leakage); Subretinal and sub-RPE fibrovascular proliferation; Disciform scar (subretinal fibrosis). Presence of center involving GA within the central ETDRS 1 mm diameter at Screening, to be confirmed by the reading center. Media opacities, including cataracts, which might interfere with visual acuity or imaging in the study eye(s). Subjects should not be entered if there is likelihood that they will require cataract surgery in the study eye in the next 24 months. Posterior capsule opacification, which might interfere with visual acuity or imaging in the study eye(s). Subjects should not be entered if there is likelihood that they will require surgery in the study eye in the next 24 months. Invasive eye surgery (eg cataract, capsulotomy) on a qualifying eye within 3 months prior to screening. Ocular disorder or disease that partially or completely obstructs the pupil (eg posterior synechia in uveitis). Visually significant disease in any ocular structure apart from dry AMD (eg diabetic macular edema, glaucoma (using >2 eye drop medications, uncontrolled IOP and/or central/paracentral visual field loss), glaucoma surgery, active uveitis, active vitreous disease, intraocular tumor, retinal vascular diseases). Ocular disorder or disease other than dry AMD that could cause drusen (glomerulonephritis Type 2, Autosomal dominant drusen), GA (North Carolina dystrophy) or mitochondrial diseases (parafoveal petaloid GA, Stargardt disease). Presence or history of disease or condition affecting functional vision without obvious structural abnormalities (eg amblyopia, stroke, nystagmus). Serious medical illness that will prevent the subject from performing study activities (including cardiac, hepatic, renal, respiratory, endocrinologic, neurologic, or hematologic disease) or, in the judgement of the Investigator, is likely to require surgical intervention or hospitalization at any point during the study. Presence of or history of malignancy within the past 5 years other than non-melanoma skin or squamous cell cancer or cervical carcinoma in-situ. Is non-ambulatory. Presence or history of known light sensitivity to yellow light, red light, or near infrared radiation (NIR), or if they have a history of light activated CNS disorders (eg epilepsy, migraine). Use of any photosensitizing agent (eg topicals, injectables, oral) within 30 days of treatment without consulting subject's physician. History of drug, alcohol or substance abuse within 3 months prior to Screening. Has received an investigational drug or treatment with an investigational device within 3 months prior to Screening. If on any antioxidant or vitamin Age-Related Eye Disease Study (AREDS) supplement for dry AMD, has not been stabilized for a minimum of 1 month prior to Screening. Subjects are considered to be stable if they are taking the AREDS supplements consistently as prescribed by their treating doctor. Has received Low Vision Rehab/Therapy within 30 days prior to Screening or intends to receive during the study. Has an open sore(s) that may come in contact with the Valeda System, has periorbital skin erythema or is prone to such conditions with exposure to light. In the opinion of the Investigator, is unlikely to comply with the study protocol.
Information: ctedford@lumithera.com, ccroissant@lumithera.com
Study: Comparing the Efficacy and Safety of Biosimilar Candidate Xlucane Versus Lucentis in Patients With nAMD (XPLORE)
Clinicaltrials.gov Identifier: NCT03805100
Sponsor: Xbrane Biopharma AB; Stada Arzneimittel AG
Purpose: The objectives of the study are to demonstrate the equivalence of Xlucane to Lucentis in treatment of subjects with wet (ie, neovascular) age-related macular degeneration (wAMD).
Design: Randomized, parallel assignment, double masked
Number of Patients: 580
Inclusion Criteria: Written and signed informed consent form obtained at screening, before any study-related procedures. Willingness and ability to undertake all scheduled visits and assessments as judged by the investigator. Newly diagnosed, active subfoveal Choroidal Neovascularization (CNV) lesion secondary to age-related macular degeneration (AMD) in the study eye. Note: Active CNV indicates the presence of leakage as evidenced by Fluorescein Angiography (FA) and intra- or subretinal fluid as evidenced by Optical Coherence Tomography (OCT) which must be confirmed by the central reading center during Screening: The area of CNV must be ≥50% of the total lesion area in the study eye, and total lesion area ≤9.0 Disc Areas (DA) in size (including blood, scars, and neovascularization) as assessed by FA in the study eye. Best Corrected Visual Acuity (BCVA) of ≤73 and ≥49 ETDRS letter score in the study eye, using ETDRS chart (20/40 to 20/100 Snellen equivalent) at Screening. Fellow eye should not be expected to need any anti-VEGF treatment for the duration of study participation. Age ≥50 years at screening. Male and female subjects of childbearing potential must be willing to completely abstain or agree to use an appropriate method of contraception, from the time of signing informed consent and for the duration of study participation through 3 months, following the last dose of study drug.
Exclusion Criteria: Any previous intervention including pharmacological treatment, laser and/or surgery for wAMD in either eye; (exception: vitamin supplementation for AMD prevention). Any previous vitreoretinal surgery in the study eye for any cause. Any previous IVT treatment including any anti-VEGF medications, steroids and/or any other investigational medication in either eye. The use of long-acting steroids, either systemic or intraocular in any eye, in the 18 months before planned initiation of study treatment. (Note: Iluvien [fluocinolone acetonide intravitreal], current or planned implantation during the study, is prohibited.) Subfoveal fibrosis, atrophy or scarring extending >50% of total lesion area, in the study eye as assessed by the investigator at screening and confirmed by the central reading center prior to randomization. Choroidal neovascularization in either eye due to non-AMD causes (eg, DME, RVO, ocular histoplasmosis or trauma, etc.) as assessed by FA and confirmed by central reading center. Active or recent (within 28 days prior to randomization) intraocular, extraocular, and periocular inflammation or infection in either eye. History of idiopathic or autoimmune-associated uveitis in either eye. Infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye. Unmedicated intraocular pressure (IOP) ≥30 mmHg at Screening in either eye. Topical ocular corticosteroids administered for ≥30 consecutive days in the study eye within 90 days prior to Screening. Spherical equivalent of the refractive error in the study eye demonstrating more than 8 diopters of myopia. Corneal transplant or corneal dystrophy in the study eye. History of rhegmatogenous retinal detachment in the study eye. History of macular hole in the study eye. Retinal pigment epithelial tear or rip, involving the macula in the study eye as assessed by FA and confirmed by the central reading center. Current vitreous hemorrhage in the study eye. Subretinal hemorrhage that is ≥50% of the total lesion area in the study eye, or if the subretinal hemorrhage involves the fovea is 1 or more DA (≥2.54 mm2) in size in the study eye, as assessed by FA and confirmed by the central reading center. Other intraocular surgery (including cataract surgery) in the study eye within the 3 months prior to baseline. The yttrium aluminum garnet [YAG] posterior capsulotomy is allowed not later than 4 weeks prior to screening. Any concurrent intraocular condition in the study eye (eg, cataract or diabetic retinopathy) that, in the opinion of the investigator, could require treatment during the study period to prevent or treat loss of visual acuity. Significant media opacities (including cataract) in the study eye interfering with BCVA assessment or fundus imaging (FA/FP/OCT). Aphakia or absence of the posterior capsule in the study eye, unless it occurred as a result of a YAG posterior capsulotomy in association with prior posterior chamber intraocular lens implantation. Presence of advanced glaucoma or optic neuropathy that involve(s) or threaten(s) the central visual field in the study eye (as judged by the investigator). History of glaucoma filtering surgery or argon laser trabeculoplasty in the study eye (Exception: Laser iridotomy and selective laser trabeculoplasty are allowed). Uncontrolled ocular glaucoma or hypertension in the study eye, defined as IOP ≥25 mmHg despite treatment with anti-glaucoma medication. Any previous systemic anti-VEGF treatment (eg, bevacizumab). Contraindication for Lucentis (hypersensitivity to ranibizumab or to any of the study treatment excipients). Current treatment for active systemic infection. Females who are pregnant, nursing, planning a pregnancy during the study, or of childbearing potential and not using a reliable method of contraception and/or not willing to use a reliable method of contraception during their participation in the study. Participation in another clinical trial within the previous 3 months or any other clinical trial of anti-angiogenic drugs. Reasonable suspicion of other disease or condition that might render the subject at a high risk of treatment complications or otherwise confound interpretation of the study results (as judged by the investigator). PK subgroup only: Contraindication for additional blood sampling (as judged by the investigator).
Information: xbregistry@xbrane.com
Study: Safety and Efficacy Study of OpRegen for Treatment of Advanced Dry-Form Age-Related Macular Degeneration
Clinicaltrials.gov Identifier: NCT02286089
Sponsor: Cell Cure Neurosciences Ltd.
Purpose: The main objective of the study is evaluation of the safety and tolerability of OpRegen - human embryonic stem cell-derived retinal pigment epithelial (RPE) cells. The study will also include initial exploration of the ability of transplanted OpRegen cells to engraft, survive, and moderate disease progression.
Design: No masking, single group
Number of Patients: 24
Inclusion Criteria: Age 50 and older; Diagnosis of dry (non-neovascular) age related macular degeneration in both eyes; Funduscopic findings of dry AMD with progressive geographic atrophy in the macula; Best corrected central visual acuity equal or less than 20/200 in cohorts 1-3 and 20/64-20/250 in cohort 4 in the study eye by ETDRS vision testing; Vision in the non-operated eye must be better than or equal to that in the operated eye; Subjects with sufficiently good health to allow participation in all study-related procedures and complete the study follow-up period (medical records); Ability to undergo a vitreoretinal surgical procedure under monitored anesthesia care; Blood counts, blood chemistry, coagulation and urinalysis without abnormal significance; Negative for TB (cohort 4), HIV, HBC, and HCV, negative for CMV IgM and EBV IgM; Patients with no history of malignancy (other than a non-melanoma skin cancer). For cancers in remission for more than 5 years enrollment is allowed with concurred documented approval of principal investigator and oncologist prior to enrollment; Willing to defer all future blood and tissue donation; Able to understand and willing to sign informed consent.
Exclusion Criteria: Evidence of neovascular AMD by history, as well as by clinical exam, fluorescein angiography (FA), or ocular coherence tomography (OCT) at baseline in either eye; History or presence of diabetic retinopathy, vascular occlusions, uveitis, Coat's disease, glaucoma, cataract or media opacity preventing posterior pole visualization or any significant ocular disease other than AMD that has compromised or could compromise vision in the study eye and confound analysis of the primary outcome; History of retinal detachment repair in the study eye; Axial myopia greater than -6 diopters; At least 2 months following cataract removal in the study eye and Yttrium Aluminum Garnet (YAG) laser capsulotomy in the study eye in the past 4 weeks and any other ocular surgery in the study eye in the past 3 months prior to implantation; History of cognitive impairments or dementia; Contraindication for systemic immunosuppression; History of any condition other than AMD associated with choroidal neovascularization in the study eye (eg, pathologic myopia or presumed ocular histoplasmosis); Any type of systemic disease or its treatment, in the opinion of the Investigator, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk. Female; pregnancy or breastfeeding; Current participation in another clinical study. Past participation (within 6 months) in any clinical study of a drug administered systemically or to the eye. Currently receiving aspirin, aspirin containing products and/or any other coagulation modifying drugs which cannot be discontinued 7 days prior to surgery; History of cancer (other than a non-melanoma skin cancer). For cancers cured more than 5 years ago, enrollment is allowed with concurred documented approval of principal investigator and oncologist prior to enrollment.
Information: maria@cellcure.co.il; grazag@biotimeinc.com
Study: Alpha MSH in Ocular Disease
Clinicaltrials.gov Identifier: NCT03451578
Sponsor: Duke University
Purpose: The purpose of this study is gaining a better understanding of a molecule called alpha melanocyte stimulating hormone (alpha MSH) and its potential role in your retinal disease. Alpha MSH has been shown to have an important role in the regulation of ocular immunity in animal models of inflammatory retinal diseases and retinal dystrophies, and there may be a protective effect of alpha MSH. By studying the levels of alpha MSH in your eye, we may better understand its role in advanced dry macular degeneration. By studying the levels of this molecule, we hope to better understand if it may be a good target for future treatment.
Design: Single group, no masking, diagnostic
Number of Patients: 60
Inclusion Criteria: 60 years or older; diagnosis of advanced dry macular degeneration with foveal geographic atrophy; limited vision or blindness (20/100 or worse) in that eye; pseudophakia (prior cataract surgery in that eye).
Information: latoya.greene@duke.edu
Study: Study of Subretinal Implantation of Human Embryonic Stem Cell-Derived RPE Cells in Advanced Dry AMD
Clinicaltrials.gov Identifier: NCT02590692
Sponsor: Regenerative Patch Technologies, LLC
Purpose: The phase 1/2a clinical trial is designed to assess the feasibility of delivery and safety of human embryonic stem cell-derived RPE cells on a parylene membrane (CPCB-RPE1) in patients with advanced, dry age-related macular degeneration.
Design: Single Group Assignment, Open
Number of Patients: 20
Inclusion Criteria: Patients able to understand and willing to sign the informed consent. Adult male or female patients with the age of 55 to 85 (inclusive) years who are not employees of the trial sites; in sufficiently good health to reasonably expect survival for at least 5 years after treatment; clinical findings consistent with advanced dry AMD with evidence of 1 or more areas of ≥1.25 square millimeter of geographic atrophy involving the central fovea; geographic atrophy defined as attenuation or loss of RPE as observed by biomicroscopy, OCT, or FAF; the best-corrected visual acuity (BCVA) of the eye to receive the implant will be equal or worse than 20/200 in the first half of the study patients and between 20/80 and 20/400 (inclusive) in the second half of the patients. The BCVA of the eye that is NOT to receive the implant will be better or equal to the eye that will receive the implant; medically suitable to undergo pars plana vitrectomy and the surgical implant procedure, including being able to position postoperatively and use postoperative medications as required; medically suitable for general anesthesia or monitored intravenous sedation, if needed; patients who are pseudophakic or aphakic in the study eye; if designated as an organ donor, willing to forego live organ donation; willing to consent to the postmortem removal of the implant from the treated eye for the sponsor's analysis. The patient may also elect to donate the implanted and fellow, untreated eye, for histological analysis; able to understand the requirements of the study and willing and able to participate in long-term follow-up.
Exclusion Criteria: Presence of active or inactive choroidal neovascularization (CNV); presence or history of retinal dystrophy, retinitis pigmentosa, chorioretinitis, central serous choroidopathy or any other inflammatory ocular disease except dry eye syndrome; presence or history of severe, end-stage corneal dystrophy; history of steroid induced ocular hypertension or glaucoma; presence of moderate to severe glaucomatous optic neuropathy in the study eye, uncontrolled IOP, use of 2 or more topical agents to control intraocular pressure; history of glaucoma-filtering surgery; presence of moderate to severe nonproliferative diabetic retinopathy in the study eye; presence of any proliferative diabetic retinopathy in the study eye; presence of uncontrolled diabetes mellitus (HbA1c >8) at the time of screening; history of retinal detachment or retinal detachment repair in the study eye other than peripheral retinal tears or holes treated exclusively with laser or cryotherapy; presence of any other sight-threatening ocular disease; history of cognitive impairments or dementia which may impact the patient's ability to participate in the informed consent process and to appropriately complete evaluations; history of any immunodeficiency; evidence of herpetic or other viral eye disease; any current use of immunosuppressive therapy other than intermittent or low dose corticosteroids; participation within previous 3 months in any clinical trial of a drug by ocular or systemic administration (within previous 18 months for sustained release products); axial myopia of greater than -8 diopters in the eye that is to be implanted; axial length greater than 28 mm in the eye that is to be implanted; history of malignancy within the past 5 years (with the exception of successfully treated [excised] basal cell carcinoma [skin cancer] or successfully treated squamous cell carcinoma of the skin); history of myocardial infarction in previous 12 months; alanine transaminase/aspartate aminotransferase (ALT/AST) >3.0 times the upper limit of normal or any known liver disease; renal insufficiency, as defined by estimated creatinine clearance of <45 mL/min; a positive (or "reactive") test for HIV, or Hepatitis B, or Hepatitis C. A hemoglobin concentration of less than 10 gm/dL, a platelet count of less than 100K/µL or an absolute neutrophil count of less than 1000/µL at study entry; ocular lens removal within the previous 6 weeks in either eye; any other ocular surgery in the study eye in the previous 3 months; if female, pregnancy, the wish to become pregnant, or lactation; any other medical condition, which, in the Investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromises patient safety, or interferes with the interpretation of the study results.
Information: GAquino@laretina.com
Study: TOGA: Clinical Study to Evaluate Treatment with ORACEA for Geographic Atrophy
Clinicaltrials.gov Identifier: NCT01782989
Sponsor: Paul Yates, MD, PhD/MEDARVA
Purpose: To evaluate the efficacy and safety of ORACEA in the treatment of geographic atrophy due to dry age-related macular degeneration.
Design: Randomized, Parallel Assignment, Double-Blind, Treatment
Number of Patients: 286
Inclusion Criteria: Best-corrected visual acuity of 20/20 to 20/400 in the study eye; best-corrected visual acuity of hand motion or better in the nonstudy eye; clinical diagnosis of geographic atrophy secondary to nonexudative age-related macular degeneration in at least 1 eye (study eye); geographic atrophy lesions of ≥0.5 and ≤7.0 MPS disc areas.
Exclusion Criteria: History of or active presence of choroidal neovascularization secondary to exudative age-related macular degeneration in the study eye; history of or active presence of choroidal neovascularization secondary to exudative AMD in the nonstudy eye requiring any treatment within 12 months prior to day 0.
Information: pay2x@virginia.edu, aml7q@virginia.edu
Study: Evaluation of Oral Minocycline in the Treatment of Geographic Atrophy Associated With AMD
Clinicaltrials.gov Identifier: NCT02564978
Sponsor: National Eye Institute
Purpose: To see if minocycline is safe for people with GA and if it helps preserve their vision.
Design: Single Group Assignment, No Masking, Treatment
Number of Patients: 60
Inclusion Criteria: Participant must be 55 years or older; must have evidence of early or intermediate AMD as defined by characteristic presence of drusen and/or pigmentary changes; participant must be able to swallow capsules.
Exclusion Criteria: Participant is on ocular or systemic medications known to be toxic to the lens, retina or optic nerve (eg, ethambutol, chloroquine, or hydroxychloroquine); participant has a condition that would preclude participation in the study.
Information: Angela.kibiy@nih.gov
Study: METforMIN: Metformin for the Minimization of Geographic Atrophy Progression in Patients With AMD
Clinicaltrials.gov Identifier: NCT02684578
Sponsor: University of California, San Francisco
Purpose: To determine whether metformin, an FDA-approved drug for the treatment of type II diabetes, is a safe and effective treatment to decrease the progression of geographic atrophy in nondiabetic patients with age-related macular degeneration.
Design: Randomized, Safety/Efficacy, Parallel Assignment, Single-Blind, Treatment
Number of Patients: 186
Inclusion Criteria: Subject must have evidence of advanced dry AMD, defined by the characteristic presence of drusen and/or pigmentary changes, as well as geographic atrophy; subject must have clear ocular media and adequate pupillary dilation; study eye must have best corrected visual acuity (BCVA) of 20/20-20/400.
Exclusion Criteria: Subjects with insufficient baseline size of geographic atrophy, less than 1.25 mm2 (0.5 Macular Photocoagulation Study Disc Areas). GA is defined as 1 or more well-defined and often circular patches of partial or complete depigmentation of the RPE, typically with exposure of underlying choroidal blood vessels. Even if much of the RPE appears to be preserved and large choroidal vessels are not visible, a round patch of RPE partial depigmentation may be classified as early GA. The GA in the study eye must be able to be photographed in its entirety, and it must not be contiguous with any areas of peripapillary atrophy, which can complicate area measurements.
Information: eyestudy@ucsf.edu
WET AMD
NEW: Study: Safety and Tolerability Study of Suprachoroidal Injection of CLS-AX Following Anti-VEGF Therapy in Neovascular AMD (OASIS)
Clinicaltrials.gov Identifier: NCT04626128
Sponsor: Clearside Biomedical, Inc.
Purpose: To evaluate the safety and tolerability of suprachoroidally administered CLS-AX following intravitreal anti-VEGF therapy in subjects with neovascular age-related macular degeneration (AMD).
Design: Nonrandomized, sequential assignment, no masking
Number of Patients: 15
Inclusion Criteria: Diagnosis of neovascular age-related macular degeneration in the study eye. Active subfoveal choroidal neovascularization (CNV) secondary to AMD. Two or more prior anti-VEGF intravitreal injections. EDTRS BCVA score ≤ 75 and ≥ 20 letters.
Exclusion Criteria: Any active ocular disease, ocular disorders, prior ocular surgery or infection in the study eye other than nAMD. Other than IVT anti-VEGF treatments, no topical ocular or intraocular or periocular corticosteroid. IOP ≥ 25mmHg or cup-to-disc ratio >0.8. Active neovascular AMD in both eyes. Any clinically significant disorder or condition or disease (e.g. cardiovascular disease, uncontrolled hyperthyroidism, hyperglycemia, HbA1c >7.0, gastrointestinal bleed) that would make the participant unsuitable for the study. Currently enrolled in an investigational drug or device study or has used an investigational drug or device within 30 days or the screening visit.
NEW: Study: Effect of Intravitreally Administered AIV007 in Subjects With nAMD
Clinicaltrials.gov Identifier: NCT04422899
Sponsor: AiViva BioPharma, Inc.
Purpose: To determine safety, pharmacokinetics, and duration of effect of intravitreally administered AIV007 gel suspension in subjects with neovascular age-related macular degeneration.
Design: Nonrandomized, sequential assignment, no masking
Number of Patients: 24
Inclusion Criteria: Male or female subjects aged ≥ 50 years. Subjects must provide written informed consent before any study-related procedures are performed. Active subfoveal CNV in the study eye secondary to AMD that has previously been treated with at least 3 intravitreal injections of an anti-VEGF agent. BCVA in the study eye. Sentinel subjects only: 65 ETDRS letters (20/50 Snellen equivalent) or worse. All other subjects: 78 to 35 ETDRS letters (20/32 to 20/200 Snellen equivalent). Clear ocular media and adequate pupil dilation in both eyes to permit good quality photographic imaging.
Exclusion Criteria: Previous treatment for nAMD in the study eye, other than standard-of-care anti-VEGF IVT injection, eg, cell therapy, brachytherapy, gene therapy. Treatment with anti-VEGF in the non-study eye 2 weeks prior to baseline. Presence of diabetic retinopathy or glaucoma in either eye. Spherical equivalent for refractive error in the study eye of worse than 8.0 diopters of myopia (prior to cataract or refractive surgery). Presence of active infection or inflammation within 30 days prior to screening. Presence of contraindications to anti-VEGF treatment, including myocardial infarction, any cardiac event requiring hospitalization, treatment for acute congestive heart failure, transient ischemic attack, or stroke within the last 3 months of baseline. Uncontrolled hypertension or diabetes mellitus.
Information: office@AiViva.com
NEW: Study: Pivotal 1 Study of RGX-314 Gene Therapy in Participants With nAMD (ATMOSPHERE)
Clinicaltrials.gov Identifier: NCT04704921
Sponsor: Regenxbio Inc.
Purpose: This randomized, partially masked, controlled, Phase 2b/3 clinical study will evaluate the efficacy and safety of RGX-314 gene therapy in participants with nAMD. The study will evaluate 2 dose levels of RGX-314 relative to an active comparator. The primary endpoint of this study is mean change in best-corrected visual acuity (BCVA) of RGX-314 relative to ranibizumab. Approximately 300 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 300
Inclusion Criteria: Age ≥ 50 years and ≤ 89 years. An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye. Diagnosis of subfoveal CNV secondary to AMD in the study eye previously treated with anti-VEGF. Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye. Willing and able to provide written, signed informed consent for this study. Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry.
Exclusion Criteria: CNV or macular edema in the study eye secondary to any causes other than AMD. Subfoveal fibrosis or atrophy in the study eye. Any condition in the investigator's opinion that could limit VA improvement in the study eye. Active or history of retinal detachment in the study eye. Uncontrolled glaucoma in the study eye. History of intraocular surgery in the study eye within 12 weeks prior to Screening Visit 1. History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to Screening Visit 1. Prior treatment with gene therapy. Recent myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months.
Information: patientadvocacy@regenxbio.com
Study: A Study to Comparing SCD411 and Eylea in Subjects With Wet Age-related Macular Degeneration (AMD)
Clinicaltrials.gov Identifier: NCT04480463
Sponsor: Sam Chun Dang Pharm. Co. Ltd.
Purpose: SCD411 is being developed as a biosimilar to the reference product Eylea® (aflibercept), an anti-VEGF drug. The study aims to prove equivalence of SCD411 to Eylea in adults with wet AMD, and will look at safety, tolerance, effectiveness, immune response and the movement of the drug through the body.
Design: randomized, parallel assignment, quadruple masking
Number of Patients: 560
Inclusion Criteria: Provides written informed consent. Clinical diagnosis of wet (neovascular) age-related macular degeneration (AMD). BCVA (best corrected visual acuity) letter score of 73 to 35 at screening and prior to randomization. Women of child-bearing potential with negative serum pregnancy test at screening must agree to use protocol-defined methods of contraception throughout study until 3 months after last injection of aflibercept/SCD411. Males with female partners of child-bearing potential must agree to use protocol-defined methods of contraception and refrain from donating sperm throughout study until 3 months after last injection of aflibercept/SCD411.
Exclusion Criteria: Any prior eye (study eye and fellow eye) or systemic treatment or surgery for neovascular AMD, except dietary supplements or vitamins. Any prior or current treatment with another investigational agent to great neovascular AMD in the study eye, except dietary supplements or vitamins. Fellow eye shows signed of AMD that may need treatment during study period. Any prior treatment with anti-VEGF agents in both eyes. Blood, scars, atrophy, fibrosis, and neovascularization, based on assessment at screening. Central retina thickness of <300 µm in the study eye. Subretinal hemorrhage. Scar or fibrosis. Scar, fibrosis, or atrophy in the study eye. Presence of retinal pigment epithelial tears or rips involving the macular in the study eye. Cataract in the study eye that, in the Investigator's opinion, interferes with visualization of retina or retinal imaging. Inflammation outside the eyeball in either eye, or within the eyeball of the study eye. History of any vitreous hemorrhage in the study eye. History or clinical evidence of diabetic retinopathy, diabetic macular edema, or any other vascular disease. History of, treatment or surgery for detached retina. History of uncomplicated surgery within the eyeball or around the study eye, except lid surgery. Absence of lens in study eye. Uncontrolled hypertension, defined as systolic blood pressure (BP) >180 mmHg or diastolic BP >100 mmHg under appropriate antihypertensive treatment. Hypersensitivity to aflibercept or medications used in the study (fluorescein, mydriatic eye drops, etc.). Pregnancy or lactation at Screening or at baseline for women of child-bearing potential. History of blood clotting events. History or evidence of cardiac conditions, or inability to perform any physical activity without discomfort; ventricular arrhythmia; and atrial fibrillation. History of laser therapy in the macular region. Any prior or current treatment with corticosteroids inside or immediately around the study eye. Any prior or current treatment involving the macula with photodynamic therapy (PDT) with verteporfin, transpupillary thermotherapy, radiation therapy, or retinal laser treatment in the study eye. Any prior or current treatment with panretinal photocoagulation. Any prior or current treatment with ethambutol; deferoxamine and topiramate; tamoxifen, hydroxychloroquine, chloroquine, or vigabatrin; and amiodarone. Any investigational product for the treatment of eye conditions and systemic conditions, 30 days or 5 half-lives (whichever is longer), prior to randomization, and throughout the study, except dietary supplements or vitamins.
Study: A 3-month Study to Assess the Safety of ONS-5010 in Subjects With Visual Impairment Due to Retinal Disorders
Clinicaltrials.gov Identifier: NCT04516278
Sponsor: Outlook Therapeutics, Inc.
Purpose: The study will evaluate the safety of ophthalmic bevacizumab in subjects diagnosed with a retinal condition that would benefit from treatment with intravitreal injection of bevacizumab, including: exudative age-related macular degeneration, diabetic macular edema, or branch retinal vein occlusion.
Design: Single group, no masking
Number of Patients: 180
Inclusion Criteria: Active clinical diagnosis and OCT confirmation of one of the following retinal disorders: exudative age-related macular degeneration (AMD), diabetic macular edema (DME), or branch retinal vein occlusion (BRVO) and, in the opinion of the Investigator, requires treatment with an anti-VEGF therapy.
Exclusion Criteria: Previous use of approved anti-VEGF or Avastin® within 4 weeks preceding randomization. Macular edema due to something other than exudative AMD, DME or BRVO, in the study eye. History of inadequate response to previous intravitreal anti-VEGF therapy. History of any intraocular or periocular corticosteroid injection or implant, in the study eye. Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within 1-month preceding randomization. Any concurrent intraocular condition in the study eye that may require medical or surgical intervention or contribute to vision loss during the study period. Active intraocular inflammation in the study eye. Current vitreous hemorrhage in the study eye. Polypoidal choroidal vasculopathy (PCV) in the study eye. History of idiopathic, infectious or autoimmune-associated uveitis in either eye. Current ocular or periocular infection, such as conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye. Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥30 mmHg despite treatment with anti-glaucoma medication). Premenopausal women not using adequate contraception. Current treatment for active systemic infection. Known allergy to any component of the study drug, not amenable to treatment.
Information: jenniferkissner@outlooktherapeutics.com
Study: A Study to Test Different Doses of BI 836880 in Patients With an Eye Disease Called Wet Age-related Macular Degeneration (wAMD)
Clinicaltrials.gov Identifier: NCT03861234
Sponsor: Boehringer Ingelheim
Purpose: The main objective is to investigate ocular and systemic safety and tolerability as well as disease improvement of BI 836880 after a single Intravitreal (IVT) injection and after multiple IVT injections of several doses.
Design: Single group, no masking
Number of Patients: 42
Inclusion Criteria: Men and women over the age of 55 with active choroidal neovascularisation (CNV) secondary to Age-related macular degeneration (AMD) despite anti-vascular endothelial growth factor (VEGF) therapies (at least 3 prior injections with the last injection within 12 to 4 weeks before screening). Active CNV secondary to AMD is to be defined either by recent fluorescein or OCT angiogram within 4 weeks prior to screening or fluorescein or Optical coherence tomography (OCT) angiogram obtained prior to first anti VEGF-treatment to confirm the diagnosis and still active according to investigator judgement. For multiple rising dose (MRD) part only: No more than 18 months elapsed since the first anti-VEGF therapy in the study eye. For MRD part only: Central subfield retinal thickness >350 microns in the study eye on Heidelberg Spectralis Spectral Domain Optical Coherence Tomography (SD-OCT). Presence of sub- and/or intraretinal fluid on SD-OCT in the study eye. Any active CNV with subfoveal leakage in the study eye as determined by OCT. No subretinal hemorrhage involving the fovea in the study eye No significant subfoveal fibrosis or atrophy on SD-OCT in the study eye that, in the opinion of the investigator, is able to prevent improvement in Best Corrected Visual Acuity (BCVA) and/or Central Subfield Thickness (CSFT). Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity (VA) in the study eye between 70 and 24 letters inclusive (approximately 20/40 and 20/320 or 6/12 and 6/95) at screening. Best-corrected VA in the non-study eye better than best-corrected VA in the study-eye. If both eyes are eligible and have identical VA the investigator may select the study eye. Female subjects must be of non-childbearing potential. Signed informed consent consistent with ICH GCP guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions. Not under any administrative or legal supervision or under institutionalization due to regulatory or juridical order.
Exclusion Criteria: Additional eye disease in the study eye that could compromise best corrected Visual Acuity (VA)(BCVA) with visual field loss, uncontrolled glaucoma (Intra-Ocular Pressure (IOP)>24), clinically significant diabetic maculopathy, history of ischemic optic neuropathy or retinal vascular occlusion, symptomatic vitreomacular traction, or genetic disorders such as retinitis pigmentosa); history of high myopia > 8 diopters in the study eye. Anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation with Spectral Domain Optical Coherence Tomography (SD-OCT). Any prior intraocular surgery in the study eye other than uneventful lens replacement for cataract within 3 months prior to screening. Aphakia or total absence of the posterior capsule. Yttrium aluminum garnet (YAG) laser capsulotomy permitted, more than 3 month prior to enrollment in the study eye. Current or planned use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol). Medical history or condition: Uncontrolled diabetes mellitus, with hemoglobin A1c (HbA1c) >10%, myocardial infarction or stroke within 12 months of screening, active bleeding disorder, concomitant use of warfarin or anticoagulation therapy (use of antiplatelet therapy such as aspirin is allowed), major surgery within 1 month of screening or when planned within the study period, hepatic impairment, uncontrolled hypertension. Patients with a clinically relevant abnormal screening hematology, blood chemistry, or urinalysis, if the abnormality defines a significant disease as defined in other exclusion criteria. AST or ALT greater than 2.0-fold the upper limit of normal at screening. Patients with total bilirubin 2.5x upper limit of normal at screening. Patient with impaired renal function defined as calculated GFR< 30 mL/min. Significant alcohol or drug abuse within past 2 years per investigator judgement. Previous participation in this trial or in other trials with Intravitreal (IVT) injections or in trials for treatment of Wet Age-related Macular Degeneration (wAMD). Significant disease or other medical conditions (as determined by medical history, examination and clinical investigations at screening) that may, in the opinion of the investigator result in the any of the following: Put the patient at risk because of participation in the study, Influence the results of the study, Cause concern regarding the patient's ability to participate in the study. Known hypersensitivity to fluorescein or any of the ingredients used in the Investigational Medicinal Product (IMP) formulation, or any of the medications used. Active intraocular inflammation in the study eye. Active infectious conjunctivitis in either eye.
Information: clintriage.rdg@boehringer-ingelheim.com
Study: MMP-9 Inhibition for Recalcitrant Wet AMD
Clinicaltrials.gov Identifier: NCT04504123
Sponsor: University of Iowa
Purpose: The investigators plan to evaluate the effect of oral doxycycline versus placebo on the anatomic and functional outcomes in persistent sub-retinal eye fluid in neovascular wet age-related macular degeneration. This subset are incomplete or non-responders to current anti-VEGF intravitreal therapy.
Design: Randomized, parallel assignment
Number of Patients: 50
Inclusion Criteria: Wet age-related macular degeneration (wAMD). Solely treated with anti-VEGF IVI for active CNV due to wAMD. However, enrolled patients can have other retinal pathologies such as diabetic retinopathy or vein occlusion for which they are not being treated with anti-VEGF IVI; Must have persistent sub-retinal with or without intra-retinal fluid due to active CNV from wAMD and must have been switched only once to a different anti-VEGF agent and subsequently received a maximum of 4 IVI (with the second agent) over a period of 7 months prior to being enrolled; Must have been treated with anti-VEGF IVI for active CNV from wAMD for a total period of one year or less prior to enrollment; Must not have encountered previous side effects from tetracycline medications.
Exclusion Criteria: Ocular: History of uveitis (including endophthalmitis) or presence of intraocular inflammation; Presence of significant epiretinal membrane or macular hole causing distortion of macular anatomy; Presence of media opacity preventing discerning of fluid on OCT; Any prior ophthalmic surgery (including YAG or retinal laser) within the previous 6 months or anticipated need for any ophthalmic surgery (including cataract extraction) for 9 months following randomization; History of peribulbar corticosteroid injection to the studied eye or the fellow eye within the past 6 months; History of intravitreal triamcinolone acetonide injection to the studied eye within the past 4 months; An ocular condition (other than AMD) is present in the studied eye that, in the opinion of the investigator, might alter visual acuity during the course of the study (e.g., retinal vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, and Irvine-Gass syndrome); CNV due to causes other than wAMD; Inability to follow up at the 6th and 9th month time points after recruitment; Missing two or more consecutive injections during the six months treatment period; Patient requiring imminent need for IVI anti-VEGF medication switch or another treatment intervention, such as photodynamic therapy, during the 9 months trial period. Diagnosed with active CNV due to AMD and who have been receiving anti-VEGF IVI for longer than 1 year. Systemic: Patient with and/or who developed an unstable medical status (e.g., glycemic control, blood pressure, cardiovascular disease, individuals who are unlikely or unable to complete the 9 months trial period) in the opinion of the investigator; Significant renal disease (defined as a serum creatinine >2.5 mg/dL); Systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg; History of headaches associated with tetracycline therapy; History of pseudotumor cerebri; History of tetracycline therapy within the past 6 months; Pregnancy or patient intending to become pregnant within the 9 months of the trial period. For women of child-bearing potential, a pregnancy test will be performed; Sexually active women of child-bearing potential not actively practicing birth control by using a medically accepted device or therapy (i.e., intrauterine device, hormonal contraceptive, or barrier device) during the study period (at least 24 months). This is important as doxycycline may interfere with the effectiveness of hormonal contraceptives. Hence, sexually active women of child-bearing potential who use a hormonal contraceptive will be required to use a second form of contraception to safeguard against contraceptive failure while participating in the study; Known allergy/intolerance to doxycycline, tetracyclines, or any ingredient in the study drug or placebo; Patients receiving phenytoin, barbiturates, carbamazepine, digoxin, or isotretinoin; patients with gastroparesis; patients with a history of gastrectomy, gastric bypass surgery, or otherwise deemed achlorhydric should all be excluded due to altered doxycycline pharmacokinetics and/or bioavailability; Patients taking strontium, acitretin, or tretinoin should excluded due to te potential for serious interactions with doxycycline; Patients with abnormal ALT or AST at baseline will be referred to their primary care physician for medical clearance for participation in this study.
Information: elliott-sohn@uiowa.edu
Study: A Study to Understand Effectiveness and Safety of ABP 938 Compared to Aflibercept (Eylea) in Patients Suffering With Neovascular Age-related Macular Degeneration [Neovascular (Wet) AMD]
Clinicaltrials.gov Identifier: NCT04270747
Sponsor: Amgen
Purpose: The purpose of this study is to compare the efficacy and safety of ABP 938 versus Aflibercept (Eylea) in the treatment of neovascular age-related macular degeneration. Subjects will be randomized in a masked 1:1 ratio to receive 2 mg (0.05 mL) of either ABP 938 (Treatment Group A) or aflibercept (Treatment Group B) administered by intravitreal (IVT) injection.
Design: Randomized, parallel assignment, triple masking
Number of Patients: 566
Inclusion Criteria: Subjects must sign an Institutional Review Board/Independent Ethics Committee approved informed consent form before any study-specific procedures. Men or women ≥50 years old. Subjects must be diagnosed with neovascular (wet) AMD in the study eye. Active treatment naïve CNV lesions secondary to neovascular (wet) AMD as confirmed with SD OCT, FA and Fundus Photography (FP) in the study eye. BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing. Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active CNV in the study eye. Central retinal thickness of ≥300 µm in the study eye as determined by SD-OCT at screening.
Exclusion Criteria: Subjects are excluded if they meet any of the following criteria in the study eye: Total lesion size >9 disc areas (22.86mm2, including blood, scars, and neovascularization) in the study eye; Active CNV area (classic plus occult components) that is < 50% of the total lesion area in the study eye; Scar, fibrosis, or atrophy involving the center of the fovea in the study eye; Presence of retinal pigment epithelium tears or rips involving the macula in the study eye; History of any vitreous hemorrhage within 4 weeks before randomization in the study eye; Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye; Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation) in the study eye; History of retinal detachment in the study eye; Any history of macular hole of stage 2 and above in the study eye; Any macular pathology that might limit vision i.e., Vitreomacular traction or significant epiretinal membrane; Any intraocular or periocular surgery within 3 months before randomization on the study eye, except lid surgery, which may not have taken place within 4 weeks before randomization, as long as it is unlikely to interfere with the injection; Prior trabeculectomy or other filtration surgery in the study eye; Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye; Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye; Previous therapeutic radiation in the region of the study eye; History of corneal transplant or corneal dystrophy in the study eye; Significant media opacities, including cataract, which might interfere with visual acuity or assessment of safety, in the study eye; Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye that, in the opinion of the investigator, requires planned medical or surgical intervention during the study or increases the risk to the subject beyond what is expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety. Subjects are excluded if they meet any of the following criteria in either eye: History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina, other than neovascular (wet) AMD; Active intraocular inflammation or active or suspected ocular or periocular infection, within 2 weeks before randomization; Active scleritis or episcleritis or presence of scleromalacia.
Information: medinfo@amgen.com
Study: RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Neovascular Age-Related Macular Degeneration (nAMD) (AAVIATE)
Clinicaltrials.gov Identifier: NCT04514653
Sponsor: Regenxbio Inc.
Purpose: RGX-314 is being developed as a novel one-time gene therapy treatment for the treatment of neovascular (wet) age related macular degeneration (wet AMD).
Design: Randomized, sequential assignment, no masking
Number of Patients: 40
Inclusion Criteria: Age ≥50 and ≤89. Diagnosis of subfoveal CNV secondary to age-related macular degeneration in the study eye. Participants must have demonstrated a meaningful response to anti-VEGF therapy. Willing and able to provide written, signed informed consent for this study.
Exclusion Criteria: CNV or macular edema in the study eye secondary to any causes other than AMD. Subfoveal fibrosis or atrophy in study eye. Participants who have had a prior vitrectomy. Any condition in the investigator's opinion that could limit VA improvement in the study eye. Active or history of retinal detachment in the study eye. Uncontrolled glaucoma in the study eye. Received any gene therapy. Any condition preventing visualization of the fundus or VA improvement in the study eye, eg, cataract, vitreous opacity, fibrosis, atrophy, or retinal epithelial tear in the center of the fovea. History of intraocular surgery in the study eye. Receipt of any investigational product within 30 days of Visit 2. Myocardial infarction, cerebrovascular accident, or transient ischemic attacks within 6 months of study entry.
Information: patientadvocacy@regenxbio.com
Study: A Study to Compare SB15 (Proposed Aflibercept Biosimilar) to Eylea in Subjects With Neovascular Age-related Macular Degeneration (AMD)
Clinicaltrials.gov Identifier: NCT04450329
Sponsor: Samsung Bioepis Co., Ltd.
Purpose: This is a randomised, double-masked, parallel group, multicentre study to evaluate the efficacy, safety, PK, and immunogenicity of SB15 compared to Eylea in subjects with neovascular AMD.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 100
Inclusion Criteria: Age ≥50 years at screening. Treatment naïve, *active subfoveal choroidal neovascularization (CNV) lesion secondary to AMD in the study eye. The area of CNV must occupy at least 50% of total lesion in the study eye. Total lesion area ≤ 9.0 Disc Areas (DA) in size (including blood, scars, and neovascularization) in the study eye. BCVA of 20/40 to 20/200 (letter score of 73 to 34, inclusive) using ETDRS charts or 2702 series Number charts in the study eye at Screening and at Week 0 (day 1) prior to randomization. Nonchildbearing potential female, OR childbearing potential female subjects or male subjects with their (respectively male or female) partners who agree to use at least two forms of appropriate contraception method that can achieve a failure rate of less than 1% per year from Screening until 3 months after the last IVT injection of IP. Written informed consent form (ICF) must be obtained from the subject prior to any study related procedure. Willingness and ability to undertake all scheduled visits and assessments.
Exclusion Criteria: Study eye: Sub- or intra-retinal hemorrhage that comprises more than 50% of the entire lesion or presence of blood with the size of 1 DA or more involving the center of fovea. Study eye: Scar, fibrosis, or atrophy involving the center of the fovea. Study eye: Presence of CNV due to other causes, such as ocular histoplasmosis, trauma, multifocal choroiditis, angioid streaks, history of choroidal rupture, or pathologic myopia. Study eye: Presence of retinal pigment epithelial tears or rips involving the macula. Study eye: Presence of macular hole at any stage. Study eye: Any concurrent macular abnormality other than AMD which could affect central vision or the efficacy of IP. Study eye: Any concurrent ocular condition which, in the opinion of the Investigator, could either confound the interpretation of efficacy and safety of IP or require medical or surgical intervention during the study period. Either eye: History or clinical evidence of diabetic retinopathy (except for mild non-proliferative diabetic retinopathy) or diabetic macular edema (DME). Study eye: Current vitreous hemorrhage. Either eye: Any previous IVT anti-vascular endothelial growth factor (VEGF) treatment. Any previous systemic anti-VEGF treatment. Study eye: History of treatment involving macula such as macular laser photocoagulation, photodynamic therapy (PDT), transpupillary thermotherapy (TTT), radiation therapy, or any ocular treatment for neovascular AMD. Any systemic treatment or therapy (including prescribed herbal medication) to treat neovascular AMD within 30 days prior to randomization. However, dietary supplements, vitamins, or minerals will be allowed. Study eye: History of vitrectomy, scleral buckling (encircling), glaucoma filtration surgery, corneal transplantation, or panretinal photocoagulation. Study eye: Previous ocular (intraocular and peribulbar) corticosteroids injection/implant within 1 year prior to randomization. Study eye: Topical ocular corticosteroids administered for ≥ 30 consecutive days or for ≥ 60 nonconsecutive days within 90 days prior to randomization. Use of systemic corticosteroids for 30 or more consecutive days within 90 days prior to randomization (inhaled steroid is permitted). Study eye: Any other intraocular surgery or periocular surgery within 90 days prior to randomization, except for lid surgery, which may not have taken place within 30 days prior to randomization. Current use of medications known to be toxic to the lens, retina, or optic nerve at Screening. Study eye: Previous radiation therapy near the region of the study eye. Previous participation in clinical studies with IP to treat neovascular AMD in either eye. Previous participation in clinical studies with IP to treat disease other than neovascular AMD within 90 days prior to randomization (excluding dietary supplementary, vitamins, and minerals). Subject with only one functional eye (defined as BCVA of counting finger or less on the eye with worse vision). Study eye: Spherical equivalent of the refractive error demonstrating more than 6 diopters of myopia. For subjects who have undergone previous refractive or cataract surgery in the study eye, the preoperative refractive error in the study eye cannot exceed 6 diopters of myopia. Study eye: Aphakia or absence of the posterior capsule (unless it occurred as a result of a YAG laser posterior capsulotomy in association with prior posterior chamber IOL implantation). Either eye: Active or suspected ocular and periocular infection at Screening or at randomization. Either eye: Active intraocular inflammation including scleritis at Screening or at randomization. Either eye: History of idiopathic or autoimmune-associated uveitis. Study eye: Uncontrolled ocular hypertension (defined as intraocular pressure [IOP] ≥25 mmHg despite treatment with anti-glaucoma medication) at screening. Known allergic reactions and/or hypersensitivity to any component of Eylea or SB15. History of allergy to the fluorescein sodium for injection in angiography History of a medical condition that would preclude scheduled study visits or safe use of IP in the opinion of the Investigator. Uncontrolled systemic disease including but not limited to uncontrolled diabetes mellitus (in the opinion of the Investigator), uncontrolled systemic hypertension (systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 100 mmHg on optimal medical regimen), or uncontrolled atrial fibrillation (resting heart rate ≥ 110 beats per minutes) at screening. Stroke, transient ischemic attacks, or myocardial infarction within 180 days prior to randomization. History of recurrent significant infections and/or current treatment for systemic infection. Severe renal impairment with dialysis or a history of renal transplant. Malignancy (other than non-melanoma skin cancer) under treatment or with history of metastatic disease. Women of childbearing potential who are pregnant, planning to become pregnant, lactating, or not using adequate birth control, as specified in protocol. For women of childbearing potential, a serum pregnancy test must result negative at screening. Employees of investigational sites, individuals directly involved with the conduct of the study.
Information: sbregistry@samsung.com
Study: Safety, Tolerability, and Efficacy of Aflibercept in Patients With Neovascular Age-Related Macular Degeneration (CANDELA)
Clinicaltrials.gov Identifier: NCT04126317
Sponsor: Regeneron Pharmaceuticals
Purpose: The primary objectives of the study are to determine the safety of high-dose aflibercept (hereafter referred to as HD) and to determine if HD provides greater intraocular pharmacodynamic (PD) effect and/or longer duration of action compared to intravitreal aflibercept injection (hereafter referred to as IAI).
Design: Randomized, parallel assignment, single masking
Number of Patients: 100
Inclusion Criteria: Men or women ≥50 years of age with active subfoveal choroidal neovascularization (CNV) secondary to nAMD. Best Corrected Visual Acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 78 to 24 (Snellen equivalent of 20/32 to 20/320) in the study eye.
Exclusion Criteria: Evidence of CNV due to any cause other than nAMD in either eye. Evidence of diabetic macular edema (DME) or diabetic retinopathy (defined as more than 1 microaneurysm) in either eye in diabetic patients. Prior use of IVT anti-VEGF agents (aflibercept, ranibizumab, bevacizumab, brolucizumab, pegaptanib sodium) in the study eye. Prior IVT investigational agents in either eye (eg, anti-ang-2/anti-VEGF bispecific monoclonal antibodies, gene therapy). Previous use of intraocular or periocular corticosteroids within 120 days of screening or treatment with an IVT steroid implant at any time in the study eye. History of vitreoretinal surgery (including scleral buckling) in the study eye. Any other intraocular surgery within 12 weeks (84 days) before the screening visit. History of corneal transplant or corneal dystrophy in study eye. NOTE: Other protocol defined inclusion/exclusion criteria apply.
Information: clinicaltrials@regeneron.com
Study: Study to Gather Information on Safety and Use of High Dose Aflibercept Injection Into the Eye in Patients With an Age Related Eye Disorder That Causes Blurred Vision or a Blind Spot Due to Abnormal Blood Vessels That Leak Fluid Into the Light Sensitive Lining Inside the Eye (PULSAR)
Clinicaltrials.gov Identifier: NCT04423718
Sponsor: Bayer
Purpose: In this study researchers want to learn more about changes in visual acuity (clarity of vision) with a high dose treatment with Aflibercept (Eylea) in patients suffering from neovascular age-related macular degeneration (nAMD). Neovascular AMD is an eye disease that causes blurred vision or a blind spot due to abnormal blood vessels that leak fluid or blood into the light sensitive lining inside the eye (retina). The fluid buildup causes the central part of the retina (macula) responsible for sharp, straight-ahead vision to swell and thicken (edema), which distorts vision.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 960
Inclusion Criteria: Active subfoveal CNV secondary to nAMD, including juxtafoveal lesions that affect the fovea as assessed in the study eye. Total area of CNV (including both classic and occult components) must comprise greater than 50% of the total lesion area in the study eye. BCVA ETDRS letter score of 78 to 24 (corresponding to a Snellen equivalent of approximately 20/32 to 20/320) in the study eye. Decrease in BCVA determined to be primarily the result of nAMD in the study eye. Presence of IRF and/or SRF affecting the central subfield of the study eye on OCT. Contraceptive use by men or women should be consistent with local regulations regarding the methods of highly effective contraception for those participating in clinical studies. Other protocol-specified inclusion criteria.
Exclusion Criteria: Causes of CNV other than nAMD in the study eye. Scar, fibrosis, or atrophy involving the central subfield in the study eye. Presence of retinal pigment epithelial tears or rips involving the central subfield in the study eye. Uncontrolled glaucoma (defined as IOP >25 mmHg despite treatment with anti-glaucoma medication) in the study eye. History of idiopathic or autoimmune uveitis in the study eye. Myopia of a spherical equivalent of at least 8 diopters in the study eye prior to any refractive or cataract surgery. History or clinical evidence of diabetic retinopathy, diabetic macular edema, or any retinal vascular disease other than nAMD in either eye. Evidence of extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in either eye at the time of screening/randomization. Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg). Any prior or concomitant ocular (in the study eye) or systemic treatment (with an investigational or approved, anti-VEGF or other agent) or surgery for nAMD, except dietary supplements or vitamins. Other protocol-specified exclusion criteria.
Information: clinical-trials-contact@bayer.com
A Study to Assess the Efficacy and Safety of AKST4290 With Aflibercept in Patients With Newly Diagnosed nAMD (PHTHALO-205)
Clinicaltrials.gov Identifier: NCT04331730
Sponsor: Alkahest, Inc.
Purpose: This study will evaluate the efficacy and safety of AKST4290 in combination with aflibercept injections in subjects with newly diagnosed neovascular age-related macular degeneration (nAMD).
Design: Randomized, parallel assignment, double masking
Number of Patients: 100
Inclusion Criteria: Men and women with newly diagnosed active CNV secondary to AMD, diagnosed by a retinal specialist with all the following characteristics and ophthalmic inclusion criteria applied to the study eye, as assessed by a central reader: Has been examined by a retinal specialist and found to be eligible to receive Intravitreal Aflibercept Injection (IAI) in the study eye. No prior treatment for nAMD in the study eye. Study eye has not undergone pars plana vitrectomy or glaucoma filtering surgery. Participation in studies of investigational drugs must have been discontinued within 30 days or 5 half-lives of the drug (whichever was longer) prior to screening. CST thickness ≥ 250 microns on SD-OCT (exclusive of subretinal pigment epithelial fluid, inclusive of SRF). Presence of SRF and/or IRF on SD-OCT. Total lesion size not greater than 12 disc areas (30.48 mm2) (1 disc area = 2.54 mm2) on FA. If present, subretinal hemorrhage must comprise < 50% of the total lesion area on FA, SD-OCT, or FP/FAF. No subfoveal fibrosis or atrophy on FA, SD-OCT, or FP/FAF. Active CNV membranes with subfoveal leakage or juxtafoveal leakage too close for laser photocoagulation. BCVA in the study eye between 70 and 24 letters inclusive. Body mass index (BMI) between (and inclusive of) 18 and 40 at screening.
Exclusion Criteria: Participation in studies of investigational drugs within 30 days or 5 half-lives of the drug (whichever was longer) prior to screening. Known hypersensitivity to the active substance or any of the excipients of AKST4290 or aflibercept. Active or suspected ocular or periocular infection and/or active, severe intraocular inflammation. Any form of macular degeneration that is not age-related (e.g., Best's disease, Stargardt's disease, Sorsby's disease). Additional disease in the study eye that could compromise BCVA (i.e., uncontrolled glaucoma (IOP >24) with visual field loss, clinically significant diabetic macular edema, history of ischemic optic neuropathy or retinal vascular occlusion, vitreomacular traction, high myopia > 6 diopters, or genetic disorders such as retinitis pigmentosa). Presence of RPE tears or rips in the study eye. Anterior segment and vitreous abnormalities in the study eye that would preclude adequate visualization with FP/FAF, FA, or SD-OCT. Intraocular surgery in the study eye within 3 months prior to screening. Aphakia or total absence of the posterior capsule (yttrium aluminum garnet [YAG] laser capsulotomy permitted in an eye with a posterior chamber intraocular lens if performed a minimum of 1 month prior to enrollment) in the study eye. Known allergy to fluorescein sodium. Significant alcohol or drug abuse within past 2 years. Based on ECG reading, subjects with a risk of QT prolongation. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Information: trials@alkahest.com
Study: A Phase 2 Study of RBM-007 Alone and RBM-007 With Eylea in Subjects With Wet Age-related Macular Degeneration (TOFU)
Clinicaltrials.gov Identifier: NCT04200248
Sponsor: Ribomic USA Inc
Purpose: This is a multicenter, active-controlled, double masked study assessing the safety, efficacy and durability of four monthly intravitreal (IVT) injections of RBM-007 monotherapy, and four monthly RBM-007 injections in combination with Eylea dosed at every other month, compared to Eylea monotherapy dosed at every other month in approximately eighty-one subjects with exudative age-related macular degeneration (AMD).
Design: Randomized, parallel assignment, double masking
Number of Patients: 81
Inclusion Criteria: Provide signed written informed consent. Male or female 55 years of age or older on the date of signing the consent and able and willing to comply with all treatment and study procedures. Diagnosis of exudative age-related macular degeneration in the study eye, for which previous standard treatment with intravitreal anti-vascular endothelial growth factor agents (at least 4 injections over the past 8 months) has demonstrated incomplete resolution of exudation, as assessed by spectral domain optical coherence tomography. Presence of macular edema or subretinal fluid. Absence of central atrophy or retinal epithelial tear in the fovea or any condition preventing visual acuity improvement in the study eye. Visual acuity of 78 to 24 letters (20/32 to 20/320) in the study eye. Visual acuity of 24 letters (20/320) or better in the fellow eye. Reasonably clear media and some fixation in the study eye to allow for good quality tomography and fundus photography.
Exclusion Criteria: Use of any of the following treatments or anticipated use of any of the following treatments to the study eye: Any intravitreal treatment within 4 weeks prior to Baseline (visit 1). Intravitreal or periocular corticosteroid, within 90 days prior to visit 1 (day 1) and throughout the study. Fluocinolone acetonide intravitreal implant, within 12 months prior to visit 1 (day 1) and throughout the study. Visudyne photodynamic therapy, within 90 days prior to visit 1 (day 1) and throughout the study. Uncontrolled or advanced glaucoma, evidenced by an intraocular pressure of >21 mmHg or cup/disc ratio > 0.8 while on medical therapy, or chronic hypotony (<6 mmHg) in the study eye. Evidence of any other ocular disease other than wet age-related macular degeneration in the study eye that may confound the outcome of the study History of vitrectomy in the study eye. Need for ocular surgery in the study eye during the course of the study. YAG laser capsulotomy within 30 days prior to visit 1 (day 1) in the study eye. Intraocular surgery, including lens removal or laser, within 90 days prior to visit 1 (day 1) in the study eye.
Information: yusuf.ali@ribomic.com; daniel.pereira@ribomic.com
Study: A Study to Evaluate the Efficacy and Safety of KSI-301, an Anti-VEGF Antibody Biopolymer Conjugate, Versus Aflibercept in Patients with Neovascular (Wet) Age-Related Macular Degeneration (DAZZLE)
Clinicaltrials.gov Identifier: NCT04049266
Sponsor: Kodiak Sciences Inc
Purpose: This study will evaluate the efficacy, safety, durability, and pharmacokinetics of KSI-301 administered at 12, 16 and 20 weeks intervals as specified in the protocol, compared with aflibercept once every 8 weeks (Q8W), in participants with treatment-naïve neovascular (wet) age-related macular degeneration (nAMD).
Design: Randomized, parallel assignment
Number of Patients: 368
Inclusion Criteria: Signed informed consent prior to participation in the study. Active, treatment-naïve choroidal neovascularization (CNV) secondary to AMD. BCVA ETDRS score between 80 and 25 letters (Snellen equivalent of 20/25 to 20/320), inclusive. Other protocol-specified inclusion criteria may apply.
Exclusion Criteria: CNV secondary to other causes in the Study Eye. Any history of macular pathology unrelated to AMD but affecting vision or contributing to subretinal or intraretinal fluid. Any history or evidence of a concurrent intraocular condition in the Study Eye that, in the judgment of the Investigator, could require either medical or surgical intervention during the study to prevent or treat visual loss. Active ocular or periocular infection or inflammation. Prior administration of any approved or investigational treatment for neovascular AMD in the Study Eye. Uncontrolled glaucoma in the Study Eye. Women who are pregnant or lactating or intending to become pregnant during the study. Stroke or myocardial infarction in the 6-month period prior to day 1. Uncontrolled blood pressure defined as a systolic value >180 mmHg or diastolic value ≥100 mmHg while at rest. History of a medical condition that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product. Other protocol-specified exclusion criteria may apply.
Information: KSI-CL-102@kodiak.com
Study: A Study Assessing AR-13503 Implant Alone and in Combination with Aflibercept in Subjects With nAMD or DME
Clinicaltrials.gov Identifier: NCT03835884
Sponsor: Aerie Pharmaceuticals
Purpose: First-in-human study of the safety of AR-13503 sustained release intravitreal implant in subjects with neovascular age-related macular degeneration (nAMD) and subjects with diabetic macular edema (DME).
Design: Randomized, sequential assignment, single
Number of Patients: 102
Inclusion Criteria: Inclusion Criteria for Subjects with Neovascular Age-Related Macular Degeneration (nAMD) or Diabetic Macular Edema (DME): 50 years of age or older. Presence of active subfoveal or juxtafoveal Choroidal Neovascularization (CNV) (any subtype) with leakage affecting the fovea secondary to Age-Related Macular Degeneration (AMD). Best Corrected Visual Acuity (BCVA) in the study eye at Baseline (day 0): Stage 1: between 65 and 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/50 and 20/640 Snellen equivalent) Stage 2: between 65 and 20 ETDRS letters (20/50 and 20/400 Snellen equivalent). Able and willing to give signed informed consent and follow study instructions. Inclusion Criteria for Subjects with DME: Subjects with Diabetic Macular Edema (DME) must meet all the following criteria to enter into the Study: 18 years of age or older. Type 1 or 2 diabetes mellitus with center-involved DME. BCVA in the study eye at Baseline (day 0): Stage 1: between 65 and 10 ETDRS letters (20/50 and 20/640 Snellen equivalent) Stage 2: between 65 and 20 ETDRS letters (20/50 and 20/400 Snellen equivalent). Able and willing to give signed informed consent and follow study instructions.
Exclusion Criteria: Exclusion Criteria for Subjects with Neovascular Age-Related Macular Degeneration (nAMD): Ophthalmic: Use of intravitreal aflibercept within 8 weeks, ranibizumab or bevacizumab within 6 weeks. History of vitreoretinal surgery in the study eye. Any ocular disease in the study eye that in the Investigator and Reading Center's opinion may confound assessment of the macula, affect central vision, confound results, or preclude improvement in visual acuity. Any current or history of periocular or intraocular inflammation or evidence of infection in either eye. Media clarity insufficient to obtain quality fundus and OCT images in the study eye. Systemic: History or current systemic condition that in the Investigator opinion preclude the safe administration of the study treatment or confound results. History of allergy or sensitivity to fluorescein or povidone iodine. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. Participation in an investigational study within 30 days of Screening. Exclusion Criteria for Subjects with DME: Ophthalmic: Use of intraocular or periocular corticosteroids within 6 months, aflibercept within 8 weeks, ranibizumab or bevacizumab within 6 weeks. History of vitreoretinal surgery in the study eye. High risk proliferative diabetic retinopathy in the study eye and related complications. Structural damage to the center or the macula that is likely to preclude improvement in visual acuity in the study eye after resolution of the DME. Media clarity insufficient to obtain quality fundus and OCT images in the study eye. Systemic: History or current medical condition that in the Investigator's opinion preclude the safe administration of the study treatment or confound results. History of allergy or sensitivity to fluorescein or povidone iodine. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. Participation in an investigational study within 30 days of Screening.
Information: nramirez@aeriepharma.com, pbraswell@aeriepharma.com
Study: A Depot Formulation of Sunitinib Malate (GB-102) Compared to Aflibercept in Subjects with Wet AMD (ALTISSIMO)
Clinicaltrials.gov Identifier: NCT03953079
Sponsor: Graybug Vision
Purpose: Phase 2b, multicenter, visual examiner-masked, randomized active-controlled, parallel-arm design study to evaluate the safety and duration of repeated IVT injections of 3 dose levels of GB‑102 compared with aflibercept.
Design: Randomized, parallel assignment, single masking
Number of Patients: 220
Inclusion Criteria: Males or females ≥50 years of age. Presence of a CNV lesion secondary to AMD treated with at least 3 prior IVT injections of an anti-VEGF agent (aflibercept, bevacizumab, or ranibizumab). Demonstrated response to prior anti-VEGF treatment since diagnosis. BCVA of 35 letters or better.
Exclusion Criteria: History, within 6 months prior to screening, of any of the following: myocardial infarction, any cardiac event requiring hospitalization, treatment for acute congestive heart failure, transient ischemic attack, or stroke. Uncontrolled hypertension, diabetes mellitus or IOP. Chronic renal disease. Abnormal liver function. Women who are pregnant or lactating.
Information: vsmith@graybug.com
Study: Study to Assess the Efficacy and Safety of Brolucizumab 6mg Compared to Aflibercept 2 mg in a Treat-to-control Regimen (TALON)
Clinicaltrials.gov Identifier: NCT04005352
Sponsor: Novartis Pharmaceuticals
Purpose: The study is a 64-week randomized, double-masked, multi-center, active-controlled, two-arm study in patients with nAMD (neovascular age related macular degeneration) who have not previously received anti-VEGF (vascular endothelial growth factor) treatment. Patients who consent will undergo screening assessments to evaluate their eligibility based on the inclusion and exclusion criteria.
Design: Randomized, parallel assignment, triple masking
Number of Patients: 692
Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Male or female patients ≥50 years of age at screening who are treatment naïve. Active choroidal neovascularization (CNV) secondary to AMD that affects the central subfield, including retinal angiomatous proliferation (RAP) with a CNV component, confirmed by presence of active leakage from CNV seen by fluorescein angiography and sequelae of CNV, eg pigment epithelial detachment (PED), subretinal or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema (study eye). Presence of intraretinal fluid (IRF) or subretinal fluid (SRF) that affects the central subfield, as seen by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye). Best-corrected visual acuity (BCVA) score between 83 and 38 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at both screening and baseline visit (study eye).
Exclusion Criteria: Ocular conditions/disorders at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require planned medical or surgical intervention during the first 12-month study period, structural damage of the fovea, atrophy or fibrosis at the center of the fovea (study eye). Any active intraocular or periocular infection or active intraocular inflammation, at screening or baseline (study eye). Uncontrolled glaucoma defined as intraocular pressure (IOP) >25 mmHg on medication, or according to investigator's judgment, at screening or baseline (study eye). Ocular treatments: previous treatment with any anti-vascular endothelial growth factor (VEGF) drugs or investigational drugs, intraocular or periocular steroids, macular laser photocoagulation, photodynamic therapy, vitreoretinal surgery, intraocular surgery (study eye). Stroke or myocardial infarction during the 6-month period prior to baseline. Systemic anti-VEGF therapy at any time.
Information: novartis.email@novartis.com
Study: A Clinical Effectiveness Study Examining the Efficacy and Safety of ONS-5010 in Subjects with Neovascular Age-related Macular Degeneration (AMD)
Clinicaltrials.gov Identifier: NCT03834753
Sponsor: Outlook Therapeutics, Inc.
Purpose: This research study will examine the safety and effectiveness of ONS-5010 in participants with AMD. The goal is to prevent vision loss by evaluating the effectiveness of ONS-5010 as compared with ranibizumab.
Design: Randomized, parallel assignment, double masking
Number of Patients: 220
Inclusion Criteria: Active primary or recurrent Subfoveal Choroidal Neovascularization lesions secondary to Age-related macular degeneration (AMD) in the study eye; Best corrected visual acuity of 25-60 letters read (20/60 to 20/320 Snellen equivalent). Study eye must: have active leakage on fluorescein angiogram involving the fovea, have edema involving the fovea, be free of foveal scarring, be free of foveal atrophy.
Exclusion Criteria: Previous use of anti-VEGF or bevacizumab within 6 weeks; Previous subfoveal focal laser photocoagulation in the study eye; Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within 1-month preceding randomization; Any concurrent intraocular condition in the study eye that may require medical or surgical intervention or contribute to vision loss within 1 year; Active intraocular inflammation (grade trace or above) in the study eye; Current vitreous hemorrhage in the study eye; Polypoidal choroidal vasculopathy (PCV) confirmed by indocyanine green angiography (ICGA); History of idiopathic or autoimmune-associated uveitis in either eye; Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye; Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥30 mmHg despite treatment with anti-glaucoma medication); Premenopausal women not using adequate contraception; Current treatment for active systemic infection; Known allergy to any component of the study drug or history of allergy to fluorescein or indocyanine green, not amenable to treatment.
Information: ClinicalStudies@outlooktherapeutics.com
Study: Post Intravitreal Injection Topical NSAID vs Patching
Clinicaltrials.gov Identifier: NCT03918590
Sponsor: The New York Eye & Ear Infirmary
Purpose: A prospective randomized trial, to evaluate postinjection comfort measures comparing topical NSAID (nepafenac 0.3% suspension) and patching.
Design: Randomized, parallel assignment
Number of Patients: 60
Inclusion Criteria: 18 years of age or older; already scheduled for anti-VEGF injection based on standard of care for disease process. Ability to provide written informed consent; Capable of complying with study protocol. Volunteer written informed consent with the understanding that consent may be withdrawn by the subject at any time without prejudice to future care.
Exclusion Criteria: History of past intraocular injection of steroid medication. Experiencing baseline eye pain; monocular; nonstudy eye with VA<20/100. Unwilling or unable to follow or comply with all study related procedures.
Study: Efficacy and Safety Trial of Conbercept Intravitreal Injection for Neovascular Age-related Macular Degeneration (PANDA-1)
Clinicaltrials.gov Identifier: NCT03577899
Sponsor: Chengdu Kanghong Biotech Co., Ltd.
Purpose: The purpose of this clinical study is to evaluate the efficacy and safety of 2 different levels of conbercept intravitreal (IVT) injection as compared to the approved vascular endothelial growth factor (VEGF) antagonist active control, aflibercept intravitreal injection (2.0 mg/eye, Eylea), in subjects with neovascular AMD.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 1,140
Inclusion Criteria: Men and women ≥50 years of age at the screening visit; Females must be at least 1 year postmenopausal, or surgically sterilized, or, if of childbearing potential, must have a negative pregnancy test at the screening visit; Women of childbearing potential must agree to use a highly effective method of contraception throughout the study. Have received no previous treatment for neovascular AMD, including laser photocoagulation and/or photodynamic therapy (PDT) and/or IVT VEGF antagonists (treatment naïve) and; Have active subfoveal choroidal neovascularization (CNV) lesions secondary to AMD (including polypoidal choroidal vasculopathy (PCV)) evidenced by subfoveal fluorescein angiography (FA) leakage, or definite subfoveal fluid by SD-OCT in the study eye at screening; Have a ETDRS BCVA letter score of 78 to 25 in the study eye at screening; Are willing and able to sign the study written informed consent form (ICF).
Exclusion Criteria: Have had any prior ocular or systemic treatment (investigational or approved) or surgery for the treatment of neovascular AMD in the study eye except dietary supplements or vitamins; Have participated as a subject in any interventional clinical trial within 1 month (30 days) prior to baseline visit; Have a subretinal hemorrhage that is either 50% or more of the total lesion area, or blood is under the fovea and is 1 or more disc areas in size (greater than 2.5 mm2) in the study eye at screening; Have any retinal pigment epithelial tears or rips in the study eye at screening or upon examination at baseline; Have any vitreous hemorrhage in the study eye upon examination at baseline or history of vitreous hemorrhage within 8 weeks prior to screening; Have any other cause of CNV; Have had prior pars plana vitrectomy in the study eye; Have presence of a full thickness macular hole at screening or upon examination at baseline or a history of a full thickness macular hole in the study eye; Have prior trabeculectomy or other filtration surgery in the study eye; Have uncontrolled glaucoma; Have active intraocular inflammation in either eye at screening or upon examination at baseline or a history of uveitis in either eye; Have aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of yttrium aluminum garnet (YAG) posterior capsulotomy) in the study eye; Significant media opacities, including cataract, in the study eye that, in the opinion of the Investigator, could require either medical or surgical intervention during the study period; Have any use of long acting intraocular steroids, including implants, within 6 months prior to day 1, baseline; Have any known allergy to povidone iodine or known serious allergy to the fluorescein sodium for injection in angiography; Any history of known contraindications indicated in the Food and Drug Administration (FDA)-approved label for the active control; If female, be pregnant (positive urine pregnancy test at screening) or breastfeeding.
Information: panda@cnkh.com
Study: Efficacy and Safety Trial of Conbercept Intravitreal Injection for Neovascular Age-related Macular Degeneration (PANDA-2)
Clinicaltrials.gov Identifier: NCT03630952
Sponsor: Chengdu Kanghong Biotech Co., Ltd.
Purpose: The purpose of this clinical study is to evaluate the efficacy and safety of 2 different levels of conbercept intravitreal (IVT) injection as compared to the approved vascular endothelial growth factor (VEGF) antagonist active control, aflibercept intravitreal injection (2.0 mg/eye, Eylea), in subjects with neovascular AMD.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 1,140
Inclusion Criteria: Men and women ≥50 years of age at the screening visit; females must be at least 1 year postmenopausal, or surgically sterilized, or, if of childbearing potential, must have a negative pregnancy test at the screening visit; o women of childbearing potential must agree to use a highly effective method of contraception throughout the study. Have received no previous treatment for neovascular AMD, including laser photocoagulation and/or photodynamic therapy (PDT) and/or IVT VEGF antagonists (treatment naïve) and; Have active subfoveal choroidal neovascularization (CNV) lesions secondary to AMD (including polypoidal choroidal vasculopathy (PCV)) evidenced by subfoveal fluorescein angiography (FA) leakage, or definite subfoveal fluid by SD-OCT in the study eye at screening; Have a ETDRS BCVA letter score of 78 to 25 in the study eye at screening; Are willing and able to sign the study written informed consent form (ICF).
Exclusion Criteria: Have had any prior ocular or systemic treatment (investigational or approved) or surgery for the treatment of neovascular AMD in the study eye except dietary supplements or vitamins; Have participated as a subject in any interventional clinical trial within 1 month (30 days) prior to baseline visit; Have a subretinal hemorrhage that is either 50% or more of the total lesion area, or blood is under the fovea and is 1 or more disc areas in size (greater than 2.5 mm2) in the study eye at screening; Have any retinal pigment epithelial tears or rips in the study eye at screening or upon examination at baseline; Have any vitreous hemorrhage in the study eye upon examination at baseline or history of vitreous hemorrhage within 8 weeks prior to screening; Have any other cause of CNV; Have had prior pars plana vitrectomy in the study eye; Have presence of a full thickness macular hole at screening or upon examination at baseline or a history of a full thickness macular hole in the study eye; Have prior trabeculectomy or other filtration surgery in the study eye; Have uncontrolled glaucoma; Have active intraocular inflammation in either eye at screening or upon examination at baseline or a history of uveitis in either eye; Have aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of yttrium aluminum garnet (YAG) posterior capsulotomy) in the study eye. Significant media opacities, including cataract, in the study eye that, in the opinion of the Investigator, could require either medical or surgical intervention during the study period; Have any use of long acting intraocular steroids, including implants, within 6 months prior to day 1, baseline; Have any known allergy to povidone iodine or known serious allergy to the fluorescein sodium for injection in angiography; any history of known contraindications indicated in the Food and Drug Administration (FDA)-approved label for the active control; if female, be pregnant (positive urine pregnancy test at screening) or breastfeeding.
Information: panda@cnkh.com
Study: AAVCAGsCD59 for the Treatment of Wet AMD
Clinicaltrials.gov Identifier: NCT03585556
Sponsor: Hemera Biosciences
Purpose: Patients with treatment naive wet AMD will receive an intravitreal anti-VEGF injection at day 0 followed by an intravitreal injection of AAVCAGsCD59 at day 7. Patients will be followed monthly through Month 12 and receive an intravitreal anti-VEGF injection as needed based on an increase in central subfoveal thickness (CST) of >50 micrometers on OCT from day 0, new subretinal hemorrhage on clinical exam, and/or loss of 10 or more ETDRS letters from the previous month exam.
Design: Single group, no masking
Number of Patients: 25
Inclusion Criteria: Men or women 50 years of age or older. Treatment naive Wet AMD with no evidence of subretinal fibrosis under the fovea. Presence of intraretinal and/or subretinal fluid on OCT. Best corrected visual acuity (BCVA) Snellen equivalent 20/25 to 20/400 in the study eye using ETDRS charts at a starting distance of 4m. Adequate pupillary dilation to permit ocular examination and testing. Ability and willingness to return for all scheduled visits and assessments. Understand and comply with the clinical protocol and provide written informed consent prior to any study-related procedure. All fertile men must be willing to use barrier contraception during the study. Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception for the duration of the trial. A woman of childbearing potential is defined as any female who has had menses within the last 2 years or has not undergone a hysterectomy or surgical sterilization.
Exclusion Criteria: Wet AMD secondary to non-AMD etiologies. Subretinal hemorrhage that interferes with the ability to adequately measure visual acuity or follow retinal or subretinal fluid collection on OCT. Serous pigment epithelial detachment (PED) that is >50% of the CNV lesion, >400µm in any diameter, or presence of an RPE tear. Presence of polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), central serous retinopathy, or symptomatic vitreomacular adhesion. Previous macular laser photocoagulation for CNV, photodynamic therapy (PDT), ocular radiation, or subretinal surgery for CNV in the study eye. History of conditions in the study eye which might alter visual acuity or interfere with study testing including clinically significant macular edema, central retinal vein occlusion, macular branch retinal vein occlusion, and optic neuropathy. Active uncontrolled glaucoma with IOP>30 mmHg despite treatment with glaucoma medications, cup-to-disc ratio of >0.9, visual field defects secondary to glaucoma that involve the macula, and optic atrophy from glaucoma. Likely candidate for intraocular surgery (including cataract surgery) in the study eye during the clinical trial. Acute or chronic infection in the study eye. History of uveitis unrelated to eye surgery in the study eye or opposite eye requiring treatment with topical corticosteroids or systemic immunosuppression within 24 months of enrollment. Any contraindication to intravitreal injection. Use intravitreal (study eye) corticosteroids within 3 months prior to screening. Any of the following underlying systemic diseases: Unstable or severe cardiovascular disease, eg, congestive heart failure (New York Heart Association Functional class III or IV), myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina, or critical limb ischemia; Cerebrovascular disease within 12 months prior to screening that impairs the patient's ability to participate in the clinical trial; Dementia or neurodegenerative disease (eg, Alzheimer's disease, Parkinson's disease) of a level that prevents adequate evaluation of the subject during the study; Has an active malignancy or is currently undergoing treatment for an active malignancy at screening, or has a history of malignancy that precludes completion of this 12-month study; Immunocompromised conditions and/or need for immunosuppressive therapy. Any significant poorly controlled illness that would preclude study compliance and follow-up. Current or prior use of any medication known to be toxic to the retina or optic nerve including, but not limited, to chloroquine/hydrochloroquine, deferoxamine, phenothiazines and ethambutol. Previous treatment with any ocular or systemic gene transfer product. Received any investigational product within 120 days prior to screening. Any psychological, familial, sociological, geographical, or other condition that would preclude study compliance and follow-up.
Information: info@hemerabiosciences.com
Study: A Study to Evaluate the Efficacy and Safety of Faricimab in Participants with Neovascular Age-Related Macular Degeneration (TENAYA)
Clinicaltrials.gov Identifier: NCT03823287
Sponsor: Hoffman-La Roche
Purpose: This study will evaluate the efficacy, safety, durability, and pharmacokinetics of faricimab administered at intervals as specified in the protocol, compared with aflibercept once every 8 weeks (Q8W), in participants with neovascular age-related macular degeneration (nAMD).
Design: Randomized, parallel assignment, triple masking
Number of Patients: 640
Inclusion Criteria: Treatment-naïve choroidal neovascularization (CNV) secondary to age-related macular degeneration (nAMD) in the study eye; ability to comply with the study protocol, in the investigator's judgment; for women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive measures that result in failure rate <1% per year during the treatment period and for at least 3 months after the final dose of study treatment.
Exclusion Criteria: Uncontrolled blood pressure, defined as systolic blood pressure >180 millimeters of mercury (mmHg) and/or diastolic blood pressure >100 mmHg while a patient is at rest on day 1; pregnancy or breastfeeding, or intention to become pregnant during the study; CNV due to causes other than AMD in the study eye; any history of macular pathology unrelated to AMD affecting vision or contributing to the presence of intraretinal or subretinal fluid in the study eye; any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could either reduce the potential for visual improvement or require medical or surgical intervention during the study; uncontrolled glaucoma in the study eye; any prior or concomitant treatment for CNV or vitreomacular-interface abnormalities in the study eye; prior IVT administration of faricimab in either eye; history of idiopathic or autoimmune-associated uveitis in either eye; active ocular inflammation or suspected or active ocular or periocular infection in either eye.
Information: global-roche-genentech-trials@gene.com
Study: A Study to Evaluate the Efficacy and Safety of Faricimab in Participants with Neovascular Age-Related Macular Degeneration (LUCERNE)
Clinicaltrials.gov Identifier: NCT03823300
Sponsor: Hoffman-La Roche
Purpose: This study will evaluate the efficacy, safety, durability, and pharmacokinetics of faricimab administered at intervals as specified in the protocol, compared with aflibercept once every 8 weeks (Q8W), in participants with neovascular age-related macular degeneration (nAMD).
Design: Randomized, parallel assignment, triple masking
Number of Patients: 640
Inclusion Criteria: Treatment-naïve choroidal neovascularization (CNV) secondary to age-related macular degeneration (nAMD) in the study eye; ability to comply with the study protocol, in the investigator's judgment; for women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive measures that result in failure rate <1% per year during the treatment period and for at least 3 months after the final dose of study treatment.
Exclusion Criteria: Uncontrolled blood pressure, defined as systolic blood pressure >180 millimeters of mercury (mmHg) and/or diastolic blood pressure >100 mmHg while a patient is at rest on day 1; pregnancy or breastfeeding, or intention to become pregnant during the study; CNV due to causes other than AMD in the study eye; any history of macular pathology unrelated to AMD affecting vision or contributing to the presence of intraretinal or subretinal fluid in the study eye; any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could either reduce the potential for visual improvement or require medical or surgical intervention during the study; uncontrolled glaucoma in the study eye; any prior or concomitant treatment for CNV or vitreomacular-interface abnormalities in the study eye; prior IVT administration of faricimab in either eye; history of idiopathic or autoimmune-associated uveitis in either eye; active ocular inflammation or suspected or active ocular or periocular infection in either eye.
Information: global-roche-genentech-trials@gene.com
Study: Intense Treatment Regimen With Intravitreal Aflibercept Injection (I-TRAP)
Clinicaltrials.gov Identifier: NCT03594461
Sponsor: Vitreous-Retina-Macula Consultants of New York
Purpose: This study will evaluate the safety and efficacy of intense dosing for a limited period in patients who demonstrate refractory disease on monthly IAI. Patients will be followed for 52 weeks.
Design: Randomized, parallel assignment, no masking
Number of Patients: 30
Inclusion Criteria: Age ≥50 years; choroidal neovascularization related to age-related macular degeneration; prior treatment with any anti-VEGF agent for ≥12 months; prior treatment with at least 5 consecutive IAI at baseline with an average treatment interval of maximum 35 days; presence of foveal fluid at most recent clinical visit occurring 30 (+/-5) days following the most recent IAI; willing and able to comply with clinic visits and study-related procedures; provide signed informed consent.
Exclusion Criteria: Monocular patients; patients with a previous history of macular thermal laser or PDT; confounding ocular conditions in the study eye that may affect interpretation of OCT, BCVA or assessment of macular appearance (eg, cataract, epiretinal membrane, retinal vascular occlusive disease); intraocular surgery (including cataract surgery) in the study eye within 2 months preceding baseline; history of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in the study eye; active intraocular inflammation (grade trace or above) in the study eye; history of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye; uncontrolled glaucoma in the study eye (defined as IOP ≥30 mmHg despite treatment with anti-glaucoma medication); history of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 3 months of study enrollment; patients on systemic anti-VEGF treatment; pregnant or breastfeeding women; sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception prior to the initial dose/start of the first treatment, during the study, and for at least 3 months after the last dose. Adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly. *Contraception is not required for men with documented vasectomy. **Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
Information: sariahpersaud@vrmny.com, rsalgado@vrmny.com
Study: Exploratory Study to Investigate the Bioactivity, Ocular and Systemic Safety, Tolerability, and Pharmacokinetics Following Single and Multiple Intravitreal Administrations of KSI-301 in Subjects With wAMD, DME and RVO
Clinicaltrials.gov Identifier: NCT03790852
Sponsor: Kodiak Sciences, Inc.
Purpose: This is a phase 1b open-label study to assess the bioactivity, ocular and systemic safety, tolerability, and pharmacokinetics of repeated injections of KSI-301 at 2 dose levels: 2.5 mg and 5 mg.
Design: Randomized, parallel assignment, no masking
Number of Patients: 50
Inclusion Criteria: Wet AMD Cohort: Treatment naïve wet age-related macular degeneration involving the fovea. A lesion area <30 mm2 (12 disc areas) of any lesion type. BCVA ETDRS letter score ≤78 and ≥23 (⁓20/25 to ⁓20/320 Snellen equivalent) in the study eye. Decrease in vision in the study eye determined by the investigator to be primarily the result of wet AMD.
Exclusion Criteria: Wet AMD Cohort: Choroidal neovascularization due to causes other than age-related macular degeneration in the study eye. Geographic atrophy and/or subretinal fibrosis involving the fovea of the study eye. Prior intravitreal anti-VEGF therapy in the study eye.
Information: jehrlich@kodiak.com, pablovm@kodiak.com
Study: Study of Safety and Efficacy of Brolucizumab 6 mg Dosed Every 4 Weeks Compared to Aflibercept 2 mg Dosed Every 4 Weeks in Patients with Retinal Fluid Despite Frequent Anti-VEGF Injections (MERLIN)
Clinicaltrials.gov Identifier: NCT03710564
Sponsor: Novartis Pharmaceuticals
Purpose: The purpose of this study is to compare safety and efficacy of brolucizumab 6 mg dosed every 4 weeks to aflibercept 2 mg dosed every 4 weeks in those nAMD patients with retinal fluid despite frequent anti-Vascular Endothelial Growth Factor (VEGF) injections.
Design: Multicenter, randomized, double-masked
Number of Patients: 500
Inclusion Criteria: Sign informed consent; diagnosis of wet age-related macular degeneration (AMD); currently receiving anti-VEGF injections.
Exclusion Criteria: Active infection or inflammation in either eye; significant fibrosis in the study eye; recent ocular surgery; uncontrolled glaucoma; previous treatment with brolucizumab in the study eye; use of medications as specified in the protocol; pregnant, nursing; of child-bearing potential unless using highly effective method of contraception; other protocol-defined inclusion/exclusion criteria may apply.
Information: novartis.email@novartis.com
Study: ADVM-022 Gene Therapy for Wet AMD (OPTIC)
Clinicaltrials.gov Identifier: NCT03748784
Sponsor: Adverum Biotechnologies, Inc.
Purpose: ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product developed for the treatment of neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is a serious condition and the leading cause of blindness in the elderly. The available therapies for treating wet AMD require lifelong intravitreal (IVT) injections every 4-12 weeks to maintain efficacy. A one-time administration of ADVM-022 has the potential to treat wet AMD by providing durable expression of therapeutic levels of intraocular anti-VEGF protein (aflibercept) and preserving the vision of patients. ADVM-022 is designed to reduce the current treatment burden and the adverse events (AEs) associated with chronic IVT injections.
Design: Nonrandomized, sequential assignment, open label
Number of Patients: 18
Inclusion Criteria: Age ≥50; diagnosis of neovascular (wet) AMD; BCVA ETDRS Snellen equivalent between ≤20/80 and ≥20/320 for the first (sentinel) patient in each cohort followed by BCVA ETDRS Snellen equivalent between ≤20/40 and ≥20/320 for the rest of the cohort; subjects must be under active anti-VEGF treatment for wAMD and received a minimum of 2 injections within 4 months prior to screening; up to a maximum of 6 injections within 8 months prior to screening; demonstrated a meaningful response to anti-VEGF therapy; willing and able to provide consent.
Exclusion Criteria: History of retinal disease in the study eye other than wet AMD; fibrosis or atrophy, retinal epithelial tear in the center of the fovea in the study eye, or any condition preventing visual acuity improvement; history of retinal detachment (with or without repair) in the study eye; history of vitrectomy, trabeculectomy, or other filtration surgery in the study eye; uncontrolled glaucoma in the study eye; any prior treatment with photodynamic therapy or retinal laser for the treatment of wet AMD and any previous therapeutic radiation in the region of the study eye; any previous intraocular or periocular surgery on the study eye within 6 months; acute coronary syndrome, myocardial infarction or coronary artery revascularization, CVA, TIA in the last 6 months; uncontrolled hypertension defined as average SBP ≥160 mmHg or an average DBP ≥100 mmHg.
Information: stong@adverum.com
Study: A Phase III Study to Evaluate the Port Delivery System Implant with Ranibizumab Compared with Monthly Ranibizumab Injections in Participants with Wet Age-Related Macular Degeneration (Archway)
Clinicaltrials.gov Identifier: NCT03677934
Sponsor: Hoffman-La Roche
Purpose: Study GR40548 is a phase III, randomized, multicenter, open-label (visual assessor [VA]-masked), active-comparator study designed to assess the efficacy, safety, and pharmacokinetics (PK) of 100mg/ml delivered via the Port Delivery System (PDS) compared with ranibizumab intravitreal injections at 0.5 mg (10 mg/mL) in participants with neovascular age-related macular degeneration (nAMD).
Design: Randomized, parallel assignment, single masking
Number of Patients: 360
Inclusion Criteria: Age ≥50 years, at time of signing Informed Consent Form. Initial diagnosis of exudative neovascular age-related macular degeneration (nAMD) within 9 months prior to the screening visit. Previous treatment with at least 3 anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections for nAMD per standard of care within 6 months prior to the screening visit. Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis. Best-corrected visual acuity (BCVA) of 34 letters or better.
Exclusion Criteria: Subfoveal fibrosis or subfoveal atrophy in study eye. Subretinal hemorrhage that involves the center of the fovea in study eye. History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in study eye. Prior treatment with Visudyne, external-beam radiation therapy, or transpupillary thermotherapy in study eye. Previous intraocular device implantation in study eye. Previous laser (any type) used for AMD treatment in study eye. Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit in either eye. Prior participation in a clinical trial involving anti-VEGF drugs within 6 months prior to the randomization visit, other than ranibizumab in either eye. CNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia in either eye. Uncontrolled blood pressure. History of stroke within the last 3 months prior to informed consent. Uncontrolled atrial fibrillation within 3 months of informed consent. History of myocardial infarction within the last 3 months prior to informed consent. History of other disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the Implant and that might affect interpretation of the results of the study or renders the participant at high risk of treatment complications in the opinion of the investigator. Current systemic treatment for a confirmed active systemic infection. Chronic use of oral corticosteroids. Active cancer within 12 months of randomization. Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals).
Information: global-roche-genentech-trials@gene.com
Study: NEAMES: Episcleral Brachytherapy for the Treatment of Wet AMD
Clinicaltrials.gov Identifier: NCT02988895
Sponsor: Salutaris Medical Devices, Inc.
Purpose: This is a prospective, single-arm, open-label, safety, usability and tolerability trial of Strontium 90 (Sr90) beta radiation episcleral brachytherapy in subjects receiving aflibercept therapy pro re nata (PRN) for the treatment of early neovascular age-related macular degeneration (nAMD) lesions. Secondary aims are to observe clinical outcomes of area of leakage, subretinal fluid, lesion size, visual acuity, and anti-vascular endothelial growth factor (anti-VEGF) treatment burden.
Design: Single Group, No Masking, Treatment
Number of Patients: 20
Inclusion Criteria: Diagnosis of CNV due to nAMD; Male or female aged 50 years or older; Documented continued care for nAMD since diagnosis; Patients must have demonstrated clinical or OCT/angiographic evidence that, in the investigator's opinion, requires treatment with anti-VEGF therapy; BCVA 20/40 - 20/200 Snellen equivalent in study eye; Actively leaking CNV as determined by FA.
Exclusion Criteria: Females of child-bearing potential (defined as <2 years postmenopausal) CNV other than due to nAMD; Subfoveal lesion hemorrhage obscuring >50% of lesion; CNV lesion with greatest linear dimension >2mm as determined by Intravenous Fluorescein angiography; Presence of subretinal fibrosis in the study eye; Existing Retinal Pigment Epithelial tear; Previous treatment (excluding vitamins) for nAMD in the study eye other than aflibercept anti-VEGF therapy in the last 6 months; A change in anti-VEGF agent in the previous 2 administrations; Anticipate a change to the anti-VEGF agent during the conduct of the study; Previous intraocular surgery in study eye other than for uncomplicated phacoemulsification cataract extraction; Other clinically significant ocular co-morbidity including, but not limited to, optic glaucoma, optic neuropathy of any cause, maculopathy/retinopathy of any cause other than nAMD, and scleritis; Refractive error of -6D or greater (spherical equivalent) or demonstrated myopic degeneration; Media opacity sufficient to preclude adequate fundoscopy, OCT or angiography; Uncontrolled systemic diseases (eg, controlled hypertension is acceptable); Type I or type II diabetes mellitus; Clinically significant previous radiation to the eye; Unable to discontinue anticoagulation or dual anti-platelet therapy for 7 days before and after the study intervention.; Patient unsuitable for IV or local anesthesia; Any contraindication to anti-VEGF, fluorescein, topical and local anesthetics, topical antiseptics, or topical antibiotics to be used during the study; Active ocular or periocular infection or intraocular inflammation; Only eligible eye is the best seeing eye; Any condition which, in the investigators' opinion, would conflict or otherwise prevent the subject from complying with the required procedures, schedule or other study conduct.
Information: mdrew@salutarismd.com
Study: IAI-OCTA: A study of OCT-Angiography Analysis Efficacy
Clinicaltrials.gov Identifier: NCT03022292
Sponsor: University of California, Los Angeles
Purpose: This study is utilizing a new, FDA approved, nonstandard of care technology (OCT-Angiography by Optovue) to image and evaluate the treatment outcomes of using standard of care Intravitreal Aflibercept Injections for their approved use in patients diagnosed with neovascular AMD who are naive to previous Anti-VEGF therapies.
Design: Single Group Assignment, No Masking
Number of Patients: 30
Inclusion Criteria: Older than 50; willing to participate in the study and able to follow study criteria and protocol; the study eye is treatment naïve regarding treatment of neovascular AMD; subject is willing and able to comply with clinic visits and study-related procedures; subject is able to provide signed informed consent; subject is able to understand and complete study-related questionnaires; subject is not currently involved with any other clinical study; BCVA with ETDRS Snellen equivalent of 20/400 or better and 20/32 or worse; sufficiently clear media (cornea, anterior chamber, lens, vitreous) for OCT, FA and fundus photography; IOP of 25 mmHg or less in the study eye, with or without use of ocular hypotensive agents; prior focal corticosteroid treatment is allowed, as long as the study eye is not involved. However prior (within 90 days of day 0) or current systemic corticosteroid therapy (oral or intravenous corticosteroid treatment) is not permitted.
Exclusion Criteria: Any prior treatment of neovascular AMD in the eye proposed for enrollment including previous anti-vascular endothelial factor (anti-VEGF) therapy, photodynamic therapy (PDT), radiation therapy, corticosteroid treatment, surgical treatment for CNV, thermal laser treatment, and any other prior intravitreal treatment for neovascular AMD (except minerals and vitamins); known serious allergies to aflibercept, fluorescein dye, Indocyanine Green (ICG), shellfish, drugs for pupillary dilation, topical anesthetic, or sterilizing solution (eg, Betadine Solution); prior or current systemic anti-VEGF therapy; pregnant or breast-feeding women; sexually active men or women of childbearing potential who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly); contraindication to pupillary dilation in study eye; any condition (including inability to read visual acuity charts, or language barrier) that may preclude subjects ability to comply with the study protocol and requirements; presence of any advanced systemic condition or end-stage disease, such as advanced Alzheimer Syndrome, end-stage cancer, etc., which will likely prevent subject from completing study; previous therapeutic radiation in the region of the study eye; prior retinal pigment epithelial (RPE) tear in study eye; prior ocular surgery (except YAG laser capsulotomy) for study within the past 90 days; anticipated ocular surgery 9except YAG laser capsulotomy) for the next 12 months; prior vitrectomy in the study eye; presence of any causes of CNV and PED other than due to AMD or presence of ocular disease other than AMD affecting study eye, ie presumed ocular histoplasmosis syndrome, android streaks, pathologic myopia.
Information: harmon@jsei.ucla.edu, downey@jsei.ucla.edu
Study: RGX-314 Gene Therapy for Neovascular AMD Trial
Clinicaltrials.gov Identifier: NCT03066258
Sponsor: Regenxbio Inc.
Purpose: To test RGX-314’s ability to treat neovascular AMD.
Design: Nonrandomized, sequential assignment, no masking, treatment
Number of Patients: 18
Inclusion Criteria: Patients ≥50 years with a diagnosis of subfoveal CNV secondary to AMD in the study eye receiving prior intravitreal anti-VEGF therapy; BCVA between ≤20/100 and ≥20/400 (≤53 and ≥19 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) for the first patient in each cohort followed by BCVA between ≤20/63 and ≥20/400 (≤75 and ≥35 ETDRS letters) for the rest of the cohort; history of need for and response to anti-VEGF therapy; response to anti-VEGF at trial entry (assessed by SD-OCT at week 1); must be pseudophakic (status post cataract surgery) in the study eye; AST/ALT <2.5×ULN; TB <1.5×ULN; PT <1.5×ULN; Hb >10 g/dL (males) and >9 g/dL (females); Platelets >100×10^3/µL; eGFR >30 mL/min/1.73 m^2; must be willing and able to provide written, signed informed consent.
Exclusion Criteria: CNV or macular edema in the study eye secondary to any causes other than AMD; any condition preventing visual acuity improvement in the study eye, eg, fibrosis, atrophy, or retinal epithelial tear in the center of the fovea; active or history of retinal detachment in the study eye; advanced glaucoma in the study eye; history of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to screening; presence of an implant in the study eye at screening (excluding intraocular lens); myocardial infarction, cerebrovascular accident, or transient ischemic attacks within the past 6 months; uncontrolled hypertension (systolic blood pressure [BP] >180 mmHg, diastolic BP >100 mmHg) despite maximal medical treatment.
Information: patientadvocacy@regenxbio.com
DIABETIC MACULAR EDEMA
NEW: Study: A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of IVT MHU650 in Macular Edema Patients
Clinicaltrials.gov Identifier: NCT04635800
Sponsor: Novartis Pharmaceuticals
Purpose: This open-label study is being conducted to evaluate the initial safety and tolerability of IVT MHU650 in patients with DME, AMD, or RVO. The primary objective of this study is to evaluate the safety and tolerability of single ascending doses of IVT MHU650 in patients with macular edema. The secondary objective of this study is to evaluate the serum pharmacokinetic profile of total MHU650 following single IVT dose of MHU650 in macular edema patients.
Design: Nonrandomized, sequential assignment, no masking
Number of Patients: 18
Inclusion Criteria: Patients with macular edema in at least one eye, including those with focal or diffuse diabetic macular edema (DME), neovascular age-related macular degeneration (AMD), or retinal vein occlusion (RVO), in the opinion of the investigator: Early Treatment Diabetic Retinopathy (ETDRS) letter score in the study eye must be worse than 60 letters (20/63) but better than 24 letters (20/320) at screening and baseline. The ETDRS score in the non-study eye should be ≥ 60 letters at screening and baseline. Sufficiently clear ocular media and adequate pupil dilation to permit fundus photographs of adequate clarity to measure diameters of retinal arteries and veins. Vital signs as specified in the protocol.
Exclusion Criteria: Proliferative diabetic retinopathy in the study eye. The following is permitted as an exception: Tufts of neovascularization less than one disc area with no vitreous hemorrhage. Focal, peripheral retinal areas treated with photocoagulation with fewer than 30 laser burns performed at least 6 months preceding Day 1. Patients with type 1 or type 2 diabetes who have hemoglobin A1C of ≥ 12 at screening. Other ocular conditions as specified in the protocol. Systemic conditions as specified in the protocol. Other protocol-defined inclusion/exclusion criteria may apply.
Information: novartis.email@novartis.com
NEW: Study: Safety and Bioactivity of AXT107 in Subjects With Diabetic Macular Edema (CONGO)
Clinicaltrials.gov Identifier: NCT04697758
Sponsor: Asclepix Therapeutics, Inc.
Purpose: This study is an open-label, dose-escalating, 48-week study assessing the safety, tolerability, bioactivity and duration of action of a single intravitreal injection of 0.1 mg, 0.25 mg, or 0.5 mg AXT107 in approximately 18 subjects (up to 6 subjects per dose) with Diabetic Macular Edema (DME).
Design: Nonrandomized, sequential assignment, no masking
Number of Patients: 18
Inclusion Criteria: Patients 18 years of age or older with diabetic macular edema (DME) diagnosis secondary to diabetes mellitus Type 1 or 2. Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 65 to 23 in the study eye. Willing and able to comply with clinic visits and study-related procedures. Provide signed inform consent.
Exclusion Criteria: Any signs of high risk proliferative diabetic retinopathy in the study. Previously-treated patients who are not responders to anti-VEGF. Panretinal laser photocoagulation within 6 months and macular laser photocoagulation with 3 months of screening in the study eye. Note: Other inclusion/exclusion criteria apply.
Information: info@asclepix.com
NEW: Study: A Study to Evaluate the Long-Term Safety and Tolerability of Faricimab in Participants With Diabetic Macular Edema (Rhone-X)
Clinicaltrials.gov Identifier: NCT04432831
Sponsor: Hoffmann-La Roche
Purpose: This is a multicenter long-term extension study designed to evaluate the long-term safety and tolerability of faricimab administered by intravitreal (IVT) injection at a personalized treatment interval (PTI) to participants who enrolled in and completed one of the two Phase III studies, GR40349 (NCT03622580) or GR40398 (NCT03622593), also referred to as the parent studies.
Design: Single group, no masking
Number of Patients: 1,800
Inclusion Criteria: Previous enrollment in and completion of Study GR40349 (NCT03622580) or GR40398 (NCT03622593), without study or study drug discontinuation. Ability to comply with the study protocol, in the investigator's judgment. For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 3 months after the final dose of study treatment.
Exclusion Criteria: Pregnant or breastfeeding, or intending to become pregnant during the study or within 28 days after the final intravitreal injection of faricimab. Presence of other ocular diseases that give reasonable suspicion of a disease or condition that contraindicates the use of faricimab, that might affect interpretation of the results of the study or that renders the patient at high risk for treatment complications. Presence of other diseases, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of faricimab and that might affect interpretation of the results of the study or that renders the patient at high risk of treatment complications. History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the faricimab injections, study treatment procedure, dilating drops, or any of the anesthetic and antimicrobial preparations used by a patient during the study. Requirement for continuous use of any medications or treatments indicated as prohibited therapy.
NEW: Study: A Study to Investigate Aqueous Humor and Multimodal Imaging Biomarkers in Treatment-Naïve Participants With Diabetic Macular Edema Treated With Faricimab (ALTIMETER)
Clinicaltrials.gov Identifier: NCT04597918
Sponsor: Hoffmann-La Roche
Purpose: This is an exploratory, prospective, multicenter, open-label, single-arm, interventional, Phase IIb study designed to explore the associations over time between clinical assessments, multimodal imaging assessments, aqueous humor (AH) biomarker patterns, and genetic polymorphisms in participants with diabetic macular edema (DME) who are treated with faricimab.
Design: Single group, no masking
Number of Patients: 80
Inclusion Criteria: Diagnosis of diabetes mellitus (Type 1 or Type 2), as defined by the World Health Organization (WHO) and/or American Diabetes Association. Hemoglobin A1c (HbA1c) ≤10%. Patients who are intravitreal (IVT) treatment-naïve in the study eye. Diabetic macular edema (DME) defined as macular thickening by spectral-domain optical coherence tomography (SD-OCT) involving the center of the macula. This inclusion criterion is to be assessed by the central reading center (CRC). Moderately severe to severe non-proliferative DR (NPDR). This inclusion criterion is to be assessed by the CRC. Decreased visual acuity (VA) attributable primarily to DME. Clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images to confirm diagnosis.
Exclusion Criteria: Currently untreated diabetes mellitus or previously untreated patients who initiated oral or injectable anti-diabetic medication within 3 months prior to Day 1. Any known hypersensitivity to any of the components in the faricimab injection, dilating eye drops, or any of the anesthetics and antimicrobial preparations used by the patient during the study. Any major illness or major surgical procedure within 1 month before the Day 1. One re-screening for this criterion is permitted. History of other diseases, other non-diabetic metabolic dysfunction, physical examination finding, historical or current clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of the faricimab or that might affect interpretation of the results of the study or renders the patient at high-risk for treatment complications, in the opinion of the Investigator. Active cancer within the past 12 months prior to Day 1 except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of ≤6 and a stable prostate-specific antigen for >12 months. Stroke or myocardial infarction within 12 months prior to the Day 1. One re-screening for this criterion is permitted. Any febrile illness within 1 week prior to Day 1. One re-screening for this criterion is permitted. Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of faricimab. Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within 6 months prior to Day 1 or anticipated to require hemodialysis or peritoneal dialysis at any time during the study. Any condition resulting in a compromised immune system that is likely to impact the aqueous humor (AH) inflammatory biomarkers. Patients who are currently enrolled in or have participated in any other clinical study involving an investigational product or device, or in any other type of medical research, within 3 months or 5 half-lives prior to Day 1 and up to completion of the current study. Substance abuse occurring within 12 months prior to screening, in the Investigator's judgment. Use of systemic immunomodulatory treatments within 6 months or 5 half-lives prior to Day 1, systemic corticosteroids within 1 month prior to Day 1. Any prior or concomitant systemic anti-VEGF treatment within 6 months or 5 half-lives prior to Day 1. Use of systemic medications known to be toxic to the lens, retina or optic nerve used during the 6-month period or 5 half-lives prior to Day 1 or likely need to be used. Received a blood transfusion within 3 months prior to the screening visit, received any treatment that leads to immunosuppression within 6 months or 5 half-lives prior to Day 1. Ocular Exclusion Criteria for Study Eye: Mild or moderate NPDR. This exclusion criterion is to be assessed by the CRC. Any history of or ongoing rubeosis iridis. Any panretinal photocoagulation or macular laser photocoagulation treatment received in the study eye prior to the screening visit or expected to be received between the screening visit and Day 1. Any history of treatment with anti-VEGF or any periocular or IVT corticosteroids in the study eye and no such treatment planned for the time between screening and Day 1. Any treatment for dry eye disease in the last month prior to Day 1. Lubricating eye drops and ointments are permitted. Any treatment with anti-inflammatory eye drops within 1 month prior to Day 1. Any intraocular surgery within 3 months prior to Day 1 or any planned surgery during the study, any glaucoma surgery prior to the screening visit. History of vitreoretinal surgery/pars plana vitrectomy, corneal transplant, or radiotherapy. Any active or suspected ocular or periocular infections on Day 1. Any presence of active intraocular inflammation on Day 1 or any history of intraocular inflammation. Any history of idiopathic, infectious, or noninfectious uveitis. Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision. Any current ocular condition or other causes of visual impairment for which, in the opinion of the Investigator, VA loss would not improve from resolution of macular edema. Ocular Exclusion Criteria for Fellow Eye: Patient is currently receiving treatment with brolucizumab or bevacizumab in the non-study eye and is unwilling to switch to a protocol allowed non-study eye treatment during the study. Any previous treatment with Iluvien or Retisert in the non-study eye. Non-functioning non-study eye.
Information: global-roche-genentech-trials@gene.com
Study: A Study of Intravitreal ILUVIEN Implant as Baseline Therapy in Patients With Early Diabetic Macular Edema (DME) (NEW DAY)
Clinicaltrials.gov Identifier: NCT04469595
Sponsor: Alimera Sciences
Purpose: This is a randomized, masked, active-controlled, parallel-group, multi-center study that will assess the efficacy of ILUVIEN as a baseline therapy in the treatment of Center Involving DME (CI-DME). The study will enroll patients who are either treatment naïve or have not received any DME treatments for the preceding 12 months as documented in medical records. Patients who received DME treatment >12 months before screening, must not have received >4 intravitreal injections. The study will compare 2 treatment regimens: ILUVIEN intravitreal implant (0.19 mg) followed by supplemental aflibercept as needed per protocol criteria (2 mg/0.05 mL), compared to intravitreal aflibercept loading dose (2 mg administered by intravitreal injection every 4 weeks for 5 consecutive doses) followed by supplemental aflibercept as needed per protocol criteria (2 mg/0.05 mL).
Design: randomized, parallel assignment, double masking
Number of Patients: 300
Inclusion Criteria: Male or female subjects ≥18 years of age at the time of consent. Must have CI-DME confirmed by spectral domain ocular coherence tomography (SD-OCT) and center subfield thickness (CST) of: ≥350 µm in the study eye. Best corrected visual acuity (BCVA) of ≤80 ETDRS letters and ≥35 ETDRS letters in the study eye at screening visit.
Exclusion Criteria: Patients with proliferative diabetic retinopathy (PDR); high risk proliferative diabetic retinopathy in the study eye and related complications. History or current diagnosis of glaucoma or ocular hypertension (OHT) or a cup to disc ratio >0.8; History of uncontrolled intraocular pressure (defined as IOP ≥25 mmHg with maximum topical and systemic medical hypotensive treatment) or previous filtration surgery in the study eye at screening visit. Other conditions that can cause macular edema. Patients who received prior LASER photocoagulation therapy including macular grid or pan retina photocoagulation (PRP) at any time in the study eye. Prior focal LASER photocoagulation therapy outside the macula is allowed. Patients who received the following therapies in the last 12 months prior to screening: Intravitreal or periocular steroids in the study eye; Any intravitreal anti-VEGF [vascular endothelial growth factor (VEGF)] (including but not limited to bevacizumab, ranibizumab, or aflibercept); Patients who received intravitreal anti-VEGF or corticosteroids >12 months prior to the Screening Visit will be allowed in the study, provided that they have not received a total of >4 injections. Patients who have lens opacities due to cataract or other etiologies that would make it difficult to examine the fundus or that affect the patients Activities of Daily Living (ADL). Steroid Challenge Exclusion Criterion- At the Baseline Visit, patients who are determined to have an IOP ≥25 mmHg or an increase ≥8 mmHg from Screening will be excluded from the study.
Information: rachel.nelson@alimerasciences.com
Study: A Trial to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME) (GLEAM)
Clinicaltrials.gov Identifier: NCT04611152
Sponsor: Kodiak Sciences Inc
Purpose: This phase 3 study will evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept in participants with treatment-naïve DME.
Design: randomized, parallel assignment, triple masking
Number of Patients: 450
Inclusion Criteria: Signed informed consent prior to participation in the study. Treatment-naïve diabetic macular edema, with vision loss and center involvement (if present) diagnosed within 9 months of screening. BCVA ETDRS letter score between 78 and 25 (-20/25 to 20/320 Snellen equivalent), inclusive, in the Study Eye. CST of ≥ 320 microns on SD-OCT (Heidelberg Spectralis or equivalent on other OCT instruments) as determined by the Reading Center. Decrease in vision determined by the Investigator to be primarily the result of DME. Type 1 or Type 2 diabetes mellitus and a HbA1c of ≤12%. Other protocol-specified inclusion criteria may apply.
Exclusion Criteria: Macular edema in the Study Eye considered to be secondary to a cause other than DME. Active iris or angle neovascularization or neovascular glaucoma in the Study Eye. High-risk proliferative diabetic retinopathy characteristics in the Study Eye. History of Pan-retinal Photocoagulation (PRP) laser in the Study Eye within 3 months of screening. Tractional retinal detachment in the Study Eye. Active retinal disease other than the condition under investigation in the Study Eye. Any history or evidence of a concurrent ocular condition present, that in the opinion of the Investigator could require either medical or surgical intervention or affect macular edema or alter visual acuity during the study (e.g., vitreomacular traction, epiretinal membrane). Active or suspected ocular or periocular infection or inflammation in either eye at day 1. Any prior use of an approved or investigational treatment for DME in the Study Eye (e.g., anti-VEGF, intraocular or periocular steroids, macular laser photocoagulation). Women who are pregnant or lactating or intending to become pregnant during the study. Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥100 mmHg while at rest. Recent history (within the 6 months prior to screening) of myocardial infarction, stroke, transient ischemic attack, acute congestive heart failure or any acute coronary event. History of a medical condition that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product. Other protocol-specified exclusion criteria may apply.
Information: ksi301clinical@kodiak.com
Study: A Study to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME) (GLIMMER)
Clinicaltrials.gov Identifier: NCT04603937
Sponsor: Kodiak Sciences Inc
Purpose: This phase 3 study will evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept in participants with treatment-naïve DME.
Design: randomized, parallel assignment, triple masking
Number of Patients: 450
Inclusion Criteria: Signed informed consent prior to participation in the study. Treatment-naïve diabetic macular edema, with vision loss and center involvement (if present) diagnosed within 9 months of screening. BCVA ETDRS letter score between 78 and 25 (-20/25 to 20/320 Snellen equivalent), inclusive, in the Study Eye. CST of ≥ 320 microns on SD-OCT (Heidelberg Spectralis or equivalent on other OCT instruments) as determined by the Reading Center. Decrease in vision determined by the Investigator to be primarily the result of DME. Type 1 or Type 2 diabetes mellitus and a HbA1c of ≤12%. Other protocol-specified inclusion criteria may apply.
Exclusion Criteria: Macular edema in the Study Eye considered to be secondary to a cause other than DME. Active iris or angle neovascularization or neovascular glaucoma in the Study Eye. High-risk proliferative diabetic retinopathy characteristics in the Study Eye. History of Pan-retinal Photocoagulation (PRP) laser in the Study Eye within 3 months of screening. Tractional retinal detachment in the Study Eye. Active retinal disease other than the condition under investigation in the Study Eye. Any history or evidence of a concurrent ocular condition present, that in the opinion of the Investigator could require either medical or surgical intervention or affect macular edema or alter visual acuity during the study (e.g., vitreomacular traction, epiretinal membrane). Active or suspected ocular or periocular infection or inflammation in either eye at day 1. Any prior use of an approved or investigational treatment for DME in the Study Eye (e.g., anti-VEGF, intraocular or periocular steroids, macular laser photocoagulation). Women who are pregnant or lactating or intending to become pregnant during the study. Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥100 mmHg while at rest. Recent history (within the 6 months prior to screening) of myocardial infarction, stroke, transient ischemic attack, acute congestive heart failure or any acute coronary event. History of a medical condition that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product. Other protocol-specified exclusion criteria may apply.
Information: ksi301clinical@kodiak.com
Study: RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Diabetic Retinopathy (DR) Without Center Involved-Diabetic Macular Edema (CI-DME) (ALTITUDE)
Clinicaltrials.gov Identifier: NCT04567550
Sponsor: Regenxbio Inc.
Purpose: RGX-314 is being developed as a novel one-time gene therapy treatment for the treatment of diabetic retinopathy, a chronic and progressive complication of diabetes mellitus. Diabetic retinopathy is a sight-threatening disease characterized in the early stages by neuronal and vascular dysfunction in the retina, and later by neovascularization that leads to further deterioration of functional vision. Despite the availability of current treatments, diabetic retinopathy remains the leading cause of vision loss in working-age adults, those between the ages of 20 and 74. Existing treatment with anti-VEGF agents, although shown to be effective, are limited by short therapeutic half-lives, which then require frequent intravitreal injections over the patient's lifetime, resulting in increased risk of associated adverse events and significant treatment burden. Due to the burden of treatment, patients often do not closely adhere to treatment regimens and experience sub-optimal outcomes and a decline in vision. RGX-314 is being developed as a potential one time treatment for diabetic retinopathy, which may deliver advantages over conventional treatments, such as potentially providing a longer duration of therapeutic effect and intervening at an earlier stage of the disease.
Design: Randomized, parallel assignment, no masking
Number of Patients: 40
Inclusion Criteria: Patients 25-89 years of age with a diabetic retinopathy diagnosis of nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) secondary to diabetes mellitus type 1 or 2 for which PRP or anti-VEGF injections can be safely deferred for at least 6 months. Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better). Prior history of CI-DME in the study eye is acceptable. Must be willing and able to provide written, signed informed consent.
Exclusion Criteria: Neovascularization in the study eye from a cause other than DR. Presence of any active CI-DME. Active or history of retinal detachment in the study eye. Any evidence or documented history of PRP or retinal laser in the study eye. Patients who had a prior vitrectomy surgery. Women of childbearing potential.
Information: patientadvocacy@regenxbio.com
Study: A 3-month Study to Assess the Safety of ONS-5010 in Subjects With Visual Impairment Due to Retinal Disorders
Clinicaltrials.gov Identifier: NCT04516278
Sponsor: Outlook Therapeutics, Inc.
Purpose: The study will evaluate the safety of ophthalmic bevacizumab in subjects diagnosed with a retinal condition that would benefit from treatment with intravitreal injection of bevacizumab, including exudative age-related macular degeneration, diabetic macular edema, or branch retinal vein occlusion.
Design: Single group, no masking
Number of Patients: 180
Inclusion Criteria: Active clinical diagnosis and OCT confirmation of one of the following retinal disorders: exudative age-related macular degeneration (AMD), diabetic macular edema (DME), or branch retinal vein occlusion (BRVO) and, in the opinion of the Investigator, requires treatment with an anti-VEGF therapy.
Exclusion Criteria: Previous use of approved anti-VEGF or Avastin® within 4 weeks preceding randomization. Macular edema due to something other than exudative AMD, DME or BRVO, in the study eye. History of inadequate response to previous intravitreal anti-VEGF therapy. History of any intraocular or periocular corticosteroid injection or implant, in the study eye. Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within 1-month preceding randomization. Any concurrent intraocular condition in the study eye that may require medical or surgical intervention or contribute to vision loss during the study period. Active intraocular inflammation in the study eye. Current vitreous hemorrhage in the study eye. Polypoidal choroidal vasculopathy (PCV) in the study eye. History of idiopathic, infectious or autoimmune-associated uveitis in either eye. Current ocular or periocular infection, such as conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye. Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥30 mmHg despite treatment with anti-glaucoma medication). Premenopausal women not using adequate contraception. Current treatment for active systemic infection. Known allergy to any component of the study drug, not amenable to treatment.
Information: jenniferkissner@outlooktherapeutics.com
Study: Safety and Tolerability Study of UBX1325 in Patients With Diabetic Macular Edema
Clinicaltrials.gov Identifier: NCT04537884
Sponsor: Unity Biotechnology, Inc.
Purpose: A study to evaluate safety, tolerability, and pharmacokinetics of a single intravitreal injection of UBX1325 in patients diagnosed with diabetic macular edema (DME).
Design: Single group, no masking
Number of Patients: 21
Inclusion Criteria: Nonproliferative diabetic retinopathy (DR) patients with DME. Center-involved DME with central subfield thickness (CST) ≥350 μm on SD-OCT. BCVA in the study eye (most affected) of 35 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or worse of 6 months duration or longer prior to screening. Patients who have the capacity to give informed consent and who are willing and able to comply with all study-related procedures and assessments.
Exclusion Criteria: Any ocular/intraocular/periocular infection or inflammation in either eye. History of vitreous hemorrhage in the study eye within 2 months prior to screening. Any retinovascular disease or retinal degeneration other than DME in the study eye. History of systemic and intraocular steroid use for 6 months prior to day 1. The use of intravitreal nonbiodegradable steroid implants (ex. Iluvien, Yutiq, Retisert) is prohibited. Significant media opacities, including cataract, which might interfere with VA, assessment of toxicity, or fundus imaging. Any uncontrolled medical condition that, in the opinion of the investigator, would preclude participation in this study.
Information: UBX1325-01_medicalmonitor@unitybiotechnology.com
Study: A Study to Evaluate THR-149 Treatment for Diabetic Macular Oedema (KALAHARI)
Clinicaltrials.gov Identifier: NCT04527107
Sponsor: Oxurion
Purpose: This study is conducted to select the THR-149 dose level and to assess the efficacy and safety of the selected dose level compared to aflibercept.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 122
Inclusion Criteria: Written informed consent obtained from the subject prior to screening procedures. Male or female aged 18 years or older at the time of signing the informed consent. Type 1 or type 2 diabetes. BCVA ETDRS letter score ≤ 73 and ≥ 39 in the study eye. Central involved DME (CI-DME) with CST of ≥ 320µm in men or ≥ 305µm in women, on spectral domain optical coherence tomography (SD-OCT), in the study eye. Received ≥ 5 anti-vascular endothelial growth factor (anti-VEGF) injections for the treatment of CI-DME. BCVA ETDRS letter score ≥ 34 in the fellow eye.
Exclusion Criteria: Macular edema due to causes other than DME in the study eye. Concurrent disease in the study eye, other than central-involved DME, that could require medical or surgical intervention during the study period or could confound interpretation of the results. Any condition that could confound the ability to detect the efficacy of the investigational medicinal product. Previous confounding medications/interventions, or their planned administration. Presence of neovascularisation at the disc in the study eye. Presence of iris neovascularisation in the study eye. Uncontrolled glaucoma in the study eye. Any active or suspected ocular or periocular infection, or active intraocular inflammation, in either eye. untreated diabetes mellitus. Glycated haemoglobin A (HbA1c) >12%. Uncontrolled hypertension.
Information: info@oxurion.com
Study: Study of a High-Dose Aflibercept in Participants With Diabetic Eye Disease (PHOTON)
Clinicaltrials.gov Identifier: NCT04429503
Sponsor: Regeneron Pharmaceuticals
Purpose: The primary objective of the study is to determine if treatment with high-dose aflibercept (HD) at intervals of 12 or 16 weeks provides non-inferior best corrected visual acuity (BCVA) compared to aflibercept dosed every 8 weeks.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 640
Inclusion Criteria: Diabetic macular edema (DME) with central involvement in the study eye. Best corrected visual acuity (BCVA) early treatment diabetic retinopathy study (ETDRS) letter score of 78 to 24 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye with decreased vision determined to be primarily the result of DME. Willing and able to comply with clinic visits and study-related procedures. Provide informed consent signed by study participant or legally acceptable representative.
Exclusion Criteria: Evidence of macular edema due to any cause other than diabetes mellitus in either eye. Active proliferative diabetic retinopathy in the study eye. IVT anti-VEGF treatment (aflibercept, ranibizumab, bevacizumab, brolucizumab, pegaptanib sodium) or panretinal laser photocoagulation (PRP) /macular laser photocoagulation within 12 weeks (84 days) or intraocular or periocular corticosteroids within 16 weeks (112 days) of the screening visit in the study eye. Prior IVT investigational agents in either eye (eg, anti-ang-2/anti-VEGF bispecific monoclonal antibodies, gene therapy, etc.) at any time. Treatment with ocriplasmin (JETREA®) in the study eye at any time. NOTE: other protocol defined inclusion/exclusion criteria apply.
Information: clinicaltrials@regeneron.com
Study: A Multicenter, Randomized Study in Participants With Diabetic Retinopathy Without Center-involved Diabetic Macular Edema To Evaluate the Efficacy, Safety, and Pharmacokinetics of Ranibizumab Delivered Via the Port Delivery System Relative to the Comparator Arm (PAVILION)
Clinicaltrials.gov Identifier: NCT04503551
Sponsor: Hoffmann-La Roche
Purpose: Study GR41675 is a multicenter, randomized study in participants with diabetic retinopathy without center-involved diabetic macular edema to evaluate the efficacy, safety of the port delivery system with ranibizumab (PDS) relative to the comparator arm.
Design: Randomized, parallel assignment, single masking
Number of Patients: 160
Inclusion Criteria: Age ≥18 years at time of signing informed consent form. Documented diagnosis of diabetes mellitus (Type 1 or Type 2). HbA1c level of ≤12% within 2 months prior to screening or at screening. Inclusion criteria for study eye. Moderately severe or severe NPDR (ETDRS-DRSS level 47 or 53). BCVA score of ≥ 69 letters (20/40 approximate Snellen equivalent or better).
Exclusion Criteria: Ocular exclusion criteria for study eye: Presence of center-involved diabetic macular edema (defined as CST ≥325 µm); Any intravitreal anti-VEGF treatment at any time prior to randomization; Any use of medicated intraocular implants, including Ozurdex or Iluvien implants at any time prior to randomization; Any intravitreal corticosteroid treatment at any time prior to randomization; Any periocular (eg, subtenon) corticosteroid treatment at any time prior to randomization; Any PRP at any time prior to randomization; Any macular laser photocoagulation (such as micropulse and focal or grid laser) at any time prior to randomization; Active intraocular inflammation (grade trace or above); Clinically significant abnormalities of the vitreous-retinal interface involving the macular area or disrupting the macular architecture, such as vitreous-retinal traction or epiretinal membrane (assessed by the investigator and confirmed by the central reading center); Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a participant's participation in the study; History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery; Any concurrent ocular condition (e.g., cataract, epiretinal membrane) that would require surgical intervention during the study to prevent or treat visual loss that might result from that condition; Any concurrent ocular condition (e.g., amblyopia, strabismus) that may affect interpretation of study results; History of other ocular diseases that gives reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, that might affect interpretation of study results, or that renders the participant at high risk for treatment complications. Ocular exclusion criteria for either eye: Suspected or active ocular or periocular infection of either eye; Any history uveitis including idiopathic, drug-associated or autoimmune-associated uveitis.
Information: global.rochegenentechtrials@roche.com
Study: Comparative Study of Dexamethasone Implant to Intravitreal Aflibercept in Subjects With Diabetic Macular Edema (PRECISION)
Clinicaltrials.gov Identifier: NCT04411693
Sponsor: The Cleveland Clinic
Purpose: This study is an interventional, prospective randomized study comparing the dexamethasone implant to intravitreal aflibercept. Subjects will have an initial single injection of aflibercept and will be randomized if diabetic macular edema persists. Each subject will be evaluated for 6 months following randomization. Thus, the study duration will be 12 months plus the recruitment period.
Design: Randomized, parallel assignment, no masking
Number of Patients: 50
Inclusion Criteria: Signed informed consent. Men and women ≥ 18 years of age. Foveal-involving retinal edema secondary to DME based on investigator review of SD-OCT. Central subfield thickness on SDOCT of greater than or equal to 325 microns on Spectralis or 300 microns on Cirrus. E-ETDRS best-corrected visual acuity of 20/400 or better in the study eye. Willing, committed, and able to return for ALL clinic visits and complete all study related procedures. Able to read, (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member) understand and willing to sign the informed consent form.
Exclusion Criteria: Any prior or concomitant therapy with another investigational agent to treat DME in the study eye. Prior panretinal photocoagulation in the study eye. Prior intravitreal anti-VEGF therapy in the study eye. Prior focal/grid laser photocoagulation in the study eye. Prior history of intravitreal steroid therapy in the study eye. Any history of severe allergy to fluorescein sodium (e.g., anaphylaxis, difficulty breathing) or other reason that the patient is unable to undergo fluorescein angiography (e.g., inability to get vascular access, unable to tolerate procedure). If allergy is mild and investigator believes can be pretreated with diphenhydramine to avoid allergic response, this is not an exclusion to enrollment. Uncontrolled glaucoma at baseline evaluation (defined as intraocular pressure ≥25 mmHg despite treatment with anti-glaucoma medication) in the study eye and/or cup-to-disc ratio greater or equal to 0.8. Active intraocular inflammation in either eye. Active ocular or periocular infection in either eye. Torn or ruptured posterior lens capsule in study eye. Laser capsulotomy is not a contraindication. Prior systemic anti-VEGF therapy, investigational or FDA-approved, is only allowed up to 3 months prior to first dose, and will not be allowed during the study. Significant vitreous hemorrhage obscuring view to the macula or the retinal periphery as determined by the investigator on clinical exam and ultra-widefield angiography, in study eye. Presence of other causes of macular edema, including pathologic myopia (spherical equivalent of -8 diopters or more negative, or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, choroidal neovascularization, age-related macular degeneration or multifocal choroiditis in the study eye. Epiretinal membranes are allowed. Presence of macula-threatening traction retinal detachment in the study eye. Prior vitrectomy in the study eye. History of retinal detachment or treatment or surgery for retinal detachment in the study eye. Any history of macular hole of stage 2 and above in the study eye. Any intraocular or periocular surgery within 3 months of day 1 in the study eye, except lid surgery, which may not have taken place within 1 month of day 1, as long as it's unlikely to interfere with the injection. Prior trabeculectomy or other filtration surgery in the study eye. Any ocular or periocular infection within the last 2 weeks prior to Screening in either eye. Any history of uveitis in either eye. Active scleritis or episcleritis in either eye. Presence or history of scleromalacia in either eye. Aphakia in the study eye. Previous therapeutic radiation in the region of the study eye. History of corneal transplant or corneal dystrophy in the study eye. Significant media opacities, including cataract, in the study eye which might interfere with visual acuity, assessment of safety, or fundus photography. Any concurrent intraocular condition in the study eye (eg, cataract) that, in the opinion of the investigator, could require either medical or surgical intervention during the study period. Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the subject beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety. Participation as a subject in any clinical study within the 12 weeks prior to day 1. Any systemic therapy with an investigational agent in the past 3 months prior to day 1. Any history of allergy to povidone iodine. Pregnant or breast-feeding women Women of childbearing potential* who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly) *Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
Information: ehlersj@ccf.org
Study: ADVM-022 Intravitreal Gene Therapy for DME (INFINITY)
Clinicaltrials.gov Identifier: NCT04418427
Sponsor: Adverum Biotechnologies, Inc.
Purpose: A phase 2, multicenter, randomized, double-masked, active controlled study of ADVM-022 (AAV.7m8-aflibercept) in subjects with diabetic macular edema.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 33
Inclusion Criteria: Age ≥18. Type 1 or type 2 diabetes mellitus. Willing and able to provide informed consent. Vision impairment due to center involving diabetic macular edema.
Exclusion Criteria: Uncontrolled diabetes defined as HbA1C >10%, or history of diabetic ketoacidosis within 3 months prior to randomization; or subjects who, within the last 3 months, initiated intensive insulin treatment (a pump or multiple daily injection) or plan to do so in the next 3 months. Acute coronary syndrome, myocardial infarction or coronary artery revascularization, CVA, TIA in the last 6 months. Uncontrolled hypertension defined as average SBP ≥160 mmHg or an average DBP ≥100 mmHg. Known severe renal impairment. High risk proliferative diabetic retinopathy. History of retinal disease in the study eye other than diabetic retinopathy. History of retinal detachment (with or without repair) in the study eye. History of vitrectomy, trabeculectomy, or other filtration surgery in the study eye. Any prior focal or grid laser photocoagulation or any prior PRP in the study eye. Current or planned pregnancy or breastfeeding.
Information: hjividen@adverum.com
Study: This Study Will Evaluate the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System with Ranibizumab (PDS) in Participants with Diabetic Macular Edema (DME) Compared with Intravitreal Ranibizumab (Pagoda)
Clinicaltrials.gov Identifier: NCT04108156
Sponsor: Hoffmann-La Roche
Purpose: This study will evaluate the efficacy, safety, and pharmacokinetics of the PDS in participants with diabetic macular edema (DME) when treated every 24 weeks (Q24W) compared with intravitreal ranibizumab 0.5 mg every 4 weeks (Q4W).
Design: Randomized, parallel assignment, single masking
Number of Patients: 545
Inclusion Criteria: Age ≥18 years at time of signing Informed Consent Form. Documented diagnosis of diabetes mellitus (Type 1 or Type 2). HbA1c level of ≤10% within 2 months prior to screening or at screening. Study eye: Macular thickening secondary to DME involving the center of the fovea with CST ≥325 um on SD-OCT at screening. BCVA of ≥25 letters.
Exclusion Criteria: High-risk proliferative diabetic retinopathy. Active intraocular inflammation (grade trace or above). Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis of either eye. Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient's participation in the study. Cerebrovascular accident or myocardial infarction within 6 months prior to randomization. Atrial fibrillation diagnosis or worsening within 6 months prior to randomization. Uncontrolled blood pressure.
Information: global-roche-genentech-trials@gene.com
Study: Efficacy and Safety of Brolucizumab vs Aflibercept in Patients with Visual Impairment Due to Diabetic Macular Edema (DME)
Clinicaltrials.gov Identifier: NCT03917472
Sponsor: Novartis Pharmaceuticals
Purpose: The purpose of this study is to evaluate the efficacy and safety of brolucizumab vs. aflibercept in the treatment of patients with visual impairment due to DME.
Design: Randomized, parallel assignment, triple masking
Number of Patients: 500
Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Patients with type 1 or type 2 diabetes mellitus (DM) and Hemoglobin A1c (HbA1c) ≤ 12% at screening. Study eye: Visual impairment due to DME with: Best-corrected visual acuity (BCVA) score between 73 and 23 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters. DME involving the center of the macula, with Central Subfield Thickness (CSFT) ≥ 320 µm on Spectral Domain Optical Coherence Tomography (SD-OCT).
Exclusion Criteria: High-risk proliferative diabetic retinopathy (PDR) in the study eye. Concomitant conditions or ocular disorders in the study eye which confound interpretation of study results, compromise visual acuity or require medical or surgical intervention. Any active intraocular or periocular infection or active intraocular inflammation in the either eye. Uncontrolled glaucoma in the study eye. Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA <20/200. Use of anti-VEGF therapies, intraocular surgery or laser photocoagulation (macular or panretinal) in the study eye during the 3-month period prior to baseline. Use of intraocular or periocular corticosteroids in the study eye during the 6-month period prior to baseline and use of fluocinolone acetonide intravitreal (IVT) implant (Iluvien) at any time prior to baseline. Prior investigational drugs in either eye, vitreoretinal surgery in the study eye at any time prior to baseline.
Information: novartis.email@novartis.com
Study: The Study to YD312 Tablet in Patients with Diabetic Macular Edema
Clinicaltrials.gov Identifier: NCT03635814
Sponsor: YD Global Life Science Co., Ltd.
Purpose: This study objectives is to evaluate the efficacy of YD312 to improve visual acuity in patients with diabetic macular edema (DME) compared to placebo and determine optimal dose of phase 2b study.
Design: Randomized, parallel assignment
Number of Patients: 100
Inclusion Criteria: Subject who is male or female ≥19 years of age. Subject who has a diagnosis of Type 1 or 2 diabetes. Subject who has study eye with definite retinal thickening due to diabetic macular edema involving the center of the macula. Subject who has voluntarily signed an informed consent form. Randomization Inclusion Criteria: Study eye must be eligible for the following criteria at randomization: Subject who has study eye with central subfield thickness (CST) of ≥300 μm on optical coherence tomography (OCT). Subject who has study eye with an early treatment diabetic retinopathy study (ETDRS) best-corrected visual acuity (BCVA) letter score ranging from 39 to 78, inclusive (approximate Snellen equivalent of 20/32 - 20/160).
Exclusion Criteria: Subject who has study eye with any of the following criteria: Subject whose primary cause of macular edema is non-diabetic disease/condition (eg, cataract extraction, vitreomacular interface abnormalities). Subject who is expected to have no improvement of decreased visual acuity in the opinion of investigator, even if macular edema is resolved (eg, foveal atrophy, abnormal pigmentation, dense subfoveal hard exudate). Subject who has proliferative diabetic retinopathy. Subject who took the following within 3 months before randomization: Focal/grid laser photocoagulation, Intravitreal/circumbulbar corticosteroid, anti-VEGF and pro-VEGF (but, no wash-out period is required for the corticosteroid eyedrops). Subject who took panretinal photocoagulation (PRP) or intravitreal dexamethasone implant within 6 months before randomization. Subject who has a history of vitrectomy. Subject who took major ophthalmic surgeries (all intraocular surgeries including cataract extraction and scleral buckle) within 6 months before randomization. Subject who had systemic treatment of corticosteroid or anti-VEGF within 3 months before randomization. Subject who administered vaccinium myrtillus extract or dobesilate calcium within 2 weeks before randomization. Subject who is suspected to require administration/treatment of drug/procedure that may affect the efficacy evaluation before the participation of clinical trial or during clinical trial (refer to '10.4 Combination Therapy and Contraindication'). Subject who has the following illness or abnormal laboratory test values: Subject who has a hypersensitivity to any excipients of the investigational product or similar class of drug and ingredient. Subject who has uncontrolled hypertension (SBP >160 mmHg or DBP >100 mmHg). Subject who has uncontrolled diabetes (HbA1c >10.0%). Subject who has uncontrolled glaucoma in either eye (intraocular pressure (IOP) >24 mmHg on medication or according to the investigator's judgment). ANC <1.5 × 109/L. Platelet <125 × 109/L. Total bilirubin >1.5 × ULN. AST or ALT >2 × ULN. Clcr* <40 mL/min. * Clcr (Cockcroft-Gault formula). = [(140 - age) x weight(kg) (x 0.85 for females)] / [72 x serum creatinine (Scr) (mg/dL)]. Severe heart failure (NYHA class III/IV). Malignant tumor within 5 years before randomization. Subject who is known to be HIV positive, is active hepatitis B patient or carrier, or is hepatitis C patient. Ocular inflammatory diseases such as uveitis, conjunctivitis, and blepharitis in either eye. However, the participation of subject in this study is considered at the discretion of investigator. Unstable angina, myocardial infarction, transient ischemic attack, cerebral infarction, coronary artery bypass surgery, or transluminal coronary angioplasty within 6 months before screening. Pregnant woman, lactating woman, or female or male subject of childbearing potential. *hormonal contraceptives, intrauterine contraceptive device, sterilization of spouse (eg, vasectomy, tubal ligation), double-barrier method (eg, combinational use of spermicides and condoms, diaphragm, contraceptive sponge, of FemCap). Subject who took administration/procedure of other investigational products or medical devices within longer period between 30 days before screening or over 5time half-life. Subject, at the discretion of the investigator, who is unsuitable to participate in the study.
Study: A Study Assessing AR-13503 Implant Alone and in Combination with Aflibercept in Subjects With nAMD or DME
Clinicaltrials.gov Identifier: NCT03835884
Sponsor: Aerie Pharmaceuticals
Purpose: First-in-human study of the safety of AR-13503 sustained release intravitreal implant in subjects with neovascular age-related macular degeneration (nAMD) and subjects with diabetic macular edema (DME).
Design: Randomized, sequential assignment, single
Number of Patients: 102
Inclusion Criteria: Inclusion Criteria for Subjects with Neovascular Age-Related Macular Degeneration (nAMD) or Diabetic Macular Edema (DME): 50 years of age or older. Presence of active subfoveal or juxtafoveal Choroidal Neovascularization (CNV) (any subtype) with leakage affecting the fovea secondary to AMD. Best corrected visual acuity (BCVA) in the study eye at Baseline (day 0): Stage 1: between 65 and 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/50 and 20/640 Snellen equivalent) Stage 2: between 65 and 20 ETDRS letters (20/50 and 20/400 Snellen equivalent). Able and willing to give signed informed consent and follow study instructions. Inclusion Criteria for Subjects with DME: Subjects with diabetic macular edema (DME) must meet all the following criteria to enter into the Study: 18 years of age or older. Type 1 or 2 diabetes mellitus with center-involved DME. BCVA in the study eye at Baseline (day 0): Stage 1: between 65 and 10 ETDRS letters (20/50 and 20/640 Snellen equivalent) Stage 2: between 65 and 20 ETDRS letters (20/50 and 20/400 Snellen equivalent). Able and willing to give signed informed consent and follow study instructions.
Exclusion Criteria: Exclusion criteria for subjects with neovascular age-related macular degeneration (nAMD): Ophthalmic: Use of intravitreal aflibercept within 8 weeks, ranibizumab or bevacizumab within 6 weeks. History of vitreoretinal surgery in the study eye. Any ocular disease in the study eye that in the Investigator and reading center's opinion may confound assessment of the macula, affect central vision, confound results, or preclude improvement in visual acuity. Any current or history of periocular or intraocular inflammation or evidence of infection in either eye. Media clarity insufficient to obtain quality fundus and OCT images in the study eye. Systemic: History or current systemic condition that in the Investigator opinion preclude the safe administration of the study treatment or confound results. History of allergy or sensitivity to fluorescein or povidone iodine. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. Participation in an investigational study within 30 days of Screening. Exclusion Criteria for Subjects with DME: Ophthalmic: Use of intraocular or periocular corticosteroids within 6 months, aflibercept within 8 weeks, ranibizumab or bevacizumab within 6 weeks. History of vitreoretinal surgery in the study eye. High risk proliferative diabetic retinopathy in the study eye and related complications. Structural damage to the center or the macula that is likely to preclude improvement in visual acuity in the study eye after resolution of the DME. Media clarity insufficient to obtain quality fundus and OCT images in the study eye. Systemic: History or current medical condition that in the Investigator's opinion preclude the safe administration of the study treatment or confound results. History of allergy or sensitivity to fluorescein or povidone iodine. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. Participation in an investigational study within 30 days of Screening.
Information: nramirez@aeriepharma.com, pbraswell@aeriepharma.com
Study: A Phase 1 Study of Episcleral Dexamethasone for Treatment of Macular Edema
Clinicaltrials.gov Identifier: NCT04005430
Sponsor: Targeted Therapy Technologies, LLC
Purpose: This phase 1 trial will assess primarily the safety and secondarily anti-inflammatory effect of Episcleral Dexamethasone in patients suffering from refractory diabetic macular edema.
Design: Single group assignment, no masking
Number of Patients: 3
Inclusion Criteria: Type I or II diabetes; age ≥18 years; visual acuity letter score in study eye <70 and ≥25 letters (approximate Snellen equivalent 20/32 to 20/320); ophthalmoscopic evidence of center-involved DME, within the central subfield (CSF); OCT CSF thickness value (microns): Zeiss Cirrus: ≥290 in women; ≥305 in men; Heidelberg Spectralis: ≥305 in women; ≥320 in men; Previous treatment with laser, anti-VEGF therapy and/or intravitreal steroids; No previous history of glaucoma or steroid-induced intraocular pressure response in either eye.
Exclusion Criteria: History of chronic renal failure requiring dialysis or kidney transplant; Retinal or optic nerve neovascularization on clinical exam, fundus photographs, or fluorescein angiograms; Evidence of external ocular infection; History of open-angle glaucoma or intraocular pressure ≥25 mmHg; History of steroid-induced IOP elevation that required IOP-lowering treatment; History of prior herpetic ocular infection; History of intravitreal or periocular corticosteroids within 3 months prior to enrollment; History of macular laser photocoagulation within 4 months prior to enrollment; History of antiangiogenic therapy within 4 weeks prior to enrollment; History of panretinal photocoagulation (PRP) within 4 months prior to enrollment or anticipated need for PRP in the next 6 months following enrollment; Presence of vitreomacular traction, epiretinal membrane, tractional retinal detachment, vitreous hemorrhage and or any ocular condition that the investigator judges could interfere in the safety and efficacy assessments; No other major non-diabetic pathology, or anticipation of such in the next 6 months following enrollment that in the opinion of the investigator would substantially and adversely affect assessment of safety and toxicity during the study; Participation in another clinical trial of non-approved medical treatment within 3 months prior to enrollment; Degenerative myopia; Malignant intraocular disease; Inability to understand informed consent, cooperate with testing or return to follow-up visits; Pregnant or lactating women; Co-existent ocular disorder of the cornea, lens or media that will interfere with assessment of safety or efficacy.
Information: Novartis.email@novartis.com
Study: Multiple Dose Safety and Efficacy of LKA651 in Patients with Diabetic Macular Edema
Clinicaltrials.gov Identifier: NCT03927690
Sponsor: Novartis Pharmaceuticals
Purpose: To evaluate the safety and efficacy of LKA651 in patients with macular edema from diabetic macular edema (DME).
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 90
Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Male and female patients age 18 to 85 years of age inclusive at screening. Presence of type I or type II diabetes mellitus. The ETDRS letter score in the study eye must be between 24 and 70 letters (approximate Snellen equivalent of 20/40-20/320). The non-study eye (fellow eye) should be ≥34 letters or better (approximate Snellen equivalent of 20/200) at screening. Presence of DME in the study eye, with decrease in vision due to foveal thickening of central macular thickness ≥320 µm in the central subfield, as assessed on SD-OCT and confirmed by the central reading center at screening.
Information: Novartis.email@novartis.com
Study: The Use of a Combination of Ozurdex and Eylea Versus Eylea Monotherapy for Diabetic Macular Edema: A Prospective, Comparative Trial (COED Trial)
Clinicaltrials.gov Identifier: NCT03984110
Sponsor: Texas Retina Associates
Purpose: The Use of a Combination of Ozurdex and Eylea Versus Eylea Monotherapy for Diabetic Macular Edema.
Design: Randomized, single group assignment, no masking
Number of Patients: 50
Inclusion Criteria: Type 1 or 2 diabetic patients; At least 18 years of age, understands the language of the informed consent, and is willing and able to provide written informed consent before any study procedures; Pseudophakic or phakic lens status with intact posterior lens capsule and/or Nd:YAG laser capsulotomy that in the investigator's opinion is not likely to permit dislocation of Ozurdex implant into the anterior chamber; Center-involving DME >300 µm; Baseline BCVA between 20/40 - 20/320; Eyes with intraocular pressure (IOP) ≤21 and / or treatment with <2 topical IOP-lowering medications (eyes with history of previous angle -closure or similar conditions that have been successfully treated with either laser or surgical intervention are allowed as long as the visual fields and optic nerves have been stable for >1 year prior to study entry and the patient has been and can be safely dilated).
Exclusion Criteria: Patients with active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases. Patients with known hypersensitivity to any components of Eylea or Ozurdex; Patient has suffered from a stroke or transient ischemic attack (TIA) in the last 6 months; Patients using topical anti-inflammatory medication for the duration of the study; Patients with ACIOL (anterior chamber intraocular lens) and rupture of the posterior lens capsule; Prior panretinal photocoagulation or macular laser treatments within 90 days of screening; Previous vitrectomy; Any ocular condition that in the opinion of the investigator would not permit improvement of visual acuity with resolution of DME (eg, foveal atrophy, pigment abnormalities, dense subfoveal hard exudates and/or poor foveal architecture suggestive of photoreceptor loss); Patients with retinal diseases other than diabetes that can affect macular edema; Eyes with a history of advanced glaucoma (optic nerve head change consistent with glaucoma damage and/or glaucomatous visual field loss), uncontrolled ocular hypertension (baseline IOP >21 mmHg despite use of ≥2 topical IOP-lowering medication); Eyes with a history of steroid response (ie, increase of ≥5 mmHg IOP following topical steroid treatment); Female patients who are pregnant or breastfeeding; Patients who are unable to attend scheduled follow-up visits throughout the 24-week study; Any intravitreal anti-VEGF treatment to study eye within 3 months prior to day 1; Use of systemic steroid, anti-VEGF or pro-VEGF treatment within 4 months prior to enrollment or anticipated use during the study (these drugs are prohibited from use during the study); History of any previous treatment in the study eye with an ocular corticosteroid implant (eg, Iluvien, Ozurdex, Retisert); Has scarring from laser photocoagulation in the study eye that would compromise VA; or scarring or abnormality from other macular condition, in the investigator's medical judgement, would limit VA (such as an epiretinal membrane or macular hole); Has significant media opacity precluding evaluation of retina and vitreous in the study eye. This includes cataract that is felt to be a major contributor to reduced visual acuity and/or likely to undergo surgical repair within 3 months of randomization. Has any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude participation in the study (eg, infection, uncontrolled elevated blood pressure, cardiovascular disease, poor glycemic control) or put the subject at risk due to study treatment or procedures; Has had a myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 1 month before enrollment.
Information: kduignan@texasretina.com, sarceneaux@texasretina.com
Study: Long Term Safety of Cooling Anesthesia for Intravitreal Injection (COOL-2)
Clinicaltrials.gov Identifier: NCT03956797
Sponsor: Recens Medical, Inc.
Purpose: The purpose of this clinical study is to evaluate the long term safety and efficacy of cooling anesthesia application to the eye as anesthesia for intravitreal injection using a novel cooling anesthesia device.
Design: Randomized, sequential assignment, no masking
Number of Patients: 60
Inclusion Criteria: Men and women >18 years old at screening visit. Men and women who are undergoing intravitreal injections in either 1 eye or both eyes with either Lucentis or Eylea as part of their normal standard of care with a 30-gauge needle. Subject has received a minimum of 3 intravitreal injections in the study eye prior to the study visit. Subject is willing and able to sign the study written informed consent form (ICF).
Exclusion Criteria: History of presence of scleromalacia; Preexisting conjunctival, episcleral or scleral defects; Less than 18 years of age; Unable to provide informed consent; Has received less than 3 injections in the study eye; Active severe eye disease not controlled with artificial tears and requiring Restasis or other prescription drugs for dry eye. History of Endophthalmitis with intravitreal injection; History of uveitis; History of retinal detachment in either eye; History of vitrectomy; Subjects who received administration of cooling anesthesia as part of the COOL-1 study will not be excluded and are eligible to participate in this study.
Information: arshad.khanani@gmail.com
Study: A Pilot Study Evaluating Photobiomodulation Therapy for Diabetic Macular Edema (AE)
Clinicaltrials.gov Identifier: NCT03866473
Sponsor: Jaeb Center for Health Research
Purpose: Randomized clinical trial evaluating the effect of photobiomodulation compared with sham on central subfield thickness (CST) in eyes with central-involved DME and good vision.
Design: Randomized, single group assignment
Number of Patients: 134
Inclusion Criteria: Age ≥18 years; Diagnosis of diabetes mellitus (type 1 or type 2). Any one of the following will be considered to be sufficient evidence that diabetes is present: Current regular use of insulin for the treatment of diabetes; Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes; Documented diabetes by American Diabetes Association and/or the World Health Organization criteria; Able and willing to provide informed consent. At least 1 eye meeting the following criteria: Best corrected E-ETDRS visual acuity letter score ≥79 (ie, 20/25 or better); Ophthalmoscopic evidence of central-involved DME, confirmed by CST on spectral domain OCT: Zeiss Cirrus: ≥290µm in women, and ≥305µm in men, Heidelberg Spectralis: ≥305µm in women, and ≥320µm in men; Media clarity, pupillary dilation, and study participant.
Exclusion Criteria: History of chronic renal failure requiring dialysis or kidney transplant. A condition that, in the opinion of the investigator, would preclude participation in the study (eg, unstable medical status that might preclude completion of follow-up). Initiation of intensive insulin treatment (a pump or multiple daily injections) within 4 months prior to randomization or plans to do so in the next 4 months. Participation in an investigational trial that involved treatment within 30 days of randomization with any drug/device that has not received regulatory approval for the indication being studied. Note: study participants cannot participant in another investigational trial that involves treatment with an investigational drug or device while participating in the study. Systolic blood pressure above 180 or diastolic blood pressure above 110. If blood pressure is brought below 180 systolic and 110 diastolic by anti-hypertensive treatment, individual can become eligible. Systemic anti-vascular endothelial growth factor (anti-VEGF) or pro-VEGF treatment within 4 months prior to randomization. These drugs should not be used during the study. For women of child-bearing potential: pregnant or intending to become pregnant within the next 8 months. Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed. Individual is expecting to move out of the area during the 8 months of the study. A participant will be excluded if the study eye meets any of the following criteria: Macular edema is considered to be due to a cause other than DME. An eye should not be considered eligible if: (1) the macular edema is considered to be related to ocular surgery such as cataract extraction or (2) clinical exam and/or investigator assessment of OCT suggests that vitreoretinal interface abnormalities (eg, a taut posterior hyaloid or epiretinal membrane) are contributing to the macular edema. An ocular condition is present such that, in the opinion of the investigator, any visual acuity loss would not improve from resolution of macular edema (eg, foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition). An ocular condition is present (other than DME) that, in the opinion of the investigator, might affect visual acuity during the course of the study or require intraocular treatment (eg, vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.) Cataract is present that, in the opinion of the investigator, may alter visual acuity during the course of the study. History of major ocular surgery (including cataract, scleral buckle, any intraocular surgery, etc.) within prior 4 months or major ocular surgery anticipated during the study period. Any history of prior laser or other surgical, intravitreal, or peribulbar treatment for DME or DR (such as panretinal photocoagulation, focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, or anti-VEGF) within the prior 12 months. If treatment was given more than 12 months prior, no more than 4 prior intraocular injections. Enrollment will be limited to a maximum of 15 percent of the planned sample size with any history of anti-VEGF treatment and a maximum of 15% with any history of PRP. Anticipated need to treat DME or DR during the study period. History of topical steroid or non-steroidal anti-inflammatory drug treatment within 30 days prior to randomization. History of YAG capsulotomy performed within 2 months prior to randomization. Any history of vitrectomy. Aphakia. Uncontrolled glaucoma.
Information: drcrnet@jaeb.org
Study: Micropulse for Suppression of Diabetic Macular Edema (PULSE)
Clinicaltrials.gov Identifier: NCT03519581
Sponsor: University of California, Davis; IRIDEX Corporation
Purpose: The purpose of this study is to determine if early intervention with micropulse laser treatment in eyes with good visual acuity (20/32 or better) will improve or stabilize vision loss due to the complications of diabetic macular edema.
Design: Randomized, parallel assignment, double masking
Number of Patients: 30
Inclusion Criteria: Age ≥18 years; Type 1 or type 2 diabetes mellitus; Clinical evidence of center-involved DME confirmed on OCT, and defined by OCT; Central Subfield (CSF) thickness at the time of randomization by the following: Zeiss Cirrus: 275μ in women, and 290μ in men; Heidelberg Spectralis: 290μ in women, and 305μ in men; Best corrected visual acuity of 20/32 or better on ETDRS testing.
Exclusion Criteria: Macular edema from causes other than DME; An ocular condition is present such that in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (ie, foveal atrophy, pigment abnormalities, dense hard exudates); An ocular condition is present other than DME which may contribute to macular edema (ie, vein occlusion, ERM, uveitis, RP). Cataract that in the opinion of the investigator may alter visual acuity throughout the course of the study; History of prior laser or other surgical, intravitreal, or peribulbar treatment for DME in the study eye within the prior 6 months. More than 4 prior intraocular injections for treatment of DME at any time; More than 1 prior focal/grid macular photocoagulation session for treatment of DME at any time; History of topical steroid or NSAID treatment within 30 days prior to randomization; History of PRP within 4 months prior to randomization or anticipated need for PRP in the 6 months following randomization. Any history of vitrectomy. History of major ocular surgery (cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization. History of YAG capsulotomy performed within 2 months prior to randomization. Aphakia. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.
Information: clwallace@ucdavis.edu
Study: Post Intravitreal Injection Topical NSAID vs Patching
Clinicaltrials.gov Identifier: NCT03918590
Sponsor: The New York Eye & Ear Infirmary
Purpose: A prospective randomized trial, to evaluate postinjection comfort measures comparing topical NSAID (nepafenac 0.3% suspension) and patching.
Design: Randomized, parallel assignment
Number of Patients: 60
Inclusion Criteria: 18 years of age or older; Already scheduled for anti-VEGF injection based on standard of care for disease process. Ability to provide written informed consent; Capable of complying with study protocol. Volunteer written informed consent with the understanding that consent may be withdrawn by the subject at any time without prejudice to future care.
Exclusion Criteria: History of past intraocular injection of steroid medication. Experiencing baseline eye pain; Monocular; non-study eye with VA<20/100. Unwilling or unable to follow or comply with all study related procedures.
Study: Steroid vs Anti-vascular Endothelial Growth Factor for Diabetic Macular Edema Prior to Phacoemulsification (STAMP)
Clinicaltrials.gov Identifier: NCT03832179
Sponsor: Bay Area Retina Associates
Purpose: The primary objective of this study is to compare the efficacy of antecedent intravitreal anti-vascular endothelial growth factor therapy vs Ozurdex in reducing postcataract surgery related macular edema in patients with pre-existing diabetic macular edema.
Design: Randomized, parallel assignment, no masking
Number of Patients: 32
Inclusion Criteria: Age >18 years of age; diagnosis of diabetes (Type 1 or 2) with a concomitant diagnosis of diabetic macular edema as demonstrated on spectral domain optical coherence tomography (Heidelberg Spectralis); >250 microns central foveal thickness; able and willing to provide informed consent.
Exclusion Criteria: Significant renal disease; a condition that in the opinion of the investigator would preclude participation; participation in another investigational trial within 30 days of randomization; application of focal macular laser within 120 days of enrollment; administration of Iluvien implant within 3 years of enrollment; administration of intravitreal triamcinolone within 3 months of enrollment; administration of any anti-vascular endothelial growth factor agent within 30 days of enrollment; known hypersensitivity to any of the investigational products; blood pressure >180/110; women who are pregnant, lactating, or intend to become pregnant within 1 year of randomization; vulnerable populations- including but not limited to wards of the state, cognitively impaired individuals, prisoners, institutionalized individuals; individual is planning on moving within 6 months of study enrollment; macular edema secondary to cause other than diabetic macular edema; ocular condition that, in the opinion of the investigators, may affect course of macular edema during course of study (vein occlusion, uveitis, etc.); evidence of ocular infections; evidence of uncontrolled glaucoma; known hypersensitivity to any components of bevacizumab, ranibizumab, aflibercept, or Ozurdex.
Information: cluo@bayarearetina.com, fahmed@bayarearetina.com
Study: Exploratory Study to Investigate the Bioactivity, Ocular and Systemic Safety, Tolerability, and Pharmacokinetics Following Single and Multiple Intravitreal Administrations of KSI-301 in Subjects With wAMD, DME and RVO
Clinicaltrials.gov Identifier: NCT03790852
Sponsor: Kodiak Sciences, Inc.
Purpose: This is a phase 1b open-label study to assess the bioactivity, ocular and systemic safety, tolerability, and pharmacokinetics of repeated injections of KSI-301 at 2 dose levels: 2.5 mg and 5 mg.
Design: Randomized, parallel assignment, no masking
Number of Patients: 50
Inclusion Criteria: DME Cohort: Treatment naïve diabetic macular edema. BCVA ETDRS letter score ≤78 and ≥23 (⁓20/25 to ⁓20/320 Snellen equivalent) in the study eye. Central subfield thickness (CST) of ≥300 microns on SD-OCT (Heidelberg Spectralis or equivalent). Decrease in vision in the study eye determined by the investigator to be primarily the result of DME.
Exclusion Criteria: DME Cohort: Initial diagnosis of DME of more than 6 months from screening in the study eye. Hard exudates in the fovea. Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant (dexamethasone or triamcinolone) in the study eye. Moderate or dense vitreous hemorrhage preventing clear. visualization of the macula or optic disc in the study eye. Fibrovascular proliferation or tractional retinal detachment in the posterior pole in the study eye. If traction is present outside the posterior pole, it should be considered not at risk of increasing and threatening the macula with the use of anti-VEGF injections, in the investigator's judgement.
Information: jehrlich@kodiak.com, pablovm@kodiak.com
Study: A Study to Evaluate the Efficacy and Safety of RO6867461 in Participants with Diabetic Macular Edema (RHINE)
Clinicaltrials.gov Identifier: NCT03622593
Sponsor: Hoffman-La Roche
Purpose: This study will evaluate the efficacy, safety, and pharmacokinetics of RO6867461 administered at 8-week intervals or as specified in the protocol following treatment initiation, compared with aflibercept once every 8 weeks (Q8W), in participants with diabetic macular edema (DME).
Number of Patients: 900
Design: Randomized, parallel assignment, triple masking
Inclusion Criteria: Type 1 or type 2 diabetes mellitus and hemoglobin A1c (HbA1c) of less than or equal to (≤) 10%. Macular thickening secondary to diabetic macular edema (DME) involving the center of the fovea. Decreased visual acuity attributable primarily to DME. Ability and willingness to undertake all scheduled visits and assessments. For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 3 months after the final dose of study treatment.
Exclusion Criteria: Currently untreated diabetes mellitus or previously untreated patients who initiated oral anti-diabetic medication or insulin within 3 months prior to day 1. Uncontrolled blood pressure, defined as a systolic value greater than (>)180 millimeters of mercury (mmHg) and/or a diastolic value >100 mmHg while a patient is at rest. Currently pregnant or breastfeeding, or intend to become pregnant during the study. Treatment with panretinal photocoagulation or macular laser within 3 months prior to day 1 to the study eye. Any intraocular or periocular corticosteroid treatment within the past 6 months prior to day 1 to the study eye. Prior administration of IVT RO6867461 in either eye. Active intraocular or periocular infection or active intraocular inflammation in the study eye. Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye. Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than DME in the study eye. Other protocol-specified inclusion/exclusion criteria may apply.
Information: global-roche-genentech-trials@gene.com
Study: A Study to Evaluate the Efficacy and Safety of RO6867461 in Participants with Diabetic Macular Edema (YOSEMITE)
Clinicaltrials.gov Identifier: NCT03622580
Sponsor: Hoffman-La Roche
Purpose: This study will evaluate the efficacy, safety, and pharmacokinetics of RO6867461 administered at 8-week intervals or as specified in the protocol following treatment initiation, compared with aflibercept once every 8 weeks (Q8W), in participants with diabetic macular edema (DME).
Number of Patients: 900
Design: Randomized, parallel assignment, triple masking
Inclusion Criteria: Type 1 or type 2 diabetes mellitus and hemoglobin A1c (HbA1c) of less than or equal to (≤) 10%. Macular thickening secondary to diabetic macular edema (DME) involving the center of the fovea. Decreased visual acuity attributable primarily to DME. Ability and willingness to undertake all scheduled visits and assessments. For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 3 months after the final dose of study treatment.
Exclusion Criteria: Currently untreated diabetes mellitus or previously untreated patients who initiated oral anti-diabetic medication or insulin within 3 months prior to day 1. Uncontrolled blood pressure, defined as a systolic value greater than (>)180 millimeters of mercury (mmHg) and/or a diastolic value >100 mmHg while a patient is at rest. Currently pregnant or breastfeeding, or intend to become pregnant during the study. Treatment with panretinal photocoagulation or macular laser within 3 months prior to day 1 to the study eye. Any intraocular or periocular corticosteroid treatment within the past 6 months prior to day 1 to the study eye. Prior administration of IVT RO6867461 in either eye. Active intraocular or periocular infection or active intraocular inflammation in the study eye. Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye. Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than DME in the study eye. Other protocol-specified inclusion/exclusion criteria may apply.
Information: global-roche-genentech-trials@gene.com
Study: Comparative Study to Evaluate the Efficacy and Safety of MYL-1701P and Eylea in Subjects with Diabetic Macular Edema
Clinicaltrials.gov Identifier: NCT03610646
Sponsor: Mylan Inc.
Purpose: Three hundred and twenty-four (324) eligible adult subjects with diabetes mellitus with central DME involvement will be randomized 1:1 to intravitreal treatment with MYL-1701P or Eylea.
Number of Patients: 324
Design: Randomized, parallel assignment, triple masking
Inclusion Criteria: Male or female subjects age ≥18 years. Subjects have type 1 or type 2 diabetes mellitus who present with central DME involvement in the study eye. The cause of decreased vision in the study eye has been attributed primarily to DME by the Investigator. Subject is able to understand and voluntarily provide written informed consent to participate in the study. If female of childbearing potential, the subject must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at baseline visit, and should not be nursing or planning a pregnancy. If female, subject must be: Surgically sterilized via hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or of childbearing potential and practicing an acceptable form of birth control (defined as the use of an intrauterine device; a barrier method, like condom, with spermicide; any form of hormonal contraceptives; or abstinence from sexual intercourse) starting 60 days prior to dosing and continuing at least 90 days following the last treatment. Of non-childbearing potential (ie, postmenopausal for at least 1 year). If male, subject must be surgically or biologically sterile. If not sterile, the subject must agree to use an acceptable form of birth control with sexual partner (as described in inclusion criteria #6b of protocol) or abstain from sexual relations during the study period and up to 90 days following the last treatment dose. Subject is willing to comply with the study duration, study visits and study related procedures.
Exclusion Criteria: Subjects with known hypersensitivity to aflibercept or any of the excipients. Subjects with current or planned use of systemic medications known to be toxic to the lens, retina or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines and ethambutol. Subjects with uncontrolled hypertension defined as systolic blood pressure >160 mmHg or diastolic blood pressure >95 mmHg. Subjects with a history of cerebrovascular accident or myocardial infarction within 6 months of randomization. Subjects who have only 1 functional eye, even if the eye met all other study requirements, or who have an ocular condition on the fellow eye with a poorer prognosis than the study eye.
Information: PrasannaC.Ganapathi@mylan.in
Study: Study of Efficacy and Safety of Brolucizumab vs Aflibercept in Patients with Visual Impairment Due to Diabetic Macular Edema (KESTREL)
Clinicaltrials.gov Identifier: NCT03481634
Sponsor: Novartis Pharmaceuticals
Purpose: The purpose of this study is to evaluate the efficacy and safety of brolucizumab in treatment of patients with visual impairment due to diabetic macular edema (DME).
Design: Parallel assignment, double masking
Number of Patients: 534
Inclusion Criteria: Written informed consent before any assessment; Patients with type 1 or type 2 diabetes mellitus and HbA1c of ≤10% at screening; Medication for the management of diabetes stable within 3 months prior to randomization and is expected to remain stable during the course of the study
Exclusion Criteria: Active proliferative diabetic retinopathy in the study eye; Active intraocular or periocular infection or active intraocular inflammation in study eye; Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) >25 millimeters mercury (mmHg); Previous treatment with anti-VEGF drugs or investigational drugs in the study eye; Stroke or myocardial infarction during the 6-month period prior to baseline; Uncontrolled blood pressure defined as a systolic value ≥160 mmHg or diastolic value ≥100 mmHg; Other protocol-specified inclusion/exclusion criteria may apply.
Information: novartis.email@novartis.com
Study: Phase 4 IOP Signals Associated with ILUVIEN (PALADIN)
Clinicaltrials.gov Identifier: NCT02424019
Sponsor: Alimera Sciences
Purpose: The specific objectives include the study of intraocular pressure (IOP) related data in patients who received ILUVIEN and how it relates to the patient's experiences following prior treatment with a course of corticosteroid which did not result in a clinically significant IOP elevation.
Design: Single group, no masking
Number of Patients: 153
Inclusion Criteria: Patients who are eligible for treatment with ILUVIEN based on the prescribing information.
Exclusion Criteria: Patients who are unable to understand and sign the informed consent form.
Study: DRCR.Net Aflibercept vs Bevacizumab + Deferred Aflibercept for the Treatment of CI-DME (DRCR AC)
Clinicaltrials.gov Identifier: NCT03321513
Sponsor: Jaeb Center for Health Research
Purpose: To compare the efficacy of intravitreous aflibercept with intravitreous bevacizumab + deferred aflibercept if needed in eyes with CI DME and moderate vision loss.
Design: Randomized, parallel assignment, double masking
Number of Patients: 260
Inclusion Criteria: Best corrected Electronic-Early Treatment Diabetic Retinopathy Study visual acuity letter score <69 (ie, 20/50 or worse) and ≥24 (ie, 20/320 or better) within 8 days of randomization. On clinical exam, definite retinal thickening due to diabetic macular edema involving the center of the macula. Diabetic macular edema present on optical coherence tomography (OCT) within 8 days of randomization; Zeiss Cirrus central subfield: ≥290µm in women or ≥305µm in men; Heidelberg Spectralis central subfield: ≥305µm in women or ≥320µm in men; investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality. Media clarity, pupillary dilation, and individual cooperation sufficient for adequate fundus photographs.
Exclusion Criteria: Macular edema is considered to be due to a cause other than diabetic macular edema. An eye should not be considered eligible if: (1) the macular edema is considered to be related to ocular surgery such as cataract extraction or (2) clinical exam and/or OCT suggest that vitreoretinal interface abnormalities (eg, a taut posterior hyaloid or epiretinal membrane) are the primary cause of the macular edema. An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema (eg, foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition). An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (eg, vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.). Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (ie, cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal). History of an anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in the past 12 months or history of any other treatment for DME at any time in the past 4 months (such as focal/grid macular photocoagulation, intravitreous or peribulbar corticosteroids). Enrollment will be limited to a maximum of 25% of the planned sample size with any history of anti-VEGF treatment for DME. Once this number of eyes has been enrolled, any history of anti-VEGF treatment for DME will be an exclusion criterion. History of panretinal photocoagulation within 4 months prior to randomization or anticipated need for panretinal photocoagulation in the 6 months following randomization. History of anti-VEGF treatment for a disease other than DME in the past 12 months. History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization. History of YAG capsulotomy performed within 2 months prior to randomization. Aphakia. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis. Evidence of uncontrolled glaucoma.
Study: Anti-VEGF Treatment for Prevention of PDR/DME
Clinicaltrials.gov Identifier: NCT02634333
Sponsor: Jaeb Center for Health Research
Purpose: To determine the efficacy and safety of intravitreous aflibercept injections vs sham injections (observation) for prevention of PDR or CI-DME in eyes at high risk for development of these complications.
Design: Randomized, Safety/Efficacy, Parallel Assignment, Double-Blind, Prevention
Number of Patients: 322
Inclusion Criteria: No evidence of neovascularization on clinical exam including active neovascularization of the iris (small iris tufts are not an exclusion) or angle neovascularization (if the angle is assessed); no evidence of neovascularization (NV) on fluorescein angiography within the 7-modified ETDRS fields, confirmed by the central Reading Center prior to randomization. The widest method of imaging available at the site must be used to document whether there is NV present in the periphery; however, presence of NV outside of the 7-modified ETDRS fields on ultrawide field imaging will not be an exclusion provided treatment is not planned; no center-involved diabetic macular edema (CI-DME) on clinical exam and optical coherence tomography (OCT) central subfield thickness must be below the following gender and OCT-machine specific thresholds.
Exclusion Criteria: Exam or photographic evidence of vitreous or preretinal hemorrhage presumed to be from PDR; history of prior vitreous hemorrhage or preretinal hemorrhage presumed to be from PDR; history of prior PRP (defined as ≥100 burns outside of the posterior pole); an ocular condition is present (other than diabetic retinopathy) that, in the opinion of the investigator, might alter visual acuity during the course of the study (eg, retinal vein or artery occlusion, uveitis or other ocular inflammatory disease, vitreomacular traction, etc.).
Information: www.jaeb.org
RETINAL VEIN OCCLUSION
NEW: Study: A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Macular Edema Secondary to Branch Retinal Vein Occlusion (BALATON)
Clinicaltrials.gov Identifier: NCT04740905
Sponsor: Hoffmann-La Roche
Purpose: This is a phase 3, multicenter, randomized, double-masked, active comparator-controlled, parallel-group study evaluating the efficacy, safety, and pharmacokinetics of faricimab administered by intravitreal (IVT) injection at 4-week intervals until Week 24, followed by a double-masked period of study without active control to evaluate faricimab administered according to a personalized treatment interval (PTI) dosing regimen in participants with macular edema due to branch retinal vein occlusion (BRVO).
Design: Randomized, parallel assignment, triple masking
Number of Patients: 570
Inclusion Criteria: Foveal center-involved macular edema due to branch retinal vein occlusion (BRVO), diagnosed no longer than 4 months prior to the screening visit. Best-corrected visual acuity (BCVA) of 73 to 19 letters, inclusive (20/40 to 20/400 approximate Snellen equivalent) on Day 1. Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm diagnosis. For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs during the treatment period and for 3 months after the final dose of study treatment.
Exclusion Criteria: Any major illness or major surgical procedure within 1 month before screening. Uncontrolled blood pressure. Stroke (cerebral vascular accident) or myocardial infarction within 6 months prior to Day 1. Pregnant or breastfeeding, or intending to become pregnant during the study. Ocular Exclusion Criteria for Study Eye: History of previous episodes of macular edema due to RVO or persistent macular edema due to RVO diagnosed more than 4 months before screening. Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than macular edema due to RVO in the study eye (e.g., ischemic maculopathy, Irvine-Gass syndrome, foveal atrophy, foveal fibrosis, pigment abnormalities, dense subfoveal hard exudates, or other non-retinal conditions). Macular laser (focal/grid) in the study eye at any time prior to Day 1. Panretinal photocoagulation in the study eye within 3 months prior to Day 1 or anticipated within 3 months of study start on Day 1. Any prior or current treatment for macular edema; macular neovascularization, including diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); and vitreomacular-interface abnormalities, including, but not restricted to, IVT treatment with anti-VEGF, steroids, tissue plasminogen activator, ocriplasmin, C3F8, air or periocular injection. Any prior intervention with verteporfin photodynamic therapy, diode laser, transpupillary thermotherapy, or vitreo-retinal surgery including sheatotomy. Any prior steroid implant use including dexamethasone intravitreal implant (Ozurdex) and fluocinolone acetonide intravitreal implant (Iluvien). Ocular Exclusion Criteria for Both Eyes: Prior IVT administration of faricimab in either eye. History of idiopathic or autoimmune-associated uveitis in either eye. Active periocular, ocular or intraocular inflammation or infection (including suspected) in either eye on Day 1.
Information: global-roche-genentech-trials@gene.com
NEW: Study: A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Macular Edema Secondary to Central Retinal or Hemiretinal Vein Occlusion (COMINO)
Clinicaltrials.gov Identifier: NCT04740931
Sponsor: Hoffmann-La Roche
Purpose: This is a Phase III, multicenter, randomized, double-masked, active comparator-controlled, parallel-group study evaluating the efficacy, safety, and pharmacokinetics of faricimab administered by intravitreal (IVT) injection at 4-week intervals until Week 24, followed by a double-masked period of study without active control to evaluate faricimab administered according to a personalized treatment interval (PTI) dosing regimen in patients with macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO).
Design: Randomized, parallel assignment, triple masking
Number of Patients: 750
Inclusion Criteria: Foveal center-involved macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO), diagnosed no longer than 4 months prior to the screening visit. Best-corrected visual acuity (BCVA) of 73 to 19 letters, inclusive (20/40 to 20/400 approximate Snellen equivalent). Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm diagnosis. For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs during the treatment period and for 3 months after the final dose of study treatment.
Exclusion Criteria: Any major illness or major surgical procedure within 1 month before screening. Uncontrolled blood pressure. Stroke (cerebral vascular accident) or myocardial infarction within 6 months prior to Day 1. Pregnant or breastfeeding, or intending to become pregnant during the study. Ocular Exclusion Criteria for Study Eye: History of previous episodes of macular edema due to RVO or persistent macular edema due to RVO diagnosed more than 4 months before screening. Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than macular edema due to RVO in the study eye (e.g., ischemic maculopathy, Irvine-Gass syndrome, foveal atrophy, foveal fibrosis, pigment abnormalities, dense subfoveal hard exudates, or other non-retinal conditions). Macular laser (focal/grid) in the study eye at any time prior to Day 1. Panretinal photocoagulation in the study eye within 3 months prior to Day 1 or anticipated within 3 months of study start on Day 1. Any prior or current treatment for macular edema; macular neovascularization, including diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); and vitreomacular-interface abnormalities, including, but not restricted to, IVT treatment with anti-VEGF, steroids, tissue plasminogen activator, ocriplasmin, C3F8, air or periocular injection. Any prior intervention with verteporfin photodynamic therapy, diode laser, transpupillary thermotherapy, or vitreo-retinal surgery including sheatotomy. Any prior steroid implant use including dexamethasone intravitreal implant (Ozurdex) and fluocinolone acetonide intravitreal implant (Iluvien). Ocular Exclusion Criteria for Both Eyes: Prior IVT administration of faricimab in either eye. History of idiopathic or autoimmune-associated uveitis in either eye. Active periocular, ocular or intraocular inflammation or infection (including suspected) in either eye on Day 1.
Information: global-roche-genentech-trials@gene.com
Study: A Study to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Patients With Macular Edema Due to Retinal Vein Occlusion (RVO) (BEACON)
Clinicaltrials.gov Identifier: NCT04592419
Sponsor: Kodiak Sciences Inc
Purpose: This phase 3 study will evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept, in participants with macular edema due to treatment-naïve branch (BRVO) or central retinal vein occlusion (CRVO).
Design: randomized, parallel assignment, triple masking
Number of Patients: 550
Inclusion Criteria: Signed informed consent prior to participation in the study. Treatment-naïve macular edema of 6 months duration or less due to CRVO or BRVO. Participants with hemiretinal vein occlusion will be included as CRVO. BCVA ETDRS letter score between 80 and 25 (20/25 to 20/320 Snellen equivalent), inclusive in the Study Eye. CST of ≥ 320 microns on SD-OCT (Heidelberg Spectralis or equivalent on other OCT instruments) as determined by the Reading Center. Decrease in vision determined by the Investigator to be primarily the result of ME secondary to RVO. Other protocol-specified inclusion criteria may apply.
Exclusion Criteria: Macular edema in the Study Eye for reasons other than RVO. Active iris or angle neovascularization, neovascular glaucoma, neovascularization of the optic disc, retinal neovascularization or vitreous hemorrhage in the Study Eye. Uncontrolled glaucoma in the Study Eye. Active retinal disease other than the condition under investigation in the Study Eye. Any history or evidence of a concurrent ocular condition present, that in the opinion of the Investigator could require either medical or surgical intervention alter visual acuity during the study. Active or suspected ocular or periocular infection or inflammation. Any prior use of an approved or investigational treatment for macular edema secondary to RVO in the Study Eye (e.g. anti-VEGF, intraocular or periocular steroids, macular laser photocoagulation). Women who are pregnant or lactating or intending to become pregnant during the study. Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥100 mmHg while at rest. Recent history (within the 6 months prior to screening) of myocardial infarction, stroke, transient ischemic attack, acute congestive heart failure or any acute coronary event. History of a medical condition that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product. Other protocol-specified exclusion criteria may apply.
Information: ksi301clinical@kodiak.com
Study: A 3-month Study to Assess the Safety of ONS-5010 in Subjects With Visual Impairment Due to Retinal Disorders
Clinicaltrials.gov Identifier: NCT04516278
Sponsor: Outlook Therapeutics, Inc.
Purpose: The study will evaluate the safety of ophthalmic bevacizumab in subjects diagnosed with a retinal condition that would benefit from treatment with intravitreal injection of bevacizumab, including: exudative age-related macular degeneration, diabetic macular edema, or branch retinal vein occlusion.
Design: Single group, no masking
Number of Patients: 180
Inclusion Criteria: Active clinical diagnosis and OCT confirmation of one of the following retinal disorders: exudative age-related macular degeneration (AMD), diabetic macular edema (DME), or branch retinal vein occlusion (BRVO) and, in the opinion of the Investigator, requires treatment with an anti-VEGF therapy.
Exclusion Criteria: Previous use of approved anti-VEGF or Avastin® within 4 weeks preceding randomization. Macular edema due to something other than exudative AMD, DME or BRVO, in the study eye. History of inadequate response to previous intravitreal anti-VEGF therapy. History of any intraocular or periocular corticosteroid injection or implant, in the study eye. Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within 1-month preceding randomization. Any concurrent intraocular condition in the study eye that may require medical or surgical intervention or contribute to vision loss during the study period. Active intraocular inflammation in the study eye. Current vitreous hemorrhage in the study eye. Polypoidal choroidal vasculopathy (PCV) in the study eye. History of idiopathic, infectious or autoimmune-associated uveitis in either eye. Current ocular or periocular infection, such as conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye. Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥30 mmHg despite treatment with anti-glaucoma medication). Premenopausal women not using adequate contraception. Current treatment for active systemic infection. Known allergy to any component of the study drug, not amenable to treatment.
Information: jenniferkissner@outlooktherapeutics.com
Study: Minocycline to Treat Branch Retinal Vein Occlusion
Clinicaltrials.gov Identifier: NCT01468831
Sponsor: National Eye Institute (NEI)
Purpose: To test the safety and effectiveness of minocycline as a treatment for branch retinal vein occlusion.
Design: Randomized, parallel assignment, double masking
Number of Patients: 7
Inclusion Criteria: For study eye: The study eye has a best-corrected ETDRS visual acuity score between 78 and 34 letters (i.e., between 20/32 and 20/200). The study eye shows evidence of definite retinal thickening due to a BRVO based on clinical examination involving the center of the macula that is not refractory to further therapy as based on the investigator s clinical judgment. BRVO is defined as an eye that had retinal hemorrhage or other biomicroscopic evidence of RVO (e.g., telangiectatic capillary bed) and a dilated (or previously dilated) venous system in one or two quadrants or less of the retina drained by the affected vein. Hemiretinal vein occlusion (HRVO) is an RVO that involves two altitudinal quadrants. In this study, eyes with a HRVO will be considered a BRVO and are given the same treatment as BRVO eyes. The study eye has retinal thickness in the central subfield on baseline OCT measurement >350 microns, as measured by Zeiss Cirrus spectral domain OCT, or an equivalent retinal thickness on a similar OCT machine. The study eye has media clarity and pupillary dilation sufficient for adequate fundus photographs. Furthermore, the participant must be able to cooperate during the procedure for accurate fundus photographs. Additional criteria at www.Clinicaltrials.gov .
Exclusion Criteria: For study eye: The macular edema is considered to be related to cataract extraction, or Clinical examination and/or OCT suggest that vitreoretinal interface disease (e.g., a taut posterior hyaloid or epiretinal membrane) is the primary cause of the macular edema, or Clinical examination, medical history and/or fluorescein angiography suggest that diabetic retinopathy is the primary cause of the edema. The study eye has a history of a recurrent RVO. The study eye has a history of RVO present for > 18 months. A brisk afferent pupillary defect (APD) is present in the study eye. An ocular condition is present in the study eye such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, laser scar at fovea, non-retinal condition). An ocular condition (other than RVO) is present that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc.). A substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by three lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal) is present in the study eye. The study eye has had panretinal or sectoral scatter photocoagulation (PRP) within four months prior to study entry. The study eye has had pars plana vitrectomy within six months prior to study entry. The study eye has undergone major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within three months prior to study entry. A yttrium aluminum garnet (YAG) capsulotomy has been performed on the study eye within two months prior to study entry. The study eye has had treatment < 3 months prior to study entry of intravitreal or periocular steroid injections. The study eye has had treatment < 28 days prior to study entry of intravitreal anti-VEGF agents.
Study: Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion (RAVEN)
Clinicaltrials.gov Identifier: NCT03810313
Sponsor: Novartis Pharmaceuticals
Purpose: The purpose of this study is to evaluate the efficacy and safety of brolucizumab in treatment of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO).
Design: Randomized, parallel assignment, triple masking
Number of Patients: 750
Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Patients with visual impairment due to ME secondary to CRVO diagnosed < 6 months prior to screening. BCVA score between 78 and 23 letters, inclusive, using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/32 to 20/320) at both screening and baseline visits.
Exclusion Criteria: Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g. structural damage of the fovea, vitreous hemorrhage, retinal vascular occlusion other than CRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema). Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline. Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator's judgment, at screening or baseline. Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 20/200 at screening (except when due to conditions whose surgery may improve VA, e.g. cataract). Previous treatment with any anti-VEGF therapy or investigational drugs in the study eye at any time prior to baseline. Previous use of intraocular or periocular steroids in study eye at any time prior to baseline. Macular laser photocoagulation (focal/grid) in the study eye at any time prior to baseline and peripheral laser photocoagulation in the study eye within 3 months prior to the baseline. Intraocular surgery in the study eye during the 3‑month period prior to baseline. Vitreoretinal surgery in the study eye at any time prior to baseline. Aphakia with the absence of posterior capsule in the study eye.
Information: novartis.email@novartis.com
Study: Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients With Visual Impairment Due to Macular Edema Secondary to Branch Retinal Vein Occlusion (RAPTOR)
Clinicaltrials.gov Identifier: NCT03802630
Sponsor: Novartis Pharmaceuticals
Purpose: The purpose of this study is to evaluate the efficacy and safety of brolucizumab in treatment of patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO).
Design: Randomized, parallel assignment, triple masking
Number of Patients: 500
Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Patients with visual impairment due to ME secondary to BRVO diagnosed < 6 months prior to screening. BCVA score between 78 and 23 letters, inclusive, using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/32 to 20/320) at both screening and baseline visits.
Exclusion Criteria: Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g. structural damage of the fovea, vitreous hemorrhage, retinal vascular occlusion other than BRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema). Hemiretinal vein occlusion should be excluded. Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline. Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator's judgment, at screening or baseline. Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 20/200 at screening (except when due to conditions whose surgery may improve VA, e.g. cataract). Previous treatment with any anti-VEGF therapy or investigational drugs in the study eye at any time prior to baseline. Previous use of intraocular or periocular steroids in study eye at any time prior to baseline. Macular laser photocoagulation (focal/grid) in the study eye at any time prior to baseline and peripheral laser photocoagulation in the study eye within 3 months prior to the baseline. Intraocular surgery in the study eye during the 3‑month period prior to baseline. Vitreoretinal surgery in the study eye at any time prior to baseline. Aphakia with the absence of posterior capsule in the study eye.
Information: novartis.email@novartis.com
Study: Phase 1 Study of Episcleral Celecoxib for Treatment of Macular Edema and Inflammatory Disorders of the Posterior Pole
Clinicaltrials.gov Identifier: NCT04120636
Sponsor: Targeted Therapy Technologies, LLC
Purpose: This phase 1 trial will assess primarily the safety and secondarily the anti-inflammatory and anti-neovascular effect of Episcleral Celecoxib in patients suffering from macular edema and other inflammatory disorders of the retina, choroid and vitreous.
Design: Single group, no masking
Number of Patients: 3
Inclusion Criteria: Age ≥18 years; Visual acuity letter score in study eye <70 and ≥25 letters (approximate Snellen equivalent 20/32 to 20/320); ophthalmoscopic evidence of center-involved macular edema, within the central subfield (CSF); inflammatory disorders of the sclera, choroid, retina or vitreous.
Exclusion Criteria: Inability to understand informed consent, cooperate with testing or return to follow-up visits; pregnant or lactating women; co-existent ocular disorder of the cornea, lens or media that will interfere with assessment of safety or efficacy.
Study: Episcleral Dexamethasone for Treatment of Macular Edema and Inflammatory Disorders of the Posterior Pole
Clinicaltrials.gov Identifier: NCT04120311
Sponsor: Targeted Therapy Technologies, LLC
Purpose: This phase 1 trial will assess primarily the safety and secondarily anti-inflammatory effect of Episcleral Dexamethasone in patients suffering from macular edema and other disorders of the retina, choroid and vitreous.
Design: Single group, no masking
Number of Patients: 3
Inclusion Criteria: Age ≥18 years; Visual acuity letter score in study eye <70 and ≥25 letters (approximate Snellen equivalent 20/32 to 20/320); ophthalmoscopic evidence of center-involved macular edema, within the central subfield (CSF); inflammatory disorders of the sclera, choroid, retina or vitreous.
Exclusion Criteria: Inability to understand informed consent, cooperate with testing or return to follow-up visits; pregnant or lactating women; co-existent ocular disorder of the cornea, lens or media that will interfere with assessment of safety or efficacy.
Study: Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients with Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion (RAVEN)
Clinicaltrials.gov Identifier: NCT03810313
Sponsor: Novartis Pharmaceuticals
Purpose: The purpose of this study is to evaluate the efficacy and safety of brolucizumab in treatment of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO).
Design: Randomized, parallel assignment, triple masking
Number of Patients: 750
Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Patients with visual impairment due to ME secondary to BRVO diagnosed <6 months prior to screening. BCVA score between 78 and 23 letters, inclusive, using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/32 to 20/320) at both screening and baseline visits.
Exclusion Criteria: Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (eg structural damage of the fovea, vitreous hemorrhage, retinal vascular occlusion other than BRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema). Hemiretinal vein occlusion should be excluded. Any active intraocular or periocular infection or active intraocular inflammation (eg infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline. Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) >25 mmHg on medication, or according to investigator's judgment, at screening or baseline. Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA <20/200 at screening (except when due to conditions whose surgery may improve VA, eg cataract). Previous treatment with any anti-VEGF therapy or investigational drugs in the study eye at any time prior to baseline. Previous use of intraocular or periocular steroids in study eye at any time prior to baseline. Macular laser photocoagulation (focal/grid) in the study eye at any time prior to baseline and peripheral laser photocoagulation in the study eye within 3 months prior to the baseline. Intraocular surgery in the study eye during the 3‑month period prior to baseline. Vitreoretinal surgery in the study eye at any time prior to baseline. Aphakia with the absence of posterior capsule in the study eye.
Information: novartis.email@novartis.com
Study: Treatment of Central Retinal Vein Occlusion Using Stem Cells Study (TRUST)
Clinicaltrials.gov Identifier: NCT03981549
Sponsor: The Emmes Company, LLC
Purpose: This study evaluates whether intravitreal autologous CD34+ stem cell therapy is safe, feasible and potentially beneficial in eyes with vision loss from central retinal vein occlusion (CRVO). Half of the participants will receive immediate cellular therapy followed by sham therapy 6 months later, while the other half will receive immediate sham therapy followed by cellular therapy 6 months later. Participants will be followed for a total of 2 years.
Design: Randomized, parallel assignment, triple masking
Number of Patients: 20
Inclusion Criteria: Clinical diagnosis of central retinal vein occlusion (CRVO) confirmed by review of medical records and screening assessment. Best Corrected Visual Acuity (BCVA) obtained during the screening period is in the range of 20/60+ to 20/400- (ETDRS letter score in the range of 18 to 63, inclusive). Duration of vision loss from CRVO ≥6 months to 3 years.
Exclusion Criteria: Previous eye treatment with intravitreal or periocular steroids, intravitreal injection, laser or intraocular surgery within 6 months prior to enrollment (ie, date ICF signed) or treatment expected during the study period. History of concurrent ocular herpes infection. Active non-herpetic eye infection diagnosed within 8 weeks from enrollment (ie, date Informed Consent Form (ICF) signed). Glaucoma requiring treatment with more than 1 medication, laser or intraocular surgery. Active uveitis or history of recurrent uveitis or uveitis involving the posterior segment. Presence of cataract that is impairing vision. Presence of lens or lens implant subluxation. History of ocular trauma that is currently impairing vision. History or concurrent optic nerve or retinal disease, including macular degeneration, myopic degeneration, retinitis pigmentosa, retinal tear or detachment. Active retinal or iris neovascularization. Macular edema requiring on-going therapy or where treatment is expected during the study period. Significant media opacity precluding view of the fundus for examination, photography or optical coherence tomography (OCT) including cataract and vitreous haze. High myopia (>9 diopters); Amblyopia; Other cause contributing to vision loss at screening. History of any of the following procedures: corneal transplant, glaucoma surgery, photodynamic therapy, retinal cryopexy, pneumatic retinopexy, intraocular oil or scleral buckle.
Information: dcmacias@ucdavis.edu, mesalvador@ucdavis.edu
Study: Post Intravitreal Injection Topical NSAID vs Patching
Clinicaltrials.gov Identifier: NCT03918590
Sponsor: The New York Eye & Ear Infirmary
Purpose: A prospective randomized trial, to evaluate postinjection comfort measures comparing topical NSAID (nepafenac 0.3% suspension) and patching.
Design: Randomized, parallel assignment
Number of Patients: 60
Inclusion Criteria: 18 years of age or older; Already scheduled for anti-VEGF injection based on standard of care for disease process. Ability to provide written informed consent; Capable of complying with study protocol. Volunteer written informed consent with the understanding that consent may be withdrawn by the subject at any time without prejudice to future care.
Exclusion Criteria: History of past intraocular injection of steroid medication. Experiencing baseline eye pain; Monocular; non-study eye with VA<20/100. Unwilling or unable to follow or comply with all study related procedures.
Study: Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2)
Clinicaltrials.gov Identifier: NCT01969708
Sponsor: The EMMES Corporation
Purpose: SCORE2 is a multicenter, prospective, randomized, phase III clinical trial in which all participants enrolled will be followed for up to 2.5 years. SCORE2 is designed as a non-inferiority trial, with study eyes randomized to intravitreal bevacizumab (1.25 mg) every 4 weeks vs intravitreal aflibercept (2.0 mg) every 4 weeks. SCORE2 aims to determine if bevacizumab is non-inferior to aflibercept for the treatment of macular edema associated with central retinal vein occlusion (CRVO), with the primary outcome of visual acuity measured at month 6.
Design: Randomized, parallel assignment, single masking
Number of Patients: 362
Inclusion Criteria: Participants must have center-involved macular edema secondary to CRVO. Eyes may be enrolled as early as the time of diagnosis of the macular edema. The definition of CRVO used in SCORE will also be used for the purposes of SCORE2: a CRVO is defined as an eye that has retinal hemorrhage or other biomicroscopic evidence of retinal vein occlusion (eg, telangiectatic capillary bed) and a dilated venous system (or previously dilated venous system) in all 4 quadrants. Due to the similarities of a hemiretinal vein occlusion (HRVO) to CRVO, HRVO will be classified as CRVO for the purposes of this clinical trial. Eyes classified as having a HRVO will be limited to no more than 25% of the planned sample size. A HRVO is defined as an eye that has retinal hemorrhage or other biomicroscopic evidence of retinal vein occlusion (eg telangiectatic capillary bed) and a dilated venous system (or previously dilated venous system) in 5 or more clock hours but less than all 4 quadrants. Typically, a HRVO is a retinal vein occlusion that involves 2 altitudinal quadrants. E-Early Treatment Diabetic Retinopathy Study (ETDRS)visual acuity score of greater than or equal to 19 letters (approximately 20/400) and less than or equal to 73 letters (approximately 20/40) by the ETDRS visual acuity protocol. The investigator must believe that a study eye with visual acuity between 19 and 33 letters is perfused. Retinal thickness on SD-OCT measurement, defined as central subfield thickness of 300 µm or greater. If the SD-OCT measurement is taken from a Heidelberg Spectralis Machine, the central subfield thickness should be 320 µm or greater. Media clarity, pupillary dilation and participant cooperation sufficient for adequate fundus photographs.
Exclusion Criteria: A condition that, in the opinion of the investigator, would preclude participation in the study (eg, chronic alcoholism or drug abuse, personality disorder or use of major tranquilizers indicating difficulty in long term follow-up, likelihood of survival of less than 12 months). Participation in an investigational trial within 30 days of study entry that involved treatment with any drug that has not received regulatory approval at time of study entry. History of allergy to any anti-VEGF agent, corticosteroid, or component of the delivery vehicle. The participant will be moving out of the area of the clinical site to an area not covered by another clinical site during the 12 months of the study. Positive urine pregnancy test: all women of childbearing potential (those who are premenopausal and not surgically sterilized) may participate only if they have a negative urine pregnancy test, and if they do not intend to become pregnant during the timeframe of the study. Women who are sexually active with a male partner must agree to use at least one of the following birth control methods: hormonal therapy such as oral, implantable or injectable chemical contraceptives; mechanical therapy such as spermicide in conjunction with a barrier such as a condom or diaphragm; intrauterine device (IUD); or surgical sterilization of partner. Women who are breast-feeding. Examination evidence of vitreoretinal interface disease (eg, vitreomacular traction, epiretinal membrane), either on clinical examination or OCT thought to be contributing to macular edema. An eye that, in the investigator's opinion, would not benefit from resolution of macular edema such as eyes with foveal atrophy, dense pigmentary changes or dense subfoveal hard exudates. Presence of an ocular condition that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (eg, age-related macular degeneration, uveitis or other ocular inflammatory disease, neovascular glaucoma, iris neovascularization, Irvine-Gass Syndrome, prior macula-off rhegmatogenous retinal detachment). Presence of a substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (ie, a 20/40 cataract). History of laser photocoagulation for macular edema within 3 months prior to randomization. History of intravitreal corticosteroid within 4 months of randomization. Intravitreal anti-VEGF injection within 2 months of randomization. Note: Enrollment will be limited to no more than 25% of the planned sample size with any history of anti-VEGF treatment. Once this number of eyes has been enrolled, any history of anti-VEGF treatment will be an exclusion criterion. For enrollment of study eyes with prior intravitreal anti-VEGF agents, in the opinion of the investigator, the treatment response to prior anti-VEGF treatment must be either incomplete or the study eye had developed recurrent CRVO-associated macular edema, such that the study eye would benefit from additional anti-VEGF treatment. History of peribulbar or retrobulbar corticosteroid use for any reason within 2 months prior to randomization. History of panretinal scatter photocoagulation (PRP) or sector laser photocoagulation within 3 months prior to randomization or anticipated within the next 3 months following randomization. History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within 4 months prior to randomization or anticipated within the next 6 months following randomization. History of yttrium aluminum garnet (YAG) capsulotomy performed within 2 months prior to randomization. Aphakia. Presence of an anterior chamber intraocular lens. Examination evidence of external ocular infection, including conjunctivitis, chalazion or significant blepharitis. History of macular detachment. Examination evidence of any diabetic retinopathy.
Information: https://secure.emmes.com/scoreweb
Study: Exploratory Study to Investigate the Bioactivity, Ocular and Systemic Safety, Tolerability, and Pharmacokinetics Following Single and Multiple Intravitreal Administrations of KSI-301 in Subjects With wAMD, DME and RVO
Clinicaltrials.gov Identifier: NCT03790852
Sponsor: Kodiak Sciences, Inc.
Purpose: This is a phase 1b open-label study to assess the bioactivity, ocular and systemic safety, tolerability, and pharmacokinetics of repeated injections of KSI-301 at 2 dose levels: 2.5 mg and 5 mg.
Design: Randomized, parallel assignment, no masking
Number of Patients: 50
Inclusion Criteria: RVO Cohort: Treatment naïve retinal vein occlusion with macular edema and secondary visual impairment. BCVA ETDRS letter score ≤78 and ≥23 (⁓20/25 to ⁓20/320 Snellen equivalent) in the study eye. Central subfield thickness (CST) of ≥300 microns on SD-OCT (Heidelberg Spectralis or equivalent). Branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) are both eligible. Decrease in vision in the study eye determined by the investigator to be primarily the result of macular edema secondary to RVO.
Exclusion Criteria: RVO Cohort: Initial diagnosis of RVO of more than 4 months from screening in the study eye. Active retinal or iris neovascularization in the study eye. Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant (dexamethasone or triamcinolone) in the study eye.
Information: jehrlich@kodiak.com, pablovm@kodiak.com
UVEITIS
Study: Systemic and Topical Antivirals for Control of Cytomegalovirus Anterior Uveitis: Treatment Outcomes (STACCATO)
Clinicaltrials.gov Identifier: NCT03586284
Sponsor: University of California, San Francisco
Purpose: A double-masked randomized controlled clinical trial comparing the efficacy of oral valganciclovir, topical ganciclovir 2%, and placebo for the treatment of PCR-proven CMV anterior uveitis. This pilot study will provide valuable information concerning the treatment of CMV anterior uveitis with oral and topical medications, including effective concentrations and side-effect profile. The information obtained from this study will help inform future larger clinical trials in CMV anterior uveitis.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 99
Inclusion Criteria: Clinical impression consistent with CMV anterior uveitis. Directed PCR positive for CMV OR previous PCR-proven CMV anterior uveitis. Willingness to use an acceptable method of contraception during the study period (i.e. pharmacologic, devices, barrier methods) or abstinence.
Exclusion Criteria: Patients <18 years of age. Intermediate or posterior inflammation (involvement of vitreous, choroid, or retina). Received antiviral therapy <14 days prior to enrollment. Received periocular or intraocular corticosteroid injection < 8 weeks prior to enrollment. Currently taking oral corticosteroids. Immunocompromised (primary or secondary immunosuppressive disorders). Prior immunosuppressive therapy in the past 6 months. Directed PCR negative for CMV. Directed PCR positive for herpes simplex virus (HSV) or varicella zoster virus (VZV). Planning to conceive during the study period, pregnant or breast-feeding (blood or urine pregnancy test for all females of child-bearing age is mandatory within 4 weeks prior to enrollment). Complete blood count with white blood cell, absolute neutrophil, or platelet count lower than the lower limit of reference laboratory normal. BUN or Cr above the upper limit of reference laboratory normal. Recent ocular surgery within the past 30 days, or planned surgery within the next 45 days. Systemic autoimmune disease or ocular condition (besides anterior uveitis) anticipated to dictate or alter treatment course.
Information: john.gonzales@ucsf.edu
Study: A 48 Week Study to Evaluate the Efficacy and Safety of Two (2) EYS606 Treatment Regimens in Subjects With Active Chronic Non-infectious Uveitis (CNIU) (ELECTRO)
Clinicaltrials.gov Identifier: NCT04207983
Sponsor: Eyevensys
Purpose: The objective of the study is to evaluate the efficacy and safety of two different treatment regimens of EYS606.
Design: Randomized, parallel assignment
Number of Patients: 56
Inclusion Criteria: Subject must be 18 years of age or older. Subject must have a diagnosis of chronic non-infectious uveitis of any anatomic subtype (anterior, intermediate, posterior or panuveitis). Subject must have a history of chronic or recurrent non-infectious uveitis requiring or having required treatment with corticosteroids (systemic, periocular or intraocular) and/or systemic immunosuppressive medication(s) in the 12 months prior to the screening visit. Best corrected visual acuity of Study Part I: ≥5 and <67 ETDRS letters in the study eye (equivalent to less than or equal to 20/50 but better than or equal to 20/800 Snellen). Study Part II: ≥5 and <77 ETDRS letters in the study eye (equivalent to less than or equal to 20/32 but better than or equal to 20/800 Snellen). At the screening and baseline visits subject must have active chronic non-infectious uveitis as evidenced by at least one or more of the following in the study eye: Active retinal vasculitis (retinal vascular leakage) involving the posterior pole confirmed by the reading center. Vitreous haze grade ≥2+ (SUN classification). Anterior chamber cell grade ≥2+ (SUN classification); anterior chamber cells must be present for subjects with a diagnosis of chronic anterior non-infectious uveitis. Persistent macular edema (defined as central retinal thickness (CRT) >300 microns or >320 microns using Zeiss Cirrus and Topcon or Heidelberg Spectralis spectral domain ocular coherence tomography (SD-OCT) instruments, respectively) despite treatment with corticosteroids and/or immunosuppressive therapy for at least 4 weeks prior to screening. Subject receiving concomitant topical and/or systemic corticosteroids or allowed systemic immunosuppressive medications must have maintained the same treatment regimen (dosage/frequency) for at least 2 weeks prior to the baseline (V1) visit, (if applicable).
Information: ronald.buggage@eyevensys.com
Study: Efficacy and Safety of H.P. ACTHAR GEL in Adults with Retinal Vasculitis
Clinicaltrials.gov Identifier: NCT03066869
Sponsor: Ocular Immunology and Uveitis Foundation
Purpose: The purpose of this study is to evaluate the short- and long-term efficacy and safety of Acthar for the treatment of adults with non-infectious retinal vasculitis.
Design: Single group, no masking
Number of Patients: 40
Inclusion Criteria: Any adult patient with active retinal vasculitis (involving arteries or veins) as a manifestation of non-infectious ocular inflammatory disease; fundus must be viewable with wide-field FA in the study eye. If both eyes are involved, both are eligible for inclusion in the study. Patients already on nonsteroidal immunosuppressive therapy may continue on this during the study, but the dose must not be increased or decreased within 6 weeks of initiating the trial. Willing and able to sign the informed consent form.
Exclusion Criteria: Patients under age 18. Patients who are pregnant (must be ruled out in women of child-bearing age). Active infectious ocular or systemic disease. Patients with active infectious ocular or extraocular disease. Patients with history of malignancy, except for dermatologic entities of basal or squamous cell carcinoma which have been completely excised or removed previously. Patients with systemic illness involving abnormalities of the hypothalamic-pituitary-adrenal axis; patients with primary adrenocortical insufficiency or adrenocortical hyperfunction. Patients with known hypersensitivity to Acthar. Patients on other non-steroidal systemic immunomodulatory medications with dose adjusted sooner than 6 weeks prior to study drug administration. Patients currently on or recently treated with (within 6 weeks) systemic corticosteroid. Patients with periocular or intraocular injections of medications administered to help control inflammation sooner than 6 weeks prior to study drug administration. Patients with severe disease that warrants critical attention, deemed unsafe for the study by the investigator, or contraindicated, including but not limited to, patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, or sensitivity to proteins of porcine origin. Administration of live or live attenuated vaccines is contraindicated in patients during the entire duration of the study and for 1 month prior.
Information: sfoster@mersi.com
Study: Assessment of the Anti-inflammatory Effects of Norflo Oro in Acute Relapses of HLA-B27 Associated Autoimmune Uveitis
Clinicaltrials.gov Identifier: NCT03584724
Sponsor: Eye Pharma; Bascom Palmer Eye Institute
Purpose: The purpose of this study is to explore the efficacy of Norflo Oro in the treatment of relapsing autoimmune uveitis (RAU), measured as a long term reduction of the frequency and the severity of relapses, in patients with HLA-B27 associated uveitis, under conditions of routine medical practice. The reduction of the mean number of relapses per patient between the year before study treatment and the study period will also be assessed.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 5
Inclusion Criteria: Clinical diagnosis of HLA-B27 positive related uveitis in nonacute phase. At least 1 autoimmune uveitis relapse.
Exclusion Criteria: Use of supplements (nutraceuticals) or systemic therapy for uveitis with anti-inflammatory immunosuppressive or biological drugs within last 30 days. Anticipated need for systemic anti-inflammatory treatment during the study. Use of intravitreal peribulbar, sub-tenon, periocular injection in the previous 6 months. Long-term treatment with a systemic anti-inflammatory, immune suppressant drugs. Woman taking hormonal contraceptives, pregnant or breastfeeding.
Information: laceyfeigl@wustl.edu
Study: Tofacitinib for Inflammatory Eye Disease
Clinicaltrials.gov Identifier: NCT03580343
Sponsor: Washington University School of Medicine
Purpose: Non-infectious inflammatory eye disease, such as uveitis and scleritis, is a chronic, autoimmune process that leads to vision loss. While steroids are effective in the short term, the side-effect profile of chronic steroid use necessitates the identification of effective steroid-sparing therapies. Tofacitinib is a small molecule that inhibits the signaling pathways of multiple inflammatory cytokines. The investigators plan to evaluate whether tofacitinib may have efficacy for patients with uveitis and/or scleritis.
Design: Single group, no masking
Number of Patients: 5
Inclusion Criteria: Diagnosis of uveitis; a clinical response to steroids; active disease requiring at least 10mg of prednisone daily (or steroid equivalent).
Exclusion Criteria: Suspected or confirmed ocular infection; chronic or recurring infections, such as HIV; renal insufficiency that would preclude safe administration of tofacitinib.
Information: laceyfeigl@wustl.edu
Study: Adalimumab vs Conventional Immunosuppression for Uveitis Trial (ADVISE)
Clinicaltrials.gov Identifier: NCT03828019
Sponsor: JHSPH Center for Clinical Trials
Purpose: Based upon preliminary data, adalimumab, a fully-human, anti-TNF-α monoclonal antibody, now US FDA-approved for uveitis treatment, may be a superior corticosteroid-sparing agent than conventional immunosuppressive drugs. The ADVISE Trial is multicenter randomized, parallel-treatment, comparative effectiveness trial comparing adalimumab to conventional (small molecule) immunosuppression for corticosteroid spring in the treatment of non-infectious, intermediate, posterior, and panuveitides.
Design: Randomized, parallel assignment, no masking
Number of Patients: 222
Inclusion Criteria: Age 13 years or older; active or recently active (≤60 days) non-infectious, intermediate, posterior, or panuveitis; prednisone indication meets one of the following: a. Active uveitis requiring one of the following i. Initiation of prednisone at dose greater than 7.5 mg/day ii. Increasing prednisone dose to greater than 7.5 mg/day iii. Currently receiving dose greater than 7.5 mg/day; b. Inactive uveitis on current dose greater 7.5 mg/day. Initiation or addition of an immunosuppressive drug (ie, a conventional immunosuppressive drug or adalimumab) is indicated. If currently receiving a conventional immunosuppressive drug, the drug and dose have been stable for at least 30 days. Patient able and willing to self-administer subcutaneous injections or have a qualified person available to administer subcutaneous injections. If posterior segment disease is present, ability to assess activity in at least 1 eye with uveitis. Visual acuity of light perception or better in at least 1 eye with uveitis.
Exclusion Criteria: Active tuberculosis or untreated latent tuberculosis (eg, positive interferon-γ release assay [IGRA] test, such as Quantiferon-gold). Untreated active hepatitis B or C infection. Behçet disease. Multiple sclerosis. For patients with intermediate uveitis, abnormal magnetic resonance imaging (MRI) of the brain consistent with demyelinating disease. Use of anti-TNF monoclonal antibody therapy within past 60 days. History of adalimumab intolerance or ineffectiveness. Current treatment with an alkylating agent. Current treatment with more than 1 immunosuppressive drug, not including oral corticosteroids. Shorter-acting regional corticosteroids administered within the past 30 days in any eye(s) with uveitis. Long-acting ocular corticosteroid implants, ie, fluocinolone acetonide implant (eg, Retisert, Yutiq, Iluvien) placed within past 3 years unless uveitis is active in all eye(s) with an implant. Systemic disease that is sufficiently active such that it dictates therapy with systemic corticosteroids or immunosuppressive agents at the time of enrollment. Immunodeficiency disease for which immunosuppressive therapy would be contraindicated according to best medical judgment. Pregnancy, lactation, or for women of child-bearing potential unwillingness to use appropriate birth control for the duration of the trial. Medical problems or drug or alcohol dependence problems sufficient to prevent adherence to treatment and study procedures.
Information: jholbro1@jhu.edu, esugar2@jhu.edu
Study: OCT Technology Development to Assess Ocular Integrity and Characterize Ocular Integrity and Intraocular Scatterers
Clinicaltrials.gov Identifier: NCT03531853
Sponsor: Duke University
Purpose: The purpose of this study is to develop and demonstrate new technologies that will enable a non-contact, compact eye imaging system based on OCT to assist an early responder in acute care settings (like an emergency room) to help assess eye trauma and inflammation (swelling inside the eye).
Design: Single group, open label
Number of Patients: 75
Inclusion Criteria: Pre-clinical: employees or students (over the age of 18) of the Duke Eye Center or Biomedical Engineering willing to be imaged with OCT system; pilot (ER): patients (over the age of 18) presenting emergently to the Duke Emergency room with traumatic eye injuries and/or suspected open globe; pilot uveitis): patients presenting to the Duke Eye Center with active uveitis and microhyphema or hyphema; patients who have independently consented to undergo vitreous tap or biopsy for their uveitis care at the Duke Eye Center.
Exclusion Criteria: Preclinical: subject cannot be a direct report to any of the PIs or other key personnel of this study; pilot (ER): hemodynamically unstable, unable to consent; pilot (Uveitis): unable to consent; cornea or lens opacity/scar which would block the imaging modality.
Information: teresa.hawks@duke.edu
Study: A Phase III Study Assessing the Efficacy and Safety of Intravitreal Injections of 440 ug DE-109 for the Treatment of Active, Non-Infectious Uveitis of the Posterior Segment of the Eye (LUMINA)
Clinicaltrials.gov Identifier: NCT03711929
Sponsor: Santen Inc.
Purpose: This is a phase III study to assess the efficacy and safety of DE-109 440 µg every 2 months in subjects with active, non-infectious uveitis of the posterior segment of the eye (NIU-PS).
Design: Randomized, parallel assignment, quadruple-blind, treatment
Number of Patients: 200
Inclusion Criteria: Noninfectious active uveitis of the posterior segment.
Exclusion Criteria: Females who are pregnant, nursing, or planning a pregnancy; confirmed or suspected infectious uveitis.
Information: clinicaltrials@santen.com
Study: ACTH as A Re-emerging theRapy for Uveitis (The ACTHAR Study) (ACTHAR)
Clinicaltrials.gov Identifier: NCT02931175
Sponsor: Quan Dong Nguyen
Purpose: The study aims to evaluate the potential role of ACTH gel in the management of non-infectious uveitis.
Design: Randomized, parallel assignment, no masking
Number of Patients: 36
Inclusion Criteria: In order to be eligible for the study, patients will be required to meet the criteria of 1 of the 3 following disease cohorts: Active disease and are receiving no treatment. Active disease is defined as having at least 1+ Vitreous Haze using the Standardized Uveitis Nomenclature (SUN) Working Group scale and/or at least 1+ Vitreous Cell Count using Foster & Vitale scale. Active disease and are receiving prednisone ≥10 mg/day (or equivalent dose of another corticosteroid) or at least 1 other systemic immunosuppressant (all systemic immunosuppressants other than corticosteroids will be discontinued 30 days prior to the first administration of the study drug on day 0). Patients receiving combination of prednisone ≥10 mg/day and at least 1 other systemic immunosuppressant are also eligible in this category. Have inactive disease, defined as having <= 0.5+ Vitreous Haze OR <= 0.5+ Vitreous Cell Count (SUN scale), and are receiving prednisone ≥10 mg/day (or equivalent dose of another corticosteroid) or at least 1 other systemic immunosuppressant (all systemic immunosuppressants other than corticosteroids will be discontinued 30 days prior to the first administration of the study drug on day 0). Patients receiving combination of prednisone ≥10 mg/day and at least 1 other systemic immunosuppressant are also eligible in this category.
Exclusion Criteria: Subjects who have any of the following at the screening visit are not eligible for enrolment in this Study: Any significant ocular disease that could compromise vision in the study eye. These include, but are not limited to: Diabetic retinopathy: proliferative diabetic retinopathy (PDR) or non-proliferative diabetic retinopathy (NPDR) that compromise the vision. Age-related macular degeneration; Myopic degeneration with active subfoveal choroidal neovascularization. Advanced glaucoma status post trabeculectomy or tube/valve placement. Any of the following treatments within 90 days prior to day 0 or anticipated use of any of the following treatments to the study eye: Intravitreal injections (including but not limited to steroids or anti-vascular endothelial growth factors); Posterior subtenon's steroids. Intraocular surgery within 90 days prior to day 0 in the study eye; Capsulotomy within 30 days prior to day 0 in the study eye; Any known ocular surgery (including cataract extraction or capsulotomy) of the study eye anticipated within the first 180 days following day 0; Intraocular pressure(IOP) ≥25 mmHg in the study eye (glaucoma patients maintained on no more than 2 topical medications with IOP <25 mmHg are allowed to participate); Pupillary dilation inadequate for quality stereoscopic fundus photography in the study eye; Media opacity that would limit clinical visualization; Presence of any form of ocular malignancy in the study eye, including choroidal melanoma; History of herpetic infection in the study eye or adnexa; Presence of known active or inactive toxoplasmosis in either eye; Presence of ocular or periocular infection in either eye; Participation in other investigational drug or device clinical trials within 30 days prior to day 0, or planning to participate in other investigational drug or device clinical trials within 180 days following day 0. This includes both ocular and non-ocular clinical trials. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization. Prior treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are anti-cluster of differentiation (CD) 4, anti-cluster of differentiation (CD)5, anti-cluster of differentiation (CD) 3, anti-cluster of differentiation (CD)19 and anti-cluster of differentiation (CD)20. Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline. Immunization with a live/attenuated vaccine within 4 weeks prior to baseline. Previous treatment with ACTHAR within 3 months of day 0 of study visit. Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
Information: imaging@oirrc.net
Study: Humboldt: Efficacy and Safety of Filgotinib in Adults with Active Noninfectious Uveitis
Clinicaltrials.gov Identifier: NCT03207815
Sponsor: Gilead Sciences
Purpose: The primary objective of this study is to evaluate the efficacy of filgotinib vs placebo for the treatment of the signs and symptoms of noninfectious uveitis in participants failing treatment for active noninfectious uveitis.
Design: Randomized, parallel assignment, double masking, treatment
Number of Patients: 110
Inclusion Criteria: Is diagnosed with noninfectious intermediate-, posterior-, or panuveitis; Must have active uveitic disease at the day 1/baseline visit as defined by the presence of at least 1 of the following parameters in at least 1 eye despite 2 weeks or more of maintenance therapy with oral prednisone (≥10 mg/day to ≤60 mg/day) or oral corticosteroid equivalent: Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion; ≥2+ anterior chamber cells per the Standardization of Uveitis Nomenclature (SUN) criteria; ≥2+ vitreous haze per the National Eye Institute/Standardization of Uveitis Nomenclature (NEI/SUN) criteria. No evidence of active tuberculosis (TB), history of prior TB or latent TB meeting the screening criteria.
Exclusion Criteria: Adults with severe glaucoma at screening are not eligible to participate; severe glaucoma is defined as: Intraocular pressure of ≥25 mmHg and on ≥2 glaucoma medications and/or; Any evidence of glaucomatous optic nerve injury. Confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, cytomegalovirus (CMV), Human T-Lymphotropic Virus Type 1 (HTLV-1), Whipple's disease, Herpes Zoster virus (HZV), Lyme disease, toxoplasmosis and herpes simplex virus (HSV). Adults with a prior failure of anti-tumor necrosis factor (TNF) therapy or previous exposure to any biologic therapy (except intravitreal anti-vascular endothelial growth factor [VEGF] therapy) with a potential therapeutic impact on noninfectious uveitis within 90 days of day 1/ baseline are not eligible to participate.
Information: Gileadclinicaltrials@gilead.com
Study: MERIT: Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial
Clinicaltrials.gov Identifier: NCT02623426
Sponsor: JHSPH Center for Clinical Trials
Purpose: This trial will compare the relative efficacy and safety of intravitreal methotrexate, intravitreal ranibizumab, and the intravitreal dexamethasone implant for the treatment of uveitic macular edema persisting or reoccurring after an intravitreal corticosteroid injection. MERIT is a parallel design (1:1:1), randomized comparative trial with an anniversary close-out at the 6-month clinic visit. The primary outcome is percent change in central subfield thickness from the baseline OCT measurement to the 12 week visit.
Design: Randomized, parallel assignment, single masking, treatment
Number of Patients: 240
Inclusion Criteria: 18 years of age or older; at least 1 eye must meet all of the following conditions; Inactive or minimally active noninfectious anterior, intermediate, posterior or panuveitis, as defined by SUN132 criteria as ≤0.5+ anterior chamber cells, ≤0.5+ vitreous haze grade and no active retinal/choroidal lesions for a minimum of 4 weeks; Macular edema (ME) defined as the presence of macular thickness greater than the normal range for the OCT machine being used (see cut points below), regardless of the presence of cysts, following an intravitreal corticosteroid injection (≥4 weeks following intravitreal triamcinolone injection or ≥12 weeks following intravitreal dexamethasone implant injection); Greater than 300 μm for Zeiss Cirrus Greater than 320 μm for Heidelberg Spectralis Greater than 300 μm for Topcon 3DOCT; baseline fluorescein angiogram that, as assessed by the study ophthalmologist, is gradable for degree of leakage in the central subfield; Best corrected visual acuity (BCVA) 5/200 or better; baseline intraocular pressure >5 mm Hg and ≤21 mm Hg (current use of ≤3 intraocular pressure-lowering medications and/or prior glaucoma surgery are acceptable (Note: combination medications, eg, Combigan, are counted as 2 IOP-lowering medications); Media clarity and pupillary dilation sufficient to allow OCT testing and assessment of the fundus.
Exclusion Criteria: History of infectious uveitis in either eye; History of infectious scleritis of any type in either eye (Note: History of noninfectious scleritis that has been active in past 12 months is an eye-level exclusion -see #13 below); History of keratitis (with the exception of keratitis due to dry eye) in either eye; History of central serous retinopathy in either eye; Active infectious conjunctivitis in either eye; Oral prednisone dose >10 mg per day (or of an alternative corticosteroid at a dose higher than that equipotent to prednisone 10 mg per day) OR oral prednisone dose ≤10 mg per day at baseline that has not been stable for at least 4 weeks (note: if patient is off of oral prednisone at baseline (M01 study visit) dose stability requirement for past 4 weeks does not apply); Systemic immunosuppressive drug therapy that has not been stable for at least 4 weeks (note: use of systemic methotrexate is acceptable as long as regimen has been stable for at least 4 weeks); Use of oral acetazolamide or other systemic carbonic anhydrase inhibitor at baseline; Known allergy or hypersensitivity to any component of the study drugs; For women of childbearing potential: pregnancy, breastfeeding, or a positive pregnancy test; unwilling to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for duration of trial; Eye level exclusion criteria - at least 1 eye that meets all inclusion criteria cannot have any of the following conditions: History of infectious endophthalmitis; History of severe glaucoma as defined by optic nerve damage (cup/disc ratio of ≥0.9 or any notching of optic nerve to the rim); History of active noninfectious scleritis in past 12 months (Note: History of noninfectious scleritis is acceptable if the last episode of active scleritis resolved at least 12 months prior to enrollment); Presence of an epiretinal membrane noted clinically or by OCT that per the judgment of study ophthalmologist may be significant enough to limit improvement of ME (ie, causing substantial wrinkling of the retinal surface); Torn or ruptured posterior lens capsule; Presence of silicone oil; Ozurdex administered in past 12 weeks; Anti-VEGF agent, intravitreal methotrexate, or intravitreal/periocular corticosteroid administered in past 4 weeks; Fluocinolone acetonide implant (Retisert) placed in past 3 years.
Information: jholbro1@jhu.edu, esugar2@jhu.edu
Study: SAVE-2: Intravitreal Sirolimus as Therapeutic Approach to Uveitis
Clinicaltrials.gov Identifier: NCT01280669
Sponsor: Stanford University, Santen Inc.
Purpose: The purpose of this study is to find out about the safety and effectiveness of 2 different doses the study drug, sirolimus, administered intravitreally in patients with uveitis.
Design: Randomized, parallel assignment, no masking
Number of Patients: 30
Inclusion Criteria: >12 years of age, able to give consent, have diagnosis of uveitis, have active uveitis, defined as having at least 1+ Vitreous Haze and/or at least 1+ Vitreous Cell Count (SUN scale), and: are receiving no treatment; or are receiving: prednisone ≥10 mg/day (or equivalent dose of another corticosteroid), or at least 1 systemic immunosuppressant other than corticosteroids, or combination of prednisone ≥10 mg/day (or equivalent dose of another corticosteroid) and other systemic immunosuppressant. Have inactive disease, defined as having 0.5+ vitreous haze or less and 0.5+ or less vitreous cell count (SUN scale), and are receiving: prednisone <10 mg/day (or equivalent dose of another corticosteroid), or at least 1 systemic immunosuppressant other than corticosteroids, or combination of prednisone <10 mg/day (or equivalent dose of another corticosteroid) and other systemic immunosuppressant. Have posterior, intermediate, or panuveitis; for panuveitis, if an anterior component is present, it must be less than the posterior component. Sufficient inflammation to require systemic treatment and, based on the Investigator's decision, warrants intravitreal treatment. Best-corrected ETDRS visual acuity of 20/400 or better (approximately 20 letters) in the study eye. Best-corrected ETDRS visual acuity of 20/400 or better in the fellow eye (approximately 20 letters).
Exclusion Criteria: Patients with bilateral uveitis who are receiving systemic immunosuppressive therapy (eg, methotrexate, cyclosporine, cyclophosphamide, chlorambucil, mycophenolate mofetil, tacrolimus, or azathioprine) other than prednisone or other corticosteroids for the treatment of uveitis and the uveitis in the fellow eye, in the opinion of the Investigator, cannot be controlled with standard local therapies alone; Any significant ocular disease that could compromise the visual outcome in the study eye. Intravitreal injections (including but not limited to anti-vascular endothelial growth factors 60 days prior to the baseline; Posterior subtenon's or intravitreal injection of steroids 90 days prior to baseline; Intraocular surgery within 90 days prior to day 0 in the study eye; Capsulotomy within 30 days prior to day 0 in the study eye; History of vitreoretinal surgery or scleral buckling within 90 days prior to day 0 in the study eye; Any ocular surgery (including cataract extraction or capsulotomy) of the study eye anticipated within the first 180 days following day 0; Intraocular pressure ≥25 mmHg in the study eye (glaucoma patients maintained on no more than 2 topical medications with IOP <25 mmHg are allowed to participate); Pupillary dilation inadequate for quality fundus photography in the study eye; Media opacity that would limit clinical visualization, intravenous fluorescein angiography (IVFA), or OCT evaluation in the study eye; Presence of any form of ocular malignancy in the study eye, including choroidal melanoma; History of herpetic infection in the study eye or adnexa; Presence of known active or inactive toxoplasmosis in either eye; Ocular or periocular infection in either eye; Participation in other investigational drug or device clinical trials within 30 days prior to day 0, or planning to participate in other investigational drug or device clinical trials within 180 days following day 0. This includes both ocular and nonocular clinical trials.
Information: ndquan@stanford.edu, lgreer7@stanford.edu
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