DRY AMD

NEW: QA102 Phase II Study in Subjects With Dry AMD (AMEND)

Clinicaltrials.gov Identifier: NCT05536752

Sponsor: Smilebiotek Zhuhai Limited

Purpose: This is a phase 2, double-masked, randomized, placebo-controlled, dose-response study. The primary objective of the study is to evaluate the efficacy of QA102 oral capsules on the development of GA or CNV in high-risk eyes.

Design: Randomized, parallel assignment, triple masking

Number of Patients: 240

Inclusion Criteria: Subject must be able to understand and willing to sign a written informed consent form (ICF) prior to the initiation of any study-specific procedures. Subject must be age ≥50 years at the time of informed consent. Subject must be able to take oral medications and willing to record daily adherence to taking their assigned capsules. Subject must have adequate hematologic function, hepatic function, renal function and coagulation profile as defined in the protocol. Subject must be willing and able to comply with study procedures and examinations. Specific to the study eye: Subject must have one of the following: extensive intermediate-size drusen, or at least 1 large drusen, or at least one GA secondary to AMD, with very limited aggregate size of total GA(s), as defined in the protocol. Subject must be able to correctly identify ≥35 ETDRS letters (approximately 20/200 Snellen equivalent). Specific to Fellow Eye: Subject must have had a diagnosis of advanced AMD (GA or CNV) within the 12 months prior to screening. Specific to both eyes: Subject must have visualizable retina, clear ocular media, and adequate pupillary dilation to ensure high-quality fundus imaging.

Exclusion Criteria: Subject participated in another clinical study within 6 weeks prior to Screening. Subject is unwilling to stop intake of Age-Related Eye Disease Studies (AREDS) vitamins for the duration of the study. Subject has a clinically significant systemic disease that might interfere with the study, in the judgment of the Investigator. Subject had major surgery within 30 days prior to Screening. Specific to Study Eye: Subject has large GA, subfoveal GA, or active or inactive CNV, as confirmed by the CRC. Subject has GA or CNV due to causes other than AMD that developed between visit 1 (screening) and visit 2 (randomization). Subject has endophthalmitis. Specific to either eye: Subject had intraocular surgery with lens replacement within 3 months of screening. Subject has any ophthalmic condition that could require surgery during the study period. Subject has an ocular condition that might affect adequate imaging of the retina and/or or alter visual acuity.

Information: jason.herter@ming-med.com

Study: A Study of Danicopan in Participants With Geographic Atrophy Secondary to Age-related Macular Degeneration

Clinicaltrials.gov Identifier: NCT05019521

Sponsor: Alexion Pharmaceuticals

Purpose: This is a dose-finding study designed to evaluate the efficacy, safety, and pharmacokinetics of danicopan in participants with GA secondary to AMD. The study consists of a screening Period of up to 4 weeks, a 104-week masked Treatment Period, followed by an Open-label Extension (OLE) Period starting at Week 104 and lasting for up to 1 year. This study will have 4 treatments arms: 100 milligrams (mg) twice daily (bid), 200 mg bid, 400 mg once daily (qd), and matching placebo.

Design: Randomized, parallel assignment, quadruple masked

Number of Patients: 330

Inclusion Criteria: Documentation of vaccination for Neisseria meningitidis. Capable of giving signed informed consent. Presentation of GA secondary to AMD in at least 1 eye with new inclusion criterion. The entire GA lesion must be extrafoveal without foveal involvement.

Exclusion Criteria: GA in either eye due to cause other than AMD. Have previously received intravitreal anti-VEGF injections in study eye. Have previously received any complement/stem cell/gene therapy for any ophthalmological condition. Previous participation in interventional clinical studies for treatment of drusen, nascent GA, or GA (except vitamins or minerals) irrespective of route of administration (ocular or systemic) in either eye. Presence of active ocular diseases in either eye that in the opinion of the investigator compromises or confounds visual function or interferes with study assessments. Known or suspected complement deficiency. History or presence of any clinically relevant comorbidities or any uncontrolled conditions. Hypersensitivity to fluorescein sodium for injection, the investigational drug (danicopan), or any of its excipients.

Information: clinicaltrials@alexion.com

Study: A Masked, Placebo-controlled Study to Assess Iptacopan in Age-related Macular Degeneration

Clinicaltrials.gov Identifier: NCT05230537

Sponsor: Novartis Pharmaceuticals

Purpose: The purpose of this study is to assess the effect of Iptacopan (LNP023) to prevent conversion of early or intermediate age-related macular degeneration (AMD) eyes to new incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) or late AMD.

Design: Randomized, parallel assignment, triple masked

Number of Patients: 146

Inclusion Criteria: Male or female participants ≥50 years of age. Diagnosis of early or intermediate age-related macular degeneration (AMD) in the study eye as determined by the investigator on fundus examination. Study eye (early/intermediate AMD eye) must have at least one high risk optical coherence tomography (OCT) feature (as defined by a central reading center). Diagnosis of neovascular AMD (nAMD) in the fellow eye as determined by the investigator. Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection are required prior to the start of the treatment with LNP023. If not received previously, vaccination against Haemophilius influenzae infection should be given, if available and according to local regulations.

Exclusion Criteria: Concomitant medical or ocular conditions which could compromise visual acuity, require planned medical or surgical intervention during the study period, preclude scheduled study visits, completion of the study, or safe administration of the investigational product, including intraocular surgery, cataract and vitreoretinal surgery in the study eye within 3 months prior to Baseline/day 1 and the presence of significant media opacity, eye movement disorder (nystagmus), severe ptosis, extraocular motility restriction or head tremor. History of clinically significant electrocardiogram (ECG) abnormalities, or any of the following ECG abnormalities at screening or baseline/day 1 visit: QT interval corrected by Fridericia's formula (QTcF) >450 msec (males). QTcF >460 msec (females). History of familial long QT syndrome or known family history of Torsades de Pointes. History of stroke or myocardial infarction during the 6-month period prior to Baseline/day 1, any current clinically significant arrhythmias, or any advanced cardiac or severe pulmonary hypertension. History of kidney failure including end-stage renal disease requiring dialysis or renal transplant. History of malignancy of any organ system. History of solid organ or bone marrow transplantation. History of recurrent meningitis or history of meningococcal infections despite vaccination. History of immunodeficiency diseases, including a positive Human Immunodeficiency Virus test result at screening. Chronic infection with Hepatitis B or Hepatitis C. History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes or clinically relevant sensitivity to fluorescein dye as assessed by the investigator.

Information: novartis.email@novartis.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, or pseudovitelliform maculopathy.

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 color fundus photography (CFP). GA lesions total size in the study eye must be ≥1.25 mm² and ≤17.5 mm² 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 2 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 D of myopia) or history of significant amblyopia (either eye). Any other significant ocular or nonocular 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 2 forms of contraception (one of which being a barrier method) 90 days for men and 30 days for women postdosing, 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 2 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 2 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 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, uncontrolled IOP, use of 2 or more topical agents to control IOP, or a history of glaucoma filtering surgery in the study eye. Axial myopia of greater than –8 D 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 2 forms of contraception (one of which being a barrier method) for 90 days postdosing, if relevant. Have a history or presence of cutaneous squamous cell carcinoma. 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.

Information: clinicaltrials@gyroscopetx.com

Study: EXPLORE: A Phase 2 Study to Evaluate the Safety and Efficacy of 2 Doses of GT005

Clinicaltrials.gov Identifier: NCT04437368

Sponsor: Gyroscope Therapeutics

Purpose: The purpose of this clinical study is to evaluate the safety and efficacy of 2 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 2 or more topical agents to control IOP, or a history of glaucoma filtering surgery. Axial myopia of greater than -8.0 D 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 2 forms of contraception (one of which being a barrier method) for 90 days postdosing, 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 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, 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 5 years after treatment. Clinical findings consistent with advanced dry AMD with evidence of one or more areas of ≥1.25 mm² 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 -8.0 D 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 D 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 (eg, 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 (eg, 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 (ie, 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 (eg, 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, subretinal 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: 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 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). (Note: 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 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 nonmelanoma skin or squamous cell cancer or cervical carcinoma in situ. Is nonambulatory. 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: 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 mm² 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 -8.0 D 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: 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 to 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: Evaluation of OLX10212 in Patients With Neovascular Age-related Macular Degeneration

Clinicaltrials.gov Identifier: NCT05643118

Sponsor: Olix Pharmaceuticals, Inc.

Purpose: This is a phase 1, multicenter, open-label, single- and multi-dose, dose-escalating study of OLX10212 in patients with neovascular age-related macular degeneration (AMD). This study is composed of 2 parts: part A and part B. Part A is a single ascending dose study, and part B is a multiple ascending dose study. The primary objective is to evaluate the safety and tolerability of single and multiple intravitreal injection(s) of OLX10212 in patients with neovascular AMD. The exploratory objectives are to evaluate the preliminary efficacy of single and multiple intravitreal injection(s) of OLX10212 in patients with neovascular AMD, and to evaluate the pharmacokinetics (PK) of single and multiple intravitreal injection(s) of OLX10212 in patients with neovascular AMD.

Design: Nonrandomized, sequential assignment, no masking

Number of Patients: 60

Inclusion Criteria: Men and women ≥50 years of age. Primary subfoveal CNV lesions secondary to AMD, including juxtafoveal lesions that affect the fovea, as evidenced by FA in the study eye. CNV must be ≥50% of the total lesion size in the study eye. ETDRS BCVA score ranging from 20/80 to 20/400 in the study eye. Clear ocular media and adequate pupillary dilation (able to dilate pupil to ≥4 mm using standard mydriatics) in the study eye to permit good stereoscopic fundus photography. Retinal thickness ≥250 μm in the macular region of the study eye as measured by SD-OCT with the presence of intraretinal or subretinal fluid. 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 by a family member), understand, and willing to sign the informed consent form.

Exclusion Criteria: Any prior systemic treatment for neovascular AMD in either eye, except dietary supplements or vitamins or systemic anti-VEGF therapy, or planned use at any time during the study. Any prior treatment in the study eye with another investigational agent to treat neovascular AMD within 6 months prior to day 0 or planned use at any time during the study. Prior treatment with anti-VEGF agents as follows: Anti-VEGF therapy in the study eye within 4 weeks prior to day 0. Anti-VEGF therapy in the study eye at any time to which there was no response, as defined by the presence of at least 1 of the following conditions: (1) persistent (plasma) fluid exudation, (2) unresolved or new hemorrhage, and (3) progressive lesion fibrosis. Anti-VEGF therapy in the fellow eye with an investigational agent (not FDA approved, unless it is bevacizumab) within 3 months prior to day 0 (prior treatment with an FDA approved anti-VEGF therapy in the fellow eye is allowed at any time). Systemic anti-VEGF therapy, investigational or FDA approved, within 3 months prior to day 0 or planned use at any time during the study. Subretinal hemorrhage in the study eye that is either >50% of the total lesion size or, if the blood is under the fovea, ≥1 disc area in size. Scar or fibrosis in the study eye involving >50% of the total lesion size. Retinal pigment epithelial tears or rips in the study eye involving the macula. History of any vitreous hemorrhage in the study eye within 4 weeks prior to day 0. Presence of other causes of CNV in the study eye, including pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis. History or clinical evidence of diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina (other than AMD) in either eye. History of stage ≥2 macular hole in the study eye. Any prior intraocular or periocular surgery on the study eye within 3 months prior to day 0 (lid surgery is allowed if it took place at least 1 month prior to Day 0 and is unlikely to interfere with OLX10212 injection). Prior vitrectomy in the study eye, surgery for retinal detachment in the study eye, and prior trabeculectomy or other filtration surgery in the study eye are not permitted at any time. Uncontrolled glaucoma (defined as IOP ≥25 mmHg despite treatment with antiglaucoma medication) in the study eye. Glaucoma in the study eye requiring treatment with 3 or more antiglaucoma medications. Active intraocular inflammation or history of uveitis in either eye. Presence or history of ocular or periocular infection in either eye within 2 weeks prior to day 0. Presence or history of scleromalacia in either eye. Aphakia or absence of posterior capsule in the study eye (unless due to yttrium aluminum garnet [YAG] posterior capsulotomy). Prior therapeutic radiation in the region of the study eye or planned use at any time during the study. Prior corneal transplant in the study eye. Significant media opacities, including cataract, in the study eye that, in the opinion of the Investigator, could 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 (1) require either medical or surgical intervention during the 24- or 32-week study period (part a or part B, respectively), (2) increase the risk to the patient beyond what is to be expected from standard intraocular injection procedures, or (3) otherwise interfere with the injection procedure or efficacy or safety evaluation. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications. Participation as a patient in any clinical study or prior systemic or ocular treatment with an investigational agent within 12 weeks prior to day 0. Prior systemic or intraocular treatment with long-acting steroids within 6 months prior to Day 0 or planned use at any time during the study. History of allergy to povidone iodine. Known allergy to fluorescein sodium for injection in angiography. Unwillingness among females who are pregnant, breastfeeding, or of childbearing potential to practice adequate contraception throughout the study. Adequate contraceptive measures include oral contraceptives (stable use for ≥2 cycles prior to day 0), intrauterine device, Depo-Provera (Pfizer, Inc., New York) or Norplant System (Pfizer, Inc., New York) implants, bilateral tubal ligation, vasectomy, and condom or diaphragm plus contraceptive sponge, foam, or jelly. A female is considered to be of childbearing potential unless she is premenstrual, 1 year postmenopausal, or 3 months post-surgical sterilization. All females of childbearing potential, including those with post-tubal ligation, must have a negative urine pregnancy test result at Day 0 and every 4 weeks as outlined in the Schedule of Activities. A negative serum pregnancy test must be obtained at Screening.

Information: yikim@olixpharma.com

NEW: 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: This is a study in people with an eye disease called wet age-related macular degeneration (wAMD). The purpose of the study is to find out how well different doses of a medicine called BI 836880 are tolerated.

Design: Single group, no masking

Number of Patients: 42

Inclusion Criteria: SRD part and MRD cohort 1 (treatment-resistant patients with wAMD): Men and women over the age of 55 with active choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD) despite anti-vascualr endothelial growth factor (VEGF) therapies (at least 3 prior injections with the last injection within 16 to 4 weeks before treatment). Active CNV secondary to AMD is to be defined either by recent fluorescein or optical coherence tomography (OCT) angiogram within 4 weeks prior to screening or fluorescein or OCT angiogram obtained prior to first anti VEGF-treatment to confirm the diagnosis and still active according to investigator judgement. For MRD part only: Central subfield retinal thickness >300 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) VA in the study eye between 75 and 24 letters inclusive (approximately 20/32 and 20/320 or 6/9.5 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. Male or female patients. Women of childbearing potential (WOCBP) cannot be included. Men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. 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. MRD cohort 2 (treatment-naive patients with wAMD): 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 BCVA and/or CSFT. Male or female patients. Women of childbearing potential (WOCBP) cannot be included. Men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. 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. Men and women over the age of 55 with treatment-naïve CNV secondary to AMD. Any CNV with subfoveal activity in the study eye defined as evidence of sub- and/or intraretinal fluid, or subretinal hyper-reflective material, or angiographic leakage. Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) VA in the study eye between 80 and 24 letters inclusive (approximately 20/25 and 20/320 or 6/7.5 and 6/95) at screening. Best-corrected ETDRS VA in the non-study eye 50 letters inclusive (approximately 20/100 or 6/30) or better at screening. If both eyes are eligible at screening, the study eye is the eye with the worse best-corrected VA. MRD cohort 3 (frequently treated patients): 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 and with the endorsement of the Sponsor, is able to prevent improvement in BCVA. Male or female patients. Women of childbearing potential (WOCBP)1 cannot be included. Men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. 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. Any CNV with subfoveal activity in the study eye defined as evidence of sub- and/or intraretinal fluid, or subretinal hyper-reflective material, or angiographic leakage. Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) VA in the study eye between 80 and 24 letters inclusive (approximately 20/25 and 20/320 or 6/7.5 and 6/95) at screening. If both eyes are eligible at screening, the study eye is the eye with the worse best corrected VA. Men and women over the age of 55 with diagnosed wAMD that: require frequent wAMD SoC (28-56 days between the last 3 treatments). have had ≥3 previous treatments with IVT SoC (ranibizumab, aflibercept, or bevacizumab) in the study eye. Had the last SoC injection ≥4 weeks, but no more than 8 weeks, before the first administration of the study drug. Have been on SoC treatment ≥6 months and are within 3 years from initial wAMD diagnosis in the study eye.

Exclusion Criteria: Additional eye disease in the study eye that could compromise best corrected VA (BCVA) with visual field loss, uncontrolled glaucoma (intraocular pressure (IOP) >24 mmHg on more than 2 consecutive measurements prior to screening), 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 SD-OCT. Any prior intraocular surgery in the study eye other then 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 1 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 (eg desferoximine, 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 haematology, blood chemistry, or urinalysis, if the abnormality defines a significant disease as defined in other exclusion criteria. Aspartate aminotransferase (AST) or alanine aminotransferase (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 glomerular filtration rate (GFR) < 30 mL/min. Significant alcohol or drug abuse within past 2 years per investigator judgement. Further exclusion criteria apply.

Information: clintriage.rdg@boehringer-ingelheim.com

Study: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of D-4517.2 after Subcutaneous Administration in Subjects With Neovascular (Wet) Age-related Macular Degeneration (AMD) or Subjects With Diabetic Macular Edema (DME) (Tejas)

Clinicaltrials.gov Identifier: NCT05387837

Sponsor: Ashvattha Therapeutics, Inc.

Purpose: A study to evaluate the safety, tolerability, and pharmacokinetics of D-4517.2 after subcutaneous administration in subjects with neovascular (wet) age-related macular degeneration (AMD) or subjects with diabetic macular edema (DME).

Design: Nonrandomized, parallel assignment, no masking

Number of Patients: 30

Inclusion Criteria: Overall study inclusion criteria-for all subjects: willing and able to give informed consent, comply with all study procedures, and be likely to complete the study. Demonstrated response to prior anti-VEGF treatment since diagnosis as defined by one or more of the following: (1) reduction of subretinal fluid or intraretinal fluid of greater than equal to 30% from initial diagnosis as measured by SD-OCT; (2) elimination of prior sub-foveal fluid from initial diagnosis as measured by SD-OCT; or (3) increase in BCVA of ≥2 lines from initial diagnosis using Snellen scale. Female subjects may be enrolled if they are: (1) not pregnant, lactating, or breastfeeding; (or 2) documented to be surgically sterile or postmenopausal. Female subjects of childbearing potential must practice true abstinence for at least 28 days prior to investigational product (IP) administration until 30 days after the last IP administration and have a negative serum and urine pregnancy test at screening and Baseline day 1, respectively, or use 2 forms of highly effective contraception, including 1 physical barrier (condom or diaphragm) plus another method, such as adequate hormonal method (eg, contraceptive implants, injectables, or oral contraceptives) or nonhormonal methods (eg, intrauterine device or spermicidals) from screening or at least 2 weeks prior to IP administration (whichever is earlier) until 30 days after the last IP administration and having a negative serum and urine pregnancy test at screening and Baseline day 1, respectively. Male subjects with female partners of childbearing potential may be enrolled if they are: documented to be surgically sterile (vasectomy), or practicing true abstinence for 30 days after the last IP administration, or using 2 adequate forms of highly effective contraception, 1 of which should be a physical barrier for 30 days after the last IP administration. Must agree not to donate sperm during study and for 30 days following administration of the last dose of IP.

Exclusion Criteria: history, within 6 months prior to screening, of any of the following medical conditions: myocardial infarction; any cardiac event requiring hospitalization; or treatment for acute congestive heart failure, transient ischemic attack, or stroke. Uncontrolled hypertension with systolic BP ≥160 mmHg and/or diastolic BP ≥95 mmHg (while patient at rest) at the screening visit. If the patient's initial reading exceeds these values, a second reading may be taken 30 minutes later on the same day. If the patient's BP is controlled by antihypertensive medication, the patient should be taking the same medication continuously for at least 30 days prior to day 1. Currently untreated diabetes mellitus or previously untreated subjects who initiated oral or injectable anti-diabetic medication within 3 months prior to day 1. Uncontrolled diabetes mellitus as defined by HbA1c >12%. Chronic renal disease requiring chronic hemodialysis or renal transplantation. Abnormal liver function, as defined by transaminase or total bilirubin 2 times above the upper limit of normal at the screening visit. Medical history of Wolff-Parkinson-White syndrome, family history of long QT, or on medication prolonging QT time or planned initiation during the trial. Known allergy to constituents of the study drug formulation, aflibercept, or clinically relevant hypersensitivity to fluorescein used by the patient during the study. Serious systemic infection: Any active infection for which systemic anti-infectives were used within 4 weeks before randomization. Recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject. Any organic or psychiatric disorder, or laboratory abnormality which, in the opinion of the investigator, will prevent the patient from completing the study activities as in the protocol or interfere with the interpretation of the study results. An underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious, or gastrointestinal) or history of other disease, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of study drug, might affect interpretation of the results of the study or which, in the opinion of the investigator, renders the patient at unacceptable risk of treatment complications by participating in the trial. Any major illness or surgical procedure within 1 month before screening. History of other diseases, physical examination finding, historical or current clinical lab finding giving reasonable suspicion of condition that contraindicates the use of the IP or that might affect the interpretation of the results of the study or renders the patient at high risk for treatment complications, in the opinion of the investigator. Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, or HIV type 1 and 2 antibodies. Prior/concomitant therapy: Participation in any investigational study within 30 days prior to screening, or planned use of an IP or device during the study; any exposure to a prior investigational drug product must be fully washed out (at least 5 half-lives). Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable study participant or unlikely to complete the trial. Use of systemic medications known to be toxic to the lens, retina or optic nerve (eg, deferoxamine, chloroquine/hydroxy-chloroquine, tamoxifen, phenothiazines, and ethambutol) used during the 6 month or 5 half-lives (whichever is longer) prior to day 1 or likely need to be used. Use of systemic immunomodulatory treatments (eg, interleukin-6 inhibitors) within 6 months or 5 half-lives (whichever is longer) prior to day 1. Use of systemic corticosteroids within 1 month prior to day 1. Systemic treatment for suspected or active systemic infection. Administration of systemic anti-VEGF or pro-VEGF treatment within 180 days or 5 half-lives, whichever is longer, before randomization visit. Any prior concomitant systemic anti-VEGF treatment within 6 months or 5 half-lives, whichever is longer, before randomization visit.

Information: bella@attx.com

Study: Pivotal 2 Study of RGX-314 Gene Therapy in Participants With nAMD (ASCENT)

Clinicaltrials.gov Identifier: NCT05407636

Sponsor: Regenxbio Inc.

Purpose: RGX-314 is being developed as a novel one-time gene therapy for the treatment of neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. Wet AMD is a significant cause of vision loss in the United States, Europe, and Japan, with up to 2 million people living with wet AMD in these geographies alone. Current anti-VEGF therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients. These therapies, however, require lifelong intraocular injections, typically repeated every 4 to 12 weeks in frequency, to maintain efficacy. Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time. RGX-314 is being developed as a potential one-time treatment for wet AMD.

Design: Randomized, parallel assignment, single masking

Number of Patients: 465

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: Study of the Safety of Use of Intravitreal SOK583A1 Provided in a Vial Kit

Clinicaltrials.gov Identifier: NCT05282004

Sponsor: Sandoz

Purpose: This is a single-arm, open-label study where all patients will receive a single injection of SOK583A1 (40 mg/mL) provided in a vial kit at baseline. The total study duration for the individual participant is approximately 31 days.

Design: Single group, no masking

Number of Patients: 38

Inclusion Criteria: Patients ≥50 years of age at baseline. Patients diagnosed with nAMD (uni- or bilateral). Patients already under IVT Eylea treatment (last injection of the induction period or maintenance phase). Willing and able to comply with all study procedures, and be likely to complete the study. Signed informed consent must be obtained before any assessment is performed

Exclusion Criteria: Active, suspected or recent (within 4 weeks) intraocular inflammation (grade trace or above) in the study eye at baseline, which is of clinical significance according to the investigator's judgment, such as active infections of the anterior segment; this includes conjunctivitis (except mild blepharitis), keratitis, scleritis, idiopathic or autoimmune associated uveitis or endophthalmitis. Any uncontrolled ocular hypertension or glaucoma in the study eye (defined as IOP ≥26 mmHg, despite treatment with anti-glaucomatous medication). History of a medical, ocular or nonocular condition, that in the judgment of the investigator, would preclude a safe administration of investigational product. Visual acuity score (VAS) worse than 20/200 on a Snellen chart, the generally accepted level of legal blindness. Topical ocular corticosteroids administered for at least 30 consecutive days within 3 months prior to screening. Systemic treatment with long-acting corticosteroids (more than 10 mg prednisolone equivalent) within 3 months prior to screening 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. Any invasive intraocular surgery, prior long-acting therapeutic agent, or ocular drug release device implantation (approved or investigational) in the study eye any time during the past 3 months. Receipt of any systemic anti-VEGF within the last 6 months prior to enrollment. Uncontrolled hypertension (defined as a systolic value ≥160 mmHg or diastolic value ≥100 mmHg at screening). Participants who do not comply with the local COVID-19 regulations of the study site.

Information: novartis.email@novartis.com

Study: Study of EYP-1901 in Subjects With Wet Age-related Macular Degeneration (wAMD)

Clinicaltrials.gov Identifier: NCT05381948

Sponsor: EyePoint Pharmaceuticals, Inc.

Purpose: This is a phase 2 randomized, double-masked study comparing the efficacy of EYP-1901 at 2 dose levels: 2060 µg and 3090 µg against aflibercept.

Design: Randomized, parallel assignment, triple masking

Number of Patients: 150

Inclusion Criteria: Documented diagnosis of wAMD in the study eye, with disease onset within 9 months prior to the screening visit. Previously treated with at least 2 anti-VEGF intravitreal injections (ie, bevacizumab, ranibizumab, or aflibercept) for wAMD per standard of care in the study eye within 6 months prior to the screening visit. BCVA ETDRS letter score of 35 letters (20/200 Snellen equivalent) to 80 letters (20/25 Snellen equivalent) in the study eye at the screening visit and on day 1.

Exclusion Criteria: Central subfield thickness (CST) >400 µm in the study eye at the screening visit or day 1. Any concurrent intraocular condition in the study eye (eg, cataract or glaucoma). Historical or active intraocular inflammation (grade trace or above) in the study eye, other than expected findings from routine cataract surgery.

Information: dpaggiarino@eyepointpharma.com

Study: Safety and Efficacy of ADVM-022 in Treatment-experienced Patients With Neovascular Age-related Macular Degeneration

Clinicaltrials.gov Identifier: NCT05536973

Sponsor: Adverum Biotechnologies, Inc.

Purpose: Neovascular or wet age-related macular degeneration (nAMD) is a degenerative ocular disease associated with the infiltration of abnormal blood vessels in the retina from the underlying choroid layer and is a leading cause of blindness in patients over 65 years of age. The abnormal angiogenic process in nAMD is stimulated and modulated by vascular endothelial growth factor (VEGF). Treatment of nAMD requires frequent intravitreal (IVT) injections of VEGF inhibitors (anti-VEGF) administered every 4-12 weeks. ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product being developed for the treatment of nAMD, and offers the potential for sustained intraocular expression of aflibercept following a single IVT injection. ADVM-022 is designed to reduce the current treatment burden which often results in undertreatment and vision loss in patients with nAMD receiving anti-VEGF therapy in clinical practice.

Design: Randomized, parallel assignment

Number of Patients: 72

Inclusion Criteria: Male or female participants, age ≥50 years of age; willing and able to provide written, signed informed consent for this study; demonstrated a meaningful response to anti-VEGF therapy. Current evidence of active primary or recurrent sub-foveal choroidal neovascularization (CNV) assessed by spectral domain optical coherence tomography (SD-OCT); subjects must be under active anti-VEGF treatment for wet AMD and received a minimum of 2 injections within 4 months prior to screening; BCVA ETDRS Snellen equivalent between ≤20/32 and ≥20/320.

Exclusion Criteria: Any condition that could affect the interpretation of results or render the participant at high risk of treatment complications in the opinion of the investigator; ocular or periocular infection or intraocular inflammation in either eye within 1 month prior to or at the randomization visit (day -7); uncontrolled diabetes or HbA1c ≥7.0 %; history or evidence of significant uncontrolled concomitant disease within 6 months of the screening visit; history within the 12 months prior to screening or evidence of renal or hepatic dysfunction at screening; any history of ongoing bleeding disorders or INR >3.0; history or evidence of macular or retinal disease other than nAMD; active or history of retinal detachment or retinal pigment epithelium rip/tear; uncontrolled ocular hypertension or glaucoma; prior treatment with photodynamic therapy or retinal laser for the treatment of nAMD; any history of vitrectomy or any other vitreoretinal surgery within 3 months prior to the randomization visit (day -7)

Prior treatment with gene therapy.

Information: LUNA-Clinops@adverum.com

Study: Safety and Efficacy of AM712 in Patients With nAMD

Clinicaltrials.gov Identifier: NCT05345769

Sponsor: AffaMed Therapeutics (US) Inc.

Purpose: The purpose of this phase 1 study is comprised of multiple ascending-dose component (Part 1) and dose-expansion cohorts component (Part 2) to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in patients with neovascular age-related macular degeneration (nAMD).

Design: Single group, open label

Number of Patients: 24

Inclusion Criteria: Male or female subjects 50 years of age or older. Active sub-foveal CNV lesion secondary to nAMD including juxta- or extra-foveal lesions that partially affect the fovea. The area of CNV must occupy at least 50% of total lesion. Total lesion area ≤12 DA. ETDRS BCVA letter score measured at screening and BSL. Clear ocular media and adequate pupil dilation to permit good quality photographic imaging in study eye.

Exclusion Criteria: Any previous systemic anti-VEGF treatment. Any systemic treatment or therapy to treat neovascular AMD. Continuous use of systemic corticosteroids. Diseases that affect intravenous injection and venous blood sampling. Presence of CNV due to other causes, such as ocular histoplasmosis, trauma, multifocal choroiditis, angioid streaks, history of choroidal rupture, or pathologic myopia in study eye. History or any concurrent ocular condition which, in opinion of investigator, could either confound interpretation of efficacy and safety of IP or require medical or surgical intervention. Scar, fibrosis, RPE tear, or atrophy involving foveal center or area of fibrosis occupy ≥50% of total lesion area in study eye. Evidence of myopia degeneration, diagnosis supported by the axial length examination in study eye. History or any concurrent macular abnormality other than AMD in study eye. Current vitreous hemorrhage or history of vitreous hemorrhage in study eye. History of recurrent inflammation in study eye. Subject having out of range laboratory values defined as: ALT or AST >2 x ULN, total bilirubin >1.5 x ULN Serum creatinine >1.5 x ULN, BUN >2 x ULN.

Information: fan.yang@affamed.com

Study: Phase 3 Study Assessing the Efficacy, Safety, and Immunogenicity of SOK583A1 vs Eylea in Patients With Neovascular Age-related Macular Degeneration (Mylight)

Clinicaltrials.gov Identifier: NCT04864834

Sponsor: Sandoz

Purpose: To demonstrate similar efficacy, safety, and immunogenicity of SOK583A1 and Eylea EU as per Eylea-approved treatment regimen in patients with nAMD.

Design: Randomized, parallel assignment, double masked

Number of Patients: 460

Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Participants must be 50 years of age or older at screening. Anti-VEGF treatment-naïve patients for either eye and systemically. Study eye diagnosed with active CNV lesions (type 1 and/ or type 2) secondary to AMD and/or retinal angiomatous proliferation lesions (type 3), affecting the central subfield. Active CNV lesion is defined by the presence of leakage as evidenced by fluorescein angiography, and intra- or subretinal fluid as evidenced by optical coherence tomography, both confirmed by the CRC at screening. Total area of CNV (including both classic and occult components) must comprise >50% of the total lesion area in the study eye, confirmed by the CRC at screening. BCVA between 73 and 38 letters, both inclusive, in the study eye at screening and Baseline using ETDRS testing charts. Willing and able to comply with all study procedures and be likely to complete the study. Clear ocular media and adequate pupil dilatation in both eyes to permit good quality photographic imaging.

Exclusion Criteria: Ocular conditions and treatments: Previous treatment with any anti-VEGF therapy in either eye or investigational drugs in study eye or fellow eye, at any time prior to baseline. Participant has received any approved treatment for nAMD (other than vitamin and dietary supplements) in the study eye and at any time prior to baseline. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of -8.0 D 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. Any active or suspected intraocular or periocular infection or suspected active intraocular inflammation (eg, infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in either eye at screening or baseline. 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 CRC prior to randomization. Subretinal hemorrhage that is ≥50% of the total lesion area in the study eye, or if the subretinal hemorrhage involving the fovea is 1 or more disc areas (≥2.54 mm²) in size in the study eye, as assessed by fluorescein angiography (FA) and confirmed by the CRC. Retinal pigment epithelium (RPE) rip/tear in the study eye at screening or baseline. Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to baseline. History or evidence of the following, in the study eye: Intraocular (including cataract surgery) or refractive surgery within the 90-day period prior to Baseline. The yttrium aluminum garnet (YAG) posterior capsulotomy is allowed no later than 4 weeks prior to baseline. Previous penetrating keratoplasty or vitrectomy. Previous panretinal photocoagulation. Previous photodynamic therapy. Previous submacular surgery or other surgical intervention for AMD. Retinal detachment or treatment or surgery for retinal detachment. Any history of macular hole of stage 2 and above. Prior trabeculectomy or other filtration surgery. Ocular trauma within the 6-month period prior to baseline. History of hypersensitivity to any of the study treatments or its excipients, or clinically relevant sensitivity to fluorescein dye, as assessed by the investigators. 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. Aphakia and/or absence of the posterior capsule in the study eye at screening or Baseline, unless it occurred as a result of a YAG posterior capsulotomy in association with prior posterior chamber intraocular lens implantation. Intra- or periocular use of corticosteroids in the study eye within a 6-month period prior to baseline. Use of topical ocular corticosteroids in the study eye for 30 or more consecutive days within the 90 day period prior to baseline. Previous therapeutic radiation near the region of the study eye. Concomitant conditions or ocular disorders in the study eye, including media opacities, cataract, and diabetic macular edema, at screening or Baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results (efficacy and safety), compromise visual acuity, or require medical or surgical intervention during the course of the study. Presence of amblyopia, amaurosis or ocular disorders with BCVA <38 letters (ETDRS testing charts) in the fellow eye at screening (except when due to conditions whose surgery may improve VA, eg, cataract). Presence of scleromalacia in either eye. Participants requiring anti-VEGF treatment of the fellow eye at baseline will not be eligible for the PK substudy. Systemic conditions and treatments: Previous systemic treatment with any anti-VEGF therapy. Use of systemic corticosteroids for 30 or more consecutive days within the 90 days prior to Baseline, with the exception of low stable doses of corticosteroids (defined as ≤10 mg prednisolone or equivalent dose used for 90 days or more). Uncontrolled blood pressure defined as a systolic value ≥160 mmHg or diastolic value ≥100 mmHg at screening. Stroke or myocardial infarction during the 6-month period prior to Baseline. Participation in an investigational systemic drug, biologic, or device study within 30 days or duration of 5 half-lives of the investigational product (whichever is longer) prior to baseline. Note: observational clinical studies solely involving over-the-counter vitamins, supplements, or diets are not exclusionary. Presence of infection at screening or active infection within 2 weeks before screening. Underlying advanced, severe, and uncontrolled concomitant condition (including, but not limited to, metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, inflammatory, infectious, or gastrointestinal), physical examination finding, or clinical laboratory finding which in the opinion of the investigator place the participant at unacceptable risk from participation in the study. History of a medical condition (including, but not limited to chronic disease immunosuppression, metabolic dysfunction, prior exposure to other drugs that may pose risk of infection or allergic reactions) that, in the judgment of the investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product, or that might affect participant safety or interpretation of the study results. Pregnant or nursing (lactating) women and women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 3 months after stopping the medication. Highly effective contraception methods include: Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.), female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment. Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant. Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS).

Information: novartis.email@novartis.com

Study: Study Evaluating the Treatment of OTX-TKI for Subjects With Neovascular Age-related Macular Degeneration

Clinicaltrials.gov Identifier: NCT04989699

Sponsor: Ocular Therapeutix, Inc.

Purpose: Evaluate the safety, tolerability, and efficacy of OTX-TKI for intravitreal use in subjects with neovascular age-related macular degeneration.

Design: Randomized, parallel assignment, triple masked

Number of Patients: 20

Inclusion Criteria: Have a diagnosis, within 3 years of screening, of previously treated subfoveal neovascularization (SFNV) secondary to nAMD with leakage involving the fovea, previously treated with documented evidence of an initially favorable clinical response to anti-VEGF therapy (ie, aflibercept, ranibizumab, brolucizumab, or bevacizumab). The macular appearance on OCT is considered to be free of excess intraretinal and/or subretinal fluid as judged by the investigator. Must have received at least 3 anti-VEGF injections in the past year. Have received the most recent anti-VEGF injection within the past 1 to 4 weeks prior to screening visit. BCVA ETDRS score between 24 and 83 letters (~20/25 to ~20/320 Snellen equivalent).

Exclusion Criteria: Have evidence of a scar, fibrosis, or atrophy of >50% of the total lesion in the study eye. Have presence of a disease other than choroidal neovascular membrane (CNVM) due to AMD in the study eye that could affect vision or safety assessments. Have monocular vision (fellow eye Snellen BCVA is 20/200 or worse.

Information: clinicalaffairs@ocutx.com

Study: A Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 Compared With Intravitreal Aflibercept in Participants With Neovascular (Wet) Age-related Macular Degeneration (wAMD) (DAYLIGHT)

Clinicaltrials.gov Identifier: NCT04964089

Sponsor: Kodiak Sciences Inc

Purpose: This phase 3 study will evaluate the efficacy and safety of KSI-301 compared to aflibercept, in participants with neovascular (wet) age-related macular degeneration (wAMD).

Design: Randomized, parallel assignment, triple masked

Number of Patients: 500

Inclusion Criteria: Signed informed consent prior to participation in the study. Treatment-naïve choroidal neovascularization (CNV) secondary to AMD. BCVA ETDRS score between 83 and 25 letters, inclusive, in the study eye. Decrease in vision in the study eye determined by the investigator to be primarily the result of wAMD. Other protocol-specified inclusion criteria may apply.

Exclusion Criteria: BCVA of hand motion or worse in the non-study eye or nonphysical presence of a non-study eye (ie, monocular). Active or suspected ocular or periocular infection or inflammation. CNV secondary to other causes in the study eye. Any history or evidence of a concurrent ocular condition present in the study eye, 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. Uncontrolled glaucoma in the study eye. Significant media opacities, including cataract, in the study eye that might interfere with visual acuity, assessment of safety, or OCT or fundus photography. Cataract in the study eye that in the judgment of the investigator is expected to require surgical extraction within 12 months of screening. Women who are pregnant or lactating or intending to become pregnant during the study. 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. Uncontrolled blood pressure defined as a systolic value ≥180 mmHg or diastolic value ≥100 mmHg while at rest. Other protocol-specified exclusion criteria may apply.

Information: ksi301clinical@kodiak.com

Study: Safety, Tolerability, and Efficacy Study of UBX1325 in Patients With Neovascular Age-related Macular Degeneration (AMD)

Clinicaltrials.gov Identifier: NCT05275205

Sponsor: Unity Biotechnology, Inc.

Purpose: This study is intended to assess safety, tolerability, and biological activity of a repeat IVT injection of UBX1325 in patients with wet AMD.

Design: Parallel assignment, double masking

Number of Patients: 46

Inclusion Criteria: Patients aged ≥50 years. Active CNV associated with age-related macular degeneration as evidenced on FA and SD-OCT with presence of intraretinal or subretinal fluid at screening and day 1. BCVA in the study eye (most affected) of 70 to 20 ETDRS letters (equivalent to 20/40 to 20/400 on the Snellen chart) at 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: Concurrent disease in the study eye or structural damage, other than wet AMD, that could compromise BCVA, prevent BCVA improvement, require medical or surgical intervention during the study period, confound interpretation of the results, or interfere with assessment of toxicity or CFP in the study eye. Any ocular/intraocular/periocular infection or inflammation in either eye. Subretinal hemorrhage with bleeding area of 4 or greater disc area in the study eye. History of vitreous hemorrhage in the study eye within 2 months prior to screening. Any condition, including laboratory findings and findings in the medical history or in the prestudy assessments, that, in the opinion of the investigator, constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation or prevent the patient from fully participating in all aspects of the study. Significant media opacities, including cataract, which might interfere with VA, assessment of toxicity, or fundus imaging

Information: UBX1325_medicalmonitor@unitybiotechnology.com

Study: 4D-150 in Patients With Neovascular (Wet) Age-related Macular Degeneration

Clinicaltrials.gov Identifier: NCT05197270

Sponsor: 4D Molecular Therapeutics

Purpose: Phase 1/2 dose-escalation and randomized, controlled, masked expansion trial in adults with wet AMD undergoing active anti-VEGF treatment.

Design: Randomized, sequential assignment

Number of Patients: 65

Inclusion Criteria: Greater than or equal to 50 years of age. Diagnosed with CNV secondary to AMD. BCVA ETDRS Snellen equivalent for dose escalation between ~20/50 and ~20/320 (sentinel subjects only) or ~20/32 and ~20/320, or for dose expansion ~20/25 and~20/200. Currently receiving anti-VEGF treatment in the study eye (minimum of 6 injections within the last 12 months) and has demonstrated a clinical response consistent with anti-VEGF activity within 12 months prior to screening.

Exclusion Criteria: Fibrosis, atrophy, or retinal pigment epithelial tear in the center of the fovea in the study eye, or any condition preventing visual acuity improvement. Prior treatment with photodynamic therapy or retinal laser. History of uveitis in either eye. Any other pre-existing eye conditions or surgical complications that would preclude participation in an interventional clinical trial or interfere with the interpretation of study endpoints.

Information: clinicaltrials@4DMT.com

Study: A 3-month Study to Compare the Safety of ONS-5010 in Vials vs Prefilled Syringe in Subjects With Visual Impairment due to Retinal Disorders (NORSE SEVEN)

Clinicaltrials.gov Identifier: NCT05112861

Sponsor: Outlook Therapeutics, Inc.

Purpose: The study will compare the safety of ophthalmic bevacizumab in vials vs prefilled syringes 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: Randomized, parallel assignment

Number of Patients: 120

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. Previous use of Beovu. 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.

Study: Optical Coherence Tomography Angiography (OCTA)–directed PDT Triple Therapy

Clinicaltrials.gov Identifier: NCT04075136

Sponsor: Wake Forest University Health Sciences

Purpose: Optical coherent tomography angiography (OCTA)–directed PDT triple therapy for treatment-naïve patients with exudative age-related macular degeneration (AMD) vs standard of care anti-VEGF monotherapy.

Design: Randomized, parallel assignment

Number of Patients: 150

Inclusion Criteria: Willing to give written informed consent. Willing and able to comply with all study procedures for the duration of the study. Presence of exudative AMD with evidence of choroidal neovascularization: type 1, 2, and/or 3 on spectral domain OCT, fluorescein angiography, indocyanine green angiogram, and optical coherent tomography angiography. Visual Acuity of 20/25 to 20/400 at screening and Baseline visits using an autorefractor or Early Treatment Diabetic Retinopathy Study chart. Intraocular pressure ≤25 mmHg. Females of childbearing potential that are willing to use medically acceptable methods of birth control.

Exclusion Criteria: Exudation maculopathies without drusen. Previous treatment with macular photocoagulation, anti-VEGF medication, or PDT with Visudyne. Myocardial infarction or cerebrovascular accident within the last 6 weeks. Previous vitrectomy. Optic neuropathy. Diabetic retinopathy. Traction maculopathies. Allergies to fluorescein and indocyanine, dilating agents or anti-VEGF medications. Have received previous treatment for AMD. Any uncontrolled condition or illness that in the opinion of the investigator makes the subject unsuitable for the study.

Information: angmitch@wakehealth.edu

Study: A Study of the Efficacy and Safety of the Port Delivery System With Ranibizumab in Patients With Neovascular Age-related Macular Degeneration Previously Treated With Intravitreal Agents Other Than Ranibizumab (Belvedere)

Clinicaltrials.gov Identifier: NCT04853251

Sponsor: Genentech Inc.

Purpose: Study ML43000 is a phase 3b/4 multicenter, open-label (visual assessor-masked) study designed to assess the efficacy and safety of PDS 100 mg/mL Q24W in patients with nAMD who have been previously treated with anti-VEGF agents other than ranibizumab. Approximately 200 patients will be enrolled at approximately 40 sites.

Design: Single group assignment, no masking

Number of Patients: 200

Inclusion Criteria: Ocular Inclusion Criteria: Initial diagnosis of nAMD within 6 to 18 months prior to the signing of the ICF. Previous treatment with at least 3 anti-VEGF injections other than ranibizumab for nAMD per standard of care in the 9 months prior to PDS implantation; the most recent anti-VEGF injection must have occurred within 12 weeks of PDS implantation. The last 2 anti-VEGF injections for nAMD prior to PDS implantation must be with the same eligible anti-VEGF agent, either bevacizumab or aflibercept. Availability of historical visual acuity data and SD-OCT imaging prior to the first anti-VEGF treatment for nAMD until the time of study enrollment. Availability of comprehensive historical anti-VEGF injection data including anti-VEGF agent administered and date of administration from the first anti-VEGF treatment for nAMD until the time of study enrollment. Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis BCVA of 34 letters (approximate 20/200 Snellen equivalent) or better, using ETDRS chart at a starting distance of 4 meters (see the BCVA manual for additional details) at screening and enrollment visits. All subtypes of nAMD lesions are permissible. nAMD lesions at the time of diagnosis must involve the macula (6 mm diameter centered at the fovea). Sufficiently clear ocular media and adequate pupillary dilation to allow for clinical exam and analysis and grading by the central reading center of SD-OCT images

Exclusion Criteria: Study Eye: Prior vitrectomy surgery, submacular surgery, or other surgical intervention for AMD. Prior pars plana vitrectomy surgery. Prior treatment with ranibizumab. Prior treatment with verteporfin for injection, external-beam radiation therapy, or transpupillary thermotherapy. Previous treatment with corticosteroid intravitreal injection. Previous intraocular device implantation excluding intraocular lenses. Previous intraocular surgery (including cataract surgery) within 3 months of study enrollment. Previous laser (any type) used for AMD treatment. History of vitreous hemorrhage. History of rhegmatogenous retinal detachment. History of glaucoma filtering surgery, tube shunts, or microinvasive glaucoma surgery. History of corneal transplant. History of conjunctival surgery in the superotemporal quadrant. Prior participation in a clinical trial involving any intravitreal anti-VEGF agents. Subretinal hemorrhage that involves the center of the fovea. Subfoveal fibrosis or subfoveal atrophy Retinal pigment epithelial tear. Any concurrent intraocular condition (eg, cataract, glaucoma, diabetic retinopathy, or epiretinal membrane) that would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results. Rhegmatogenous retinal tears or peripheral retinal breaks on depressed fundus exam that are untreated, or treated within the 3 months prior to study enrollment. Aphakia or absence of the posterior capsule. Previous violation of the posterior capsule is also an exclusion criterion unless it occurred as a result of yttrium-aluminum garnet (YAG) laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation. Spherical equivalent of the refractive error demonstrating more than 8.0 D of myopia or evidence of pathologic myopia on depressed fundus examination. Preoperative refractive error that exceeds 8.0 D of myopia, for patients who have undergone prior refractive or cataract surgery. Spherical equivalent of the refractive error demonstrating more than 5.0 D of hyperopia. Preoperative refractive error that exceeds 5.0 D of hyperopia, for patients who have undergone prior refractive or cataract surgery. Uncontrolled ocular hypertension or glaucoma. Scleral pathology in the superotemporal quadrant. Conjunctival pathologies in the superotemporal quadrant. History or presence of severe posterior blepharitis, recurrent chalazia or hordeolum, severe dry eye syndrome, or severe allergic conjunctivitis. Ectropion, entropion or other impairment of the upper or lower eyelid impacting lid functionality needed to protect the ocular surface from exposure. Trichiasis. Corneal neuropathy. Lagophthalmos or incomplete blink. Active or history of facial nerve palsy/paresis. Either Eye: Prior treatment with brolucizumab (at any time prior to screening visit). Prior treatment with any anti-VEGF biosimilar agents (at any time prior to screening visit). Prior treatment with external-beam radiation therapy or brachytherapy. MNV due to causes such as ocular histoplasmosis, trauma, or pathologic myopia. MNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia MNV masquerading lesions (eg, cone dystrophy, adult vitelliform dystrophy, pattern dystrophy). Any active or history of uveitis (eg, idiopathic, drug-associated or autoimmune-associated). Active or history of keratitis, scleritis, or endophthalmitis. Suspected or active ocular or periocular infectious conjunctivitis or endophthalmitis. Active or history of Sjogrens syndrome or keratoconjunctivitis sicca. Active or history of floppy eyelid syndrome. Active or history of chronic eye rubbing. Active thyroid eye disease. Concurrent Systemic Conditions: Uncontrolled blood pressure. Active or history of autoimmune diseases. 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 patient at high risk of treatment complications, in the opinion of the investigator. Current active systemic infection. Use of any systemic anti-VEGF agents. Chronic use of oral corticosteroids. Active cancer within 12 months of enrollment except. Previous participation in any nonocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent. Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of the enrollment visit. Pregnant or breastfeeding.

Information: global-roche-genentech-trials@gene.com

Study: RGX-314 Gene Therapy Pharmacodynamic Study for Neovascular Age-related Macular Degeneration (nAMD)

Clinicaltrials.gov Identifier: NCT04832724

Sponsor: Regenxbio Inc.

Purpose: RGX-314 is a gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein. RGX-314 is being studied for its potential to have a single injection that could allow the eye to make its own supply of anti-VEGF continually. The purpose of this phase 2, open label study is to evaluate whether different doses of RGX-314 from 2 different formulations (clinical vs eventual commercial formulation) perform the same in humans when delivered by subretinal administration.

Design: Nonrandomized, sequential assignment, no masking

Number of Patients: 60

Inclusion Criteria: Males or females, aged ≥50 years and ≤89 years. An Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA letter score between ≤78 and ≥40 in the study eye at screening. Diagnosis of subfoveal choroidal neovascularization (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. Any condition in the investigator's opinion that could limit visual acuity improvement in the study eye. Active or history of retinal detachment or retinal tear in the study eye. Advanced glaucoma in the study eye. Received any gene therapy. Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months.

Information: patientadvocacy@regenxbio.com

Study: OPT-302 With Ranibizumab in Neovascular Age-related Macular Degeneration (nAMD) (ShORe)

Clinicaltrials.gov Identifier: NCT04757610

Sponsor: Opthea Limited

Purpose: A 2-year, phase 3, multicenter, randomized, parallel-group, sham-controlled, double-masked study. Primary efficacy will be determined at week 52.

Design: Randomized, parallel assignment, quadruple masking

Number of Patients: 990

Inclusion Criteria: Active subfoveal CNV lesion or juxtafoveal CNV lesion with foveal involvement that is secondary to AMD in the study eye. An ETDRS BCVA score between 60 and 25 (inclusive) letters in the study eye.

Exclusion Criteria: Any previous treatment for neovascular AMD. Clinically significant ocular disorders (other than neovascular AMD), which may interfere with assessment of BCVA, assessment of safety, or fundus imaging. Any current (or history of a) social, psychological, or medical condition that precludes enrolment into the study.

Information: info@opthea.com

Study: OPT-302 With Aflibercept in Neovascular Age-related Macular Degeneration (nAMD) (COAST)

Clinicaltrials.gov Identifier: NCT04757636

Sponsor: Opthea Limited

Purpose: A 2-year phase 3, multicenter, randomized, parallel-group, sham-controlled, double-masked study. Primary efficacy will be determined at week 52.

Design: Randomized, parallel assignment, quadruple masking

Number of Patients: 990

Inclusion Criteria: Active subfoveal CNV lesion or juxtafoveal CNV lesion with foveal involvement that is secondary to AMD in the study eye. An ETDRS BCVA score between 60 and 25 (inclusive) letters in the study eye.

Exclusion Criteria: Any previous treatment for neovascular AMD. Clinically significant ocular disorders (other than neovascular AMD), which may interfere with assessment of BCVA, assessment of safety, or fundus imaging. Any current (or history of a) social, psychological, or medical condition that precludes enrolment into the study.

Information: info@opthea.com

Study: A Study to Evaluate the Long-term Safety and Tolerability of Faricimab in Participants With Neovascular Age-related Macular Degeneration (AVONELLE-X)

Clinicaltrials.gov Identifier: NCT04777201

Sponsor: Hoffmann-La Roche

Purpose: This is a multicenter long-term extension study designed to evaluate the long-term safety and tolerability of faricimab 6 mg administered by intravitreal injection at a personalized treatment interval to participants with neovascular age-related macular degeneration who enrolled in and completed one of the phase 3 studies: GR40306 (NCT03823287) or GR40844 (NCT03823300), also referred to as the parent studies. Eligible patients who consent to participate in this study will be enrolled upon completion of the end-of-study visit in the parent study.

Design: Single group, no masking

Number of Patients: 1,280

Inclusion Criteria: Previous enrollment in and completion of Study GR40306 (NCT03823287) or Study GR40844 (NCT03823300), without study or study drug discontinuation. For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs. Women must remain abstinent or use contraceptive methods with a failure rate of <1% per year during the treatment period and for 3 months after the final dose of faricimab. Women must refrain from donating eggs during the same period.

Exclusion Criteria: Pregnant or breastfeeding, or intending to become pregnant during the study or within 28 days after the final dose 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-related procedure preparations, 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.

Information: global-roche-genentech-trials@gene.com

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 Compare 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 treat neovascular AMD in the study eye, except dietary supplements or vitamins. Fellow eye shows signs 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, fibrosis, or atrophy in the study eye. Presence of retinal pigment epithelial tears or rips involving the macula 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 of, 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: 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 vs placebo on the anatomic and functional outcomes in persistent subretinal eye fluid in neovascular wet age-related macular degeneration. This subset are incomplete or nonresponders 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 subretinal with or without intraretinal 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 (eg, 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 6 and 9 month time points after recruitment; Missing 2 or more consecutive injections during the 6-month 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 (eg, 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 mmHg or diastolic blood pressure >110 mmHg; 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 (ie, 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 the 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 vs 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 (22.86 mm², 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 8.0 D 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, ie, 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: 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 8.0 D 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

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 to 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: 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 -6 D 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: 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 after 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 >100×10³/µL; eGFR >30 mL/min/1.73 m²; 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: The Study of CU06-1004 in Patients With Diabetic Macular Edema (DME)

Clinicaltrials.gov Identifier: NCT05573100

Sponsor: Curacle Co., Ltd.

Purpose: This phase 2a trial is a randomized, open-label, parallel-group study in approximately 60 patients with DME to evaluate the efficacy and safety of CU06-1004 orally administered once daily for 12 weeks. The study will have a 1:1:1 randomization (CU06-1004 100mg: CU06-1004 200mg: CU06-1004 300mg).

Design: Randomized, parallel assignment, no masking

Number of Patients: 60

Inclusion Criteria: Subject who is male or female ≥18 years of age. Subject who has a diagnosis of type 1 or 2 diabetes mellitus. 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. Subject who has study eye with CST of ≥320μm on SD-OCT within 8 days of randomization. Subject who has DRSS score ≥47. Subject who has study eye with an ETDRS BCVA letter score ranging from 34 to 83, inclusive (approximate Snellen equivalent of 20/25 - 20/200 at a distance of 4 meters). Subject who has media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus photographs.

Exclusion Criteria: Subject whose macular edema is of non-diabetic retinopathy etiology (eg, secondary to vitreomacular interface abnormalities). Subject who has had major surgery within 3 months prior to randomization or major surgery planned during the next 6 months. Subject who has a hypersensitivity to any excipients of the investigational product or similar class of drug and ingredient. Subject who has the following illness or abnormal laboratory test values: Uncontrolled hypertension (SBP >180 mmHg or DBP >100 mmHg); Uncontrolled diabetes (HbA1c >11.0%); ANC < 1.5 × 109/L; Platelet < 125 × 109/L; Total bilirubin >1.5 × ULN; AST or ALT >2 × ULN; CrCl < 40 mL/min < Cockcroft-Gault formula >CrCl (male) = ([140 - age] * weight in kg) / (serum creatinine * 72) CrCl (female) = CrCl (male) * 0.85; Positive results for HIV or Hepatitis B or C viruses. Subject who participated in an investigational trial within 3 months of randomization that involved treatment with any drug that has not received regulatory approval at the time of study entry. Subject who has received gene therapy for any indication. Subject who has received COVID-19 vaccine within 30 days of first dosing until the end of the study. Pregnant woman, lactating woman, or female or male subject of childbearing potential who doesn't accept appropriate contraceptive measures for the next 6 months. *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, or FemCap). Subject who has medical condition that, in the opinion of the investigator, would preclude participation in the study (eg, unstable medical status including blood pressure, cardiovascular disease, and glycemic control). Subject who administered vaccinium myrtillus extract or dobesilate calcium within 2 weeks before randomization. Subject who has unstable angina, myocardial infarction, transient ischemic attack, cerebral infarction, coronary artery bypass surgery, or transluminal coronary angioplasty within 6 months before screening. Subject who has an ocular condition (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, Irvine-Gass Syndrome, foveal atrophy, pigmentary changes, dense subfoveal hard exudates, nonretinal condition etc.). Subject who has exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis. Subject who is expected to have no improvement of decreased visual acuity in the opinion of the Investigator, even if macular edema is resolved (eg, foveal atrophy, abnormal pigmentation, dense subfoveal hard exudate). Subject who has a history of treatment with anti-VEGF agents, focal laser treatment (Focal/grid laser photocoagulation), or any other treatment within 3 months prior to study entry or intravitreal dexamethasone or triamcinolone within 6 months prior to study entry. Subject who has a history of treatment with intravitreal fluocinolone astonide. Subject who has a history of panretinal scatter photocoagulation (PRP). Subject who anticipated need for PRP in the 3 months following randomization. Subject who has a history of ocular surgery (including cataract extraction, any intraocular surgery, etc.) within prior 6 months or anticipated within the next 6 months following randomization. Subject who has a history of retinal detachment or retinal detachment repair surgery. Subject who has a history of YAG capsulotomy performed within 2 months prior to randomization. Subject who has uncontrolled glaucoma in either eye (intraocular pressure (IOP) >24 mmHg on medication or according to the investigator's judgment). Subject who has a history of vitrectomy. Subject who has any active intraocular inflammatory diseases such as uveitis, conjunctivitis, and in either eye. Subject who has any history of intraocular inflammation in either eye other than what would be expected in the normal post-operative course following prior routine ocular surgery such as cataract surgery.

Information: christinelee@kcrnresearch.com

Study: Phase 2 Study to Evaluate the Safety and Efficacy of OPL-0401 in Patients With Non-proliferative Diabetic Retinopathy (Spectra)

Clinicaltrials.gov Identifier: NCT05393284

Sponsor: Valo Health, Inc.

Purpose: OPL-0401-201 is a multicenter study to investigate the efficacy and safety of OPL-0401 in patients with diabetes mellitus (DM) with diabetic retinopathy.

Design: Randomized, parallel assignment, triple masking

Number of Patients: 120

Inclusion Criteria: Adults ≥18 years; Diabetes mellitus (type 1, type 2, or other forms); Females who are not a woman of childbearing potential (WOCBP) or who agree to use contraception; At least one eye with moderately severe to severe NPDR (DRSS levels 47 or 53); Patients with diabetic macular edema (DME) may be eligible if they meet protocol-specified eligibility criteria; Best-corrected visual acuity (BCVA) early treatment of diabetes retinopathy study (ETDRS) letter score at screening ≥69 letters (approximate Snellen equivalent of 20/40 or better) in the study eye without CI-DME, or ≥75 letters when CI-DME is present (approximate Snellen equivalent 20/32 or better); Anti–vascular endothelial growth factor (VEGF) or any laser treatment is not required nor anticipated in either eye for least 6 months.

Exclusion Criteria: Body mass index >40 kg/m². Uncontrolled diabetes mellitus such as hemoglobin A1c (HbA1C) >10% or patients who are not currently treated for their diabetes; Uncontrolled hypertension defined as systolic >160 mmHg or diastolic >100 mmHg (despite hypertensive medication); Proliferative Diabetes Retinopathy (PDR) in the study eye; Evidence of retinal neovascularization. Any previous treatment with focal or grid laser photocoagulation or panretinal photocoagulation (PRP); History of previously treated DME with fluocinolone acetonide implant (Iluvien) injection in the study eye. Visual acuity loss due to an ocular condition that would not improve from resolution of DME (ie, foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition); History of vitreoretinal surgery; Intraocular surgery in the study eye within 4 months of randomization or anticipated over the course of the study; Uncontrolled glaucoma (eg, visual field loss or defined as (IOP) ≥25 mmHg despite treatment with anti-glaucoma medication); Evidence of active infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye /any intraocular inflammation or infection in either eye within 4 months prior to randomization.

Study: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of D-4517.2 After Subcutaneous Administration in Subjects With Neovascular (Wet) Age-related Macular Degeneration (AMD) or Subjects With Diabetic Macular Edema (DME) (Tejas)

Clinicaltrials.gov Identifier: NCT05387837

Sponsor: Ashvattha Therapeutics, Inc.

Purpose: A study to evaluate the safety, tolerability, and pharmacokinetics of D-4517.2 after subcutaneous administration in subjects with neovascular (wet) age-related macular degeneration (AMD) or subjects with diabetic macular edema (DME).

Design: Nonrandomized, parallel assignment, no masking

Number of Patients: 30

Inclusion Criteria: Overall study inclusion criteria for all subjects: willing and able to give informed consent, comply with all study procedures, and be likely to complete the study. Demonstrated response to prior anti-VEGF treatment since diagnosis as defined by one or more of the following: Reduction of subretinal fluid or intraretinal fluid of greater than equal to 30% from initial diagnosis as measured by SD-OCT. Elimination of prior subfoveal fluid from initial diagnosis as measured by SD-OCT. Increase in BCVA of ≥2 lines from initial diagnosis using Snellen scale. Female subjects may be enrolled if they are: Not pregnant, lactating, or breastfeeding. Documented to be surgically sterile or postmenopausal. Female subjects of childbearing potential must practice true abstinence for at least 28 days prior to investigational product (IP) administration until 30 days after the last IP administration and have a negative serum and urine pregnancy test at screening and Baseline day 1, respectively, or using 2 forms of highly effective contraception, including 1 physical barrier (condom or diaphragm) plus another method, such as adequate hormonal method (eg, contraceptive implants, injectables, or oral contraceptives) or nonhormonal methods (eg, intrauterine device or spermicidals) from screening or at least 2 weeks prior to IP administration (whichever is earlier) until 30 days after the last IP administration and having a negative serum and urine pregnancy test at screening and Baseline day 1, respectively. Male subjects with female partners of childbearing potential may be enrolled if they are: Documented to be surgically sterile (vasectomy), or practicing true abstinence for 30 days after the last IP administration, or using 2 adequate forms of highly effective contraception, 1 of which should be a physical barrier for 30 days after the last IP administration. Must agree not to donate sperm during study and for 30 days following administration of the last dose of IP.

Exclusion Criteria: medical conditions: 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 with systolic BP ≥160 mmHg and/or diastolic BP ≥95 mmHg (while patient at rest) at the screening visit. If the patient’s initial reading exceeds these values, a second reading may be taken 30 minutes later on the same day. If the patient’s BP is controlled by antihypertensive medication, the patient should be taking the same medication continuously for at least 30 days prior to day 1. Currently untreated diabetes mellitus or previously untreated subjects who initiated oral or injectable anti-diabetic medication within 3 months prior to day 1. Uncontrolled diabetes mellitus as defined by HbA1c >12%. Chronic renal disease requiring chronic hemodialysis or renal transplantation. Abnormal liver function, as defined by transaminase or total bilirubin 2 times above the upper limit of normal at the screening visit. Medical history of Wolff-Parkinson-White syndrome, family history of long QT, or on medication prolonging QT time or planned initiation during the trial. Known allergy to constituents of the study drug formulation, aflibercept, or clinically relevant hypersensitivity to fluorescein used by the patient during the study. Serious systemic infection: Any active infection for which systemic anti-infectives were used within 4 weeks before randomization. Recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject. Any organic or psychiatric disorder, or laboratory abnormality which, in the opinion of the investigator, will prevent the patient from completing the study activities as in the protocol or interfere with the interpretation of the study results. An underlying condition (including, but not limited to, metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious, or gastrointestinal) or history of other disease, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of study drug, might affect interpretation of the results of the study or which, in the opinion of the investigator, renders the patient at unacceptable risk of treatment complications by participating in the trial. Any major illness or surgical procedure within 1 month before screening. History of other diseases, physical examination finding, historical or current clinical lab finding giving reasonable suspicion of condition that contraindicates the use of the IP or that might affect the interpretation of the results of the study or renders the patient at high risk for treatment complications, in the opinion of the investigator. Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, or HIV type 1 and 2 antibodies. Prior/concomitant therapy: Participation in any investigational study within 30 days prior to screening, or planned use of an IP or device during the study; any exposure to a prior investigational drug product must be fully washed out (at least 5 half-lives). Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable study participant or unlikely to complete the trial. Use of systemic medications known to be toxic to the lens, retina, or optic nerve (eg, deferoxamine, chloroquine/hydroxy-chloroquine, tamoxifen, phenothiazines, and ethambutol) used during the 6 month or 5 half-lives (whichever is longer) prior to day 1 or likely need to be used. Use of systemic immunomodulatory treatments (eg, interleukin-6 inhibitors) within 6 months or 5 half-lives (whichever is longer) prior to day 1. Use of systemic corticosteroids within 1 month prior to day 1. Systemic treatment for suspected or active systemic infection. Administration of systemic anti-VEGF or pro-VEGF treatment within 180 days or 5 half-lives, whichever is longer, before randomization visit. Any prior concomitant systemic anti-VEGF treatment within 6 months or 5 half-lives, whichever is longer, before randomization visit.

Information: bella@attx.com

Study: AG-73305 Single Ascending-dose Cohort Study in DME

Clinicaltrials.gov Identifier: NCT05301751

Sponsor: Allgenesis Biotherapeutics Inc.

Purpose: This is a multicentered, open-labeled, single ascending-dose cohort study to evaluate 4 dosing cohorts of AG-73305 administered by intravitreal injection in patients with diabetic macular edema (DME).

Design: Nonrandomized, sequential assignment, no masking

Number of Patients: 25

Inclusion Criteria: Male or female, 18 years of age or older at the screening visit. Prior diagnosis of diabetes mellitus (Type 1 or Type 2) as defined by World Health Organization or American Diabetes Association. Presence of center-involving DME in the study eye with CST ≥325 μm. Visual acuity loss in the study eye attributed to DME with screening and baseline ETDRS BCVA letter score of 20 to 55 (20/400 to 20/80 Snellen equivalent) in the sentinel patients and 35 to 70 (20/200 to 20/40 Snellen equivalent) in the nonsentinel patients.

Exclusion Criteria: Uncontrolled diabetes mellitus, defined as hemoglobin A1c >12.0% at screening. Uncontrolled hypertension with systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥100 mmHg at screening or Baseline. Chronic renal disease. Any active infection in either eye. Any anti–vascular endothelial growth factor (VEGF) treatment in the study eye within 6 to 8 weeks prior to Baseline. Use of Ozurdex (dexamethasone) within 6 months prior to Baseline or any use of Iluvien (fluocinolone acetonide) in the study eye. Uncontrolled intraocular pressure (IOP), defined as an IOP >25 mmHg, despite anti-glaucoma medications in the study eye at the time of screening or controlled glaucoma that requires management with >2 topical hypotensive medications.

Information: tan.nguyen@allgenesis.com

Study: A Study to investigate RO7200220 in Diabetic Macular Edema

Clinicaltrials.gov Identifier: NCT05151731

Sponsor: Hoffmann-La Roche

Purpose: Study BP43445 is a phase 2, multicenter, randomized, double-masked, active comparator-controlled study to investigate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7200220 administered intravitreally in participants with diabetic macular edema. Only one eye will be chosen as the study eye. The duration of the study will be 52 weeks.

Design: Randomized, parallel assignment, triple masking

Number of Patients: 320

Inclusion Criteria: Diagnosis of diabetes mellitus (Type 1 or Type 2). Macular thickening secondary to diabetic macular edema (DME) involving the center of the macula. Decreased visual acuity attributable primarily to DME. Ability and willingness to provide written informed consent and to comply with the study protocol. Willingness to allow aqueous humor collection. For women of childbearing potential: agreement to remain abstinent or use at least 2 acceptable contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 12 weeks after the final dose of study treatment.

Exclusion Criteria: Hemoglobin A1c (HbA1c) >12%. Uncontrolled blood pressure, defined as a systolic value >180 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. Prior treatment with panretinal photocoagulation or macular laser to the study eye. Any intraocular or periocular corticosteroid treatment within the past 16 weeks prior to day 1 to the study eye. Prior Iluvien or Retisert implants within 3 years prior to day 1 to the study eye. Prior anti-VEGF treatment within the past 8 weeks prior to day 1 to the study eye. Prior administration of IVT brolucizumab in either eye. Any proliferative diabetic retinopathy. 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 Investigate RO7200220 in Combination With Ranibizumab in Diabetic Macular Edema

Clinicaltrials.gov Identifier: NCT05151744

Sponsor: Hoffmann-La Roche

Purpose: Study BP43464 is a phase 2, multicenter, randomized, double-masked active comparator-controlled study designed to assess the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of RO7200220 in combination with anti–vascular endothelial growth factor (VEGF) inhibitor ranibizumab compared with ranibizumab alone in participants with diabetic macular edema. Only one eye will be chosen as the study eye. The duration of the study will be 52 weeks.

Design: Randomized, parallel assignment, triple masking

Number of Patients: 160

Inclusion Criteria: Diagnosis of diabetes mellitus (Type 1 or Type 2). Macular thickening secondary to diabetic macular edema (DME) involving the center of the macula. Decreased visual acuity attributable primarily to DME. Ability and willingness to provide written informed consent and to comply with the study protocol. Willingness to allow aqueous humor collection. For women of childbearing potential: agreement to remain abstinent or use at least 2 acceptable contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 12 weeks after the final dose of study treatment.

Exclusion Criteria: Hemoglobin A1c (HbA1c) >12%. Uncontrolled blood pressure, defined as a systolic value >180 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. Prior treatment with panretinal photocoagulation or macular laser to the study eye. Any intraocular or periocular corticosteroid treatment within the past 16 weeks prior to day 1 to the study eye. Prior Iluvien or Retisert implants within 3 years prior to day 1 to the study eye. Prior anti-VEGF treatment within the past 8 weeks prior to day 1 to the study eye. Prior administration of IVT brolucizumab in either eye. Any proliferative diabetic retinopathy. 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 Investigate Faricimab Treatment Response in Treatment-naïve, Underrepresented Patients With Diabetic Macular Edema

Clinicaltrials.gov Identifier: NCT05224102

Sponsor: Genentech, Inc.

Purpose: This phase 4 study is designed to investigate treatment response in treatment-naïve underrepresented patients with diabetic macular edema (DME) who are treated with faricimab. The study population will consist of participants ≥18 years of age who self-identify as Black/African American, Hispanic/Latino American, or Native American/Alaska Native/Native Hawaiian or other Pacific Islander.

Design: Single group, no masking

Number of Patients: 120

Inclusion Criteria: Ocular inclusion criteria for study eye: intravitreal (IVT) treatment-naïve in the study eye (ie, have not received previous treatment with any anti-VEGF IVT or any corticosteroids periocular or IVT in the study eye). Diabetic macular edema, defined as macular thickening by SD-OCT involving the center of the macula. BCVA letter score of 73 to 20 letters (both inclusive) using the ETDRS protocol at the initial testing distance of 4 meters at the baseline visit (day 1). Clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images to confirm diagnosis.

Exclusion Criteria: Ocular exclusion criteria for study eye: high-risk proliferative diabetic retinopathy (PDR) in the study eye, using any of the following established criteria for high-risk PDR: Any vitreous or preretinal hemorrhage; Neovascularization elsewhere ≥1/2 disc area within an area equivalent to the mydriatic ETDRS 7 fields on clinical examination or on CFPs; Neovascularization at disc ≥1/3 disc area on clinical examination. Tractional retinal detachment, preretinal fibrosis, vitreomacular traction, or epiretinal membrane involving the fovea or disrupting the macular architecture in the study eye, as evaluated by the central reading center. Any history of or ongoing rubeosis iridis. Any panretinal photocoagulation or macular laser (focal, grid, or micropulse) photocoagulation treatment received in the study eye prior day 1. Any history of treatment with anti-VEGF or any periocular or IVT corticosteroids in the study eye prior to day 1. Any treatment for dry eye disease in the last month prior to day 1 (eg, cyclosporine eye drops, lifitegrast eye drops). Lubricating eye drops and ointments are permitted. Any treatment with anti-inflammatory eye drops (eg, doxycycline) within 1 month prior to day 1. Any intraocular surgery (eg, cataract 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. Uncontrolled glaucoma. Any active or suspected ocular or periocular infections on day 1. Any presence of active intraocular inflammation on day 1 (ie, Standardization of Uveitis Nomenclature [SUN] criteria >0 or National Eye Institute [NEI] vitreous haze grading >0) or any history of intraocular inflammation. Any history of idiopathic, infectious, or noninfectious uveitis. Any current ocular condition or other causes of visual impairment for which, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema.

Information: global-roche-genentech-trials@gene.com

Study: Multicenter Study on the Efficacy and Safety of OCS-01 in Subjects With Diabetic Macular Edema

Clinicaltrials.gov Identifier: NCT05066997

Sponsor: Oculis

Purpose: The purpose of this study is to evaluate the efficacy and safety of OCS-01 ophthalmic suspension vs vehicle alone in subjects with DME.

Design: Randomized, parallel assignment, double masking

Number of Patients: 482

Inclusion Criteria: Have a signed informed consent form before any study-specific procedures are performed; Have DME with presence of intraretinal and/or subretinal fluid in the study eye, with central subfield thickness (CST) of ≥310 µm (may be adjusted based on gender specific requirements) by SD-OCT at screening (visit 1) (as assessed by an independent reading center); CST is not part of the eligibility reconfirmation on day 1. Have a documented diagnosis of type 1 or type 2 diabetes mellitus and a glycosylated hemoglobin A1c (HbA1c) of ≤12.0% (≤108 mmol/mol) at visit 1 (screening).

Exclusion Criteria: Have macular edema considered to be because of a cause other than DME.

Information: naleni.eigensatz@oculis.com

Study: Safety, Tolerability, and Evidence of Activity Study of UBX1325 in Patients With Diabetic Macular Edema (DME)

Clinicaltrials.gov Identifier: NCT04857996

Sponsor: Unity Biotechnology, Inc.

Purpose: This study is intended to assess the safety, tolerability, and evidence of pharmacodynamic activity of a single intravitreal (IVT) injection of UBX1325 in patients with diabetic macular edema (DME).

Design: Randomized, parallel assignment, double masking

Number of Patients: 62

Inclusion Criteria: Patients aged ≥8 years. Nonproliferative diabetic retinopathy (DR) patients with DME who had at least 3 anti-VEGF treatments in the preceding 6 months prior to day 1, with the last anti-VEGF given between 3 and 5 weeks prior to day 1. Center-involved DME with central subfield thickness (CST) ≥350 µm on SD-OCT at screening. BCVA in the study eye (most affected) of 70 to 20 ETDRS letters (equivalent to 20/40 to 20/400 on the Snellen chart) at screening and at day 1.

Exclusion Criteria: Concurrent disease in the study eye or structural damage, other than DME, that could compromise BCVA, prevent BCVA improvement, require medical or surgical intervention during the study period, confound interpretation of the results, or interfere with assessment of toxicity or color fundus photography (CFP) in the study eye. 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 condition, including laboratory findings and findings in the medical history or in the prestudy assessments, that, in the opinion of the investigator, constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation or prevent the patient from fully participating in all aspects of the study. Significant media opacities, including cataract, which might interfere with VA, assessment of toxicity, or fundus imaging.

Information: UBX1325_medicalmonitor@unitybiotechnology.com

Study: Study of the Safety and Efficacy of APX3330 in Diabetic Retinopathy (ZETA-1)

Clinicaltrials.gov Identifier: NCT04692688

Sponsor: Ocuphire Pharma, Inc.

Purpose: The objective of this study is to evaluate the safety and efficacy of APX3330 to treat diabetic retinopathy (DR) and diabetic macular edema (DME).

Design: Randomized, parallel assignment, quadruple masking

Number of Patients: 100

Inclusion Criteria: Males or nonpregnant females ≥18 years of age. At least one eye with DR graded at least moderately severe to severe NPDR or mild PDR (corresponding to DRSS 47, 53, or 61). BCVA assessed by ETDRS protocol letters score of ≥60 letters (Snellen equivalent ≥20/63). Body mass index (BMI) between 18 and 40 kg/m², inclusive.

Exclusion Criteria: Ophthalmic: Any prior treatment in the study eye with: Focal or grid laser photocoagulation within the past year or PRP at any time. Systemic or intravitreal anti-VEGF agents within the last 6 months. Intraocular steroids, including triamcinolone and dexamethasone implant, within the last 6 months Fluocinolone implant within the last 3 years. Active uveitis, vitritis, or infection in either eye including infectious conjunctivitis, keratitis, scleritis, or endophthalmitis. Ocular incisional surgery, including cataract surgery, in the study eye within 3 months. Clinically significant ocular disease in either eye. Presence of macular or retinal vascular disease, including diabetic macular edema, retinopathy from causes other than diabetes, age-related macular degeneration, pattern dystrophy, choroidal neovascularization of any cause, retinal vein occlusion, or retinal artery occlusion in the study eye. History of retinal detachment, full-thickness macular hole in the study eye, or idiopathic or autoimmune uveitis in either eye. Systemic: Known hypersensitivity or contraindication to study drug. Any disease or medical condition that in the opinion of the investigator would interfere with the study, prevent the subject from successfully participating in the study, or which might confound the study results. Participation in any investigational study within 30 days prior to screening or planning to participate in any other investigational drug or device clinical trials within 30 days of study completion. Resting HR outside the specified range (50-110 beats per minute). Known to be immunocompromised or receiving immunosuppressive therapy. Hypertension with resting diastolic blood pressure (BP) >105 mmHg or systolic BP >200 mmHg. History of chronic liver disease or presence of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) consistent with such diagnosis. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control.

Information: dcoleman@ocuphire.com

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 2 phase 3 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.

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 2b 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 nonproliferative 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 rescreening for this criterion is permitted. History of other diseases, other nondiabetic 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, nonmelanoma 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 rescreening for this criterion is permitted. Any febrile illness within 1 week prior to day 1. One rescreening 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, or 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. Nonfunctioning 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, multicenter 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), or 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 (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 patient’s 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 µm 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 panretinal 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 (eg, 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 (eg, 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 µm 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 panretinal 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 (eg, 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 (eg, 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 to 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 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. Center-involved DME (CI-DME) with CST of ≥320 µm in men or ≥305 µm 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 center-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 neovascularization at the disc in the study eye. Presence of iris neovascularization 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 hemoglobin 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 noninferior 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 and 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 (eg, 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 (eg, 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 ≥325 µm on Spectralis or 300 µm 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 (eg, anaphylaxis, difficulty breathing) or other reason that the patient is unable to undergo fluorescein angiography (eg, 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 -8.0 D 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-involved 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: The Study of YD312 Tablet in Patients With Diabetic Macular Edema

Clinicaltrials.gov Identifier: NCT03635814

Sponsor: YD Global Life Science Co., Ltd.

Purpose: This phase 2b study’s objective 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.

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 nondiabetic 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: 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: 275 μm in women, and 290 μm in men; Heidelberg Spectralis: 290 μm in women, and 305 μm 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: 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 µm 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

RETINAL VEIN OCCLUSION

NEW: Study: Safety and Proof of Concept Study of ANXV (Annexin A5) in Patients With Retinal Vein Occlusion

Clinicaltrials.gov Identifier: NCT05532735

Sponsor: Annexin Pharmaceuticals AB

Purpose: Randomized, double-masked placebo controlled study to evaluate safety and proof of concept with ascending doses of ANXV (human recombinant Annexin A5 protein) during 5 consecutive days treatment in patients recently diagnosed with retinal vein occlusion.

Design: Randomized, sequential assignment, quadruple masking

Number of Patients: 28

Inclusion Criteria: Must have given written informed consent (signed and dated), and any authorizations required by local law and be able to comply with all study requirements. Male or female, ≥18 years of age at the time of informed consent. Females must be non-pregnant and non-lactating, and either surgically sterile (eg, ≥6 weeks post bilateral salpingectomy, bilateral oophorectomy with or without hysterectomy) or post-menopausal (12 months of spontaneous amenorrhea in females >55years of age or, in females ≤55 years, or 12 months of spontaneous amenorrhea without an alternative medical, or 12 months with an elevated Follicle Stimulating Hormone (FSH) level Males must either be surgically sterile or abstinent*, or if engaged in sexual relations with a female of child-bearing potential, the subject or the subject's non-pregnant female partner must use a highly effective contraception method from the time of signing the Informed Consent Form (ICF) until at least 30 days after the last dose of study drug; Refer to Section 10.3 for acceptable methods. *Abstinence is only acceptable as true abstinence, ie, when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods). Declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception (Section 10.3). Onset of symptoms of Retinal Vein Occlusion within 14 days prior to informed consent. BCVA score of less than 69 letters and greater than 34 letters (approx. 20/40 - 20/200 Snellen equivalent) on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart in the study eye. Clear ocular media and adequate pupillary dilation in the Study Eye to permit high quality retinal imaging Willing to refrain from strenuous exercise/activity (for example heavy lifting, weight training, intense aerobics classes etc.) for at least 72 hours prior to study visits A negative rapid SARS-CoV-2 (COVID) test on Day 1 prior to initiation of study drug infusion.

Exclusion Criteria: Study eye only: a retinal area of non-perfusion (ranp) that is >30 disc areas (DA) on ultra-wide field fluorescein angiography (UWF-FA) confirmed by the CRC. A relative afferent pupillary defect (RAPD). Evidence of deep, extensive intraretinal hemorrhage. Evidence of neovascularization confirmed by the CRC. Ocular disorders/additional eye disease, which in the opinion of the Investigator may confound interpretation of study results, compromise protocol assessments or are likely to require intervention during the study, including, but not limited to, atrophy of the retinal pigment epithelium, sub-retinal fibrosis, organized hard exudate plaque, clinically significant diabetic macular edema, retinal detachment, macular hole, vitreomacular traction, macular epiretinal membrane, clinically significant cataract, vitreal opacities or hemorrhage, glaucoma with documented visual field loss, ischemic optic neuropathy, retinitis pigmentosa or choroidal neovascularization of any cause (eg, age-related macular degeneration (AMD), ocular histoplasmosis, toxoplasmosis, or pathologic myopia). Laser photocoagulation in the study eye within the preceding 6 months prior to the screening visit. Receipt within the past 6 months prior to the screening visit of any intraocular or periocular surgery (including refractive surgery, cataract surgery), or intravitreal (IVT) injection, or planned intraocular surgery or procedure during the study. History of, or current evidence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus). Both eyes: Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens, or optic nerve (eg, desferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol). Known hypersensitivity or allergy to fluorescein (eg, bronchospasm, rash, etc.) or to any component of the study products or a contraindication to dilation of the pupil or fixed pupils; mild allergies without angio-edema or treatment need may be acceptable if deemed not to be of clinical significance (including but not limited to allergy to animals or mild seasonal hay fever). History of glaucoma or an IOP greater than 24 mmHg that is not controlled with medication or surgery at the time of the screening visit. History of, or presence of uveitis, presence of intraocular inflammation (history of blepharitis is not exclusionary), current ocular infection, general. Unwillingness or inability to attend all study visits and/or perform all procedures/tests/examinations, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the investigator. Any medical or surgical procedure or trauma within 4 weeks prior to day 1 (study drug administration), or planned major surgery within the duration of the study through day 43. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study. Prior exposure to a recombinant Annexin A5. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to biologics (for example systemically administered recombinant proteins/peptides; a similar drug class to ANXV). Uncontrolled hypertension (systolic >180 mmHg or diastolic >110 mmHg). Prior or current use of any systemically administered anti-angiogenic agent (eg, bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib) or corticosteroids, approved or investigational. History of malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated. A history of or current systemic infection or inflammation that may require antiviral or antimicrobial therapy that will not be completed prior to Screening Visit, or that in the opinion of the Investigator and with concurrence of the Medical Monitor may either put the subject at risk or may influence the results of the study, or the subject's ability to participate in the study. Treatment with another investigational drug, biological agent, or device within 3 months of Screening Visit, or 5 half-lives of investigational agent, whichever is longer or planned participation in an investigational trial from signing ICF through day 43. History of thromboembolic events or deep venous thrombosis within 6 months of screening visit. Current use of anticoagulant medication (any medications that might have effect on coagulation, hemostasis, and platelets); 81 mg aspirin allowed prior to informed consent but must be stopped at the time of consent; may begin again 1 day post day 5 infusion. Current daily use of benzodiazepines (intermittent use permissible with MM approval). History of significant bleeding (gross hematuria, hemoptysis, gastrointestinal tract bleeding). Evidence or history of a hypercoagulable state (eg shortened APTT). History of autoimmune disease with anticipated presence of persistent Annexin A5 antibodies, eg, antiphospholipid syndrome, systemic lupus erythematosus, rheumatoid arthritis, Behcet disease or systemic sclerosis. Inherited blood disorder (eg sickle cell disease, thalassemia). History of coronary artery disease or cerebrovascular accident within the last 6 months. Estimated Glomerular Filtration Rate (eGFR) (based on plasma-creatinine) outside of normal range at screening or known renal impairment (≤70 mL/min). Recent history of, or current drug or alcohol abuse, current excessive smoking (ie, ≥20/day). Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B. Body mass index ≥30 kg/m² at the time of informed consent.

Information: anna.frostegard@annexinpharma.com

Study: Vascular Endothelial Growth Factor (VEGF) Levels in Retinal Vein Occlusion (RVO) During Anti-VEGF Treatment

Clinicaltrials.gov Identifier: NCT04707625

Sponsor: Wake Forest University Health Sciences

Purpose: The purpose of this study is to treat patients with retinal vein occlusion with standard of care anti–vascular endothelial growth factor therapy and to correlate levels of vascular endothelial growth factor in the anterior chamber fluid of the eye. This study will evaluate if measuring the vascular endothelial growth factor will help predict the timing of when anti–vascular endothelial growth factor therapy will be needed.

Design: Single group, no masking

Number of Patients: 10

Inclusion Criteria: Willingness and ability to provide written informed consent. Diagnosis of Retinal Vein Occlusion with macular edema and central foveal thickness of ≥300 µm confirmed by intravenous fluorescein angiography and Optical Coherence Tomography. Visual Acuity between 20/25 and 5/200.

Exclusion Criteria: Bilateral retinal vein occlusion. Vision worse than 5/200 in study eye. History of myocardial infarction, ischemia, or cerebrovascular accident within 6 weeks of screening. Concurrent Proliferative Diabetic Retinopathy and/or Maculopathy. Concurrent Exudative Age-related Macular Degeneration. Concurrent optic neuropathy with the presence of an afferent pupillary defect. Previous vitrectomy in the study eye. Currently pregnant or planning to become pregnant during the duration of the study. Women currently breastfeeding are also excluded. Previous treatment for retinal vein occlusion in the study eye. Any current medical condition which, in the opinion of the investigator is considered to be uncontrolled. History of allergy or hypersensitivity to study treatment, fluorescein, or any study procedure and treatment related ingredients (eg, topical anesthetics, betadine, etc).

Information: mhnelson@wakehealth.edu

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 (eg, ischemic maculopathy, Irvine-Gass syndrome, foveal atrophy, foveal fibrosis, pigment abnormalities, dense subfoveal hard exudates, or other nonretinal 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 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 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 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 (eg, ischemic maculopathy, Irvine-Gass syndrome, foveal atrophy, foveal fibrosis, pigment abnormalities, dense subfoveal hard exudates, or other nonretinal 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 vitreoretinal 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 µm 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 (eg, 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: 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; coexistent ocular disorder of the cornea, lens, or media that will interfere with assessment of safety or efficacy.

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 nonherpetic 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 retinal detachment. Active retinal or iris neovascularization. Macular edema requiring ongoing 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 (>9.0 D); 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

UVEITIS

Study: A Study of Brepocitinib in Adults With Active Noninfectious Nonanterior Uveitis (NEPTUNE)

Clinicaltrials.gov Identifier: NCT05523765

Sponsor: Priovant Therapeutics, Inc.

Purpose: This study will evaluate the clinical safety and efficacy of oral brepocitinib in participants with active, noninfectious intermediate, posterior, or panuveitis (NIU).

Design: Randomized, parallel assignment, triple masking

Number of Patients: 24

Inclusion Criteria: Adult subjects (18 to 74 years old); diagnosis of noninfectious uveitis (intermediate uveitis, posterior uveitis, or panuveitis); active uveitic disease as defined by the presence of at least 1 of the following parameters in at least 1 eye, as determined by the investigator: Active, inflammatory chorioretinal and/or retinal vascular lesion; or ≥2+ vitreous haze grade (NEI/SUN criteria). Receiving ongoing (or initiated during screening) therapy with oral prednisone. Receiving up to one non-corticosteroid, non-biologic, immunomodulatory therapy. Weight >40 kg with a body mass index <40 kg/m².

Exclusion Criteria: Has isolated anterior uveitis; has confirmed or suspected current diagnosis of infectious uveitis. History of: any lymphoproliferative disorder; active malignancy; history of cancer within 5 years prior to screening (exceptions for basal cell carcinoma, squamous cell carcinoma, ductal carcinoma in situ of the breast, carcinoma in situ of the uterine cervix, or thyroid carcinoma.). At a risk of thrombosis and cardiovascular disease; have a high risk for herpes zoster reactivation; have active or recent infections; other protocol defined inclusion/exclusion criteria may apply.

Information: NeptuneStudyManager@priovanttx.com

Study: Fluocinolone Acetonide Intravitreal Implant 0.18 mg in the Treatment of Chronic Noninfectious Posterior Segment Uveitis

Clinicaltrials.gov Identifier: NCT05322070

Sponsor: Eyepoint Pharmaceuticals, Inc.

Purpose: A study to evaluate the safety and efficacy of Yutiq 0.18 mg intravitreal implant for the management of chronic noninfectious posterior segment uveitis (intraocular inflammation) that has responded to previous steroid therapy.

Design: Single group, no masking

Number of Patients: 125

Inclusion Criteria: Male or female in good general health at least 18 years of age at time of consent; presence of active, recurrent, unilateral or bilateral noninfectious uveitis affecting the posterior segment (intraocular inflammation) with a duration of at least 3 months from initial diagnosis, as determined by the investigator. Intermediate or panuveitis will also be allowed if posterior segment involvement is part of the diagnosis; posterior segment inflammation that has previously demonstrated a clinical response to ≥1 localized corticosteroid treatment (eg, topical steroid 2 to 4 times per day or intra- or periocular injection; presence of macular edema as measured by spectral-domain - optical coherence tomography (SD-OCT) (≥325 µm on Heidelberg SPECTRALIS and ≥315 µm on Zeiss CIRRUS; best-corrected visual acuity (BCVA) of the study eye 35 to 75 letters on the ETDRS chart (Snellen range 20/30 to 20/200); not planning to undergo elective ocular surgery during the study; able to understand, sign the Informed Consent Form (ICF); willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria: History of macular edema due to diabetes, retinal vein occlusion (RVO), age-related macular degeneration (AMD), or any noninflammatory cause; intraocular inflammation with infectious etiology; diagnosis of uncontrolled glaucoma or ocular hypertension at screening, unless study eye is being treated with ≤2 intraocular pressure (IOP)–lowering medications and/or has been previously treated with an incisional surgical procedure or glaucoma laser procedure resulting in stable IOP in the normal range (10 to 21 mmHg); intraocular pressure >21 mmHg or concurrent therapy at screening with >2 IOP-lowering pharmacologic agents in the study eye; ocular malignancy in either eye, including choroidal melanoma; previous viral retinitis; toxoplasmosis scar or scar related to previous viral retinitis in the study eye; ocular and periocular infections such as diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, mycobacterial infections of the eye, or fungal diseases of ocular structures; hypersensitivity to any of the ingredients contained in Yutiq; media opacity precluding evaluation of retina and vitreous (eg, vitreous hemorrhage); any current retinal detachment or retinoschisis in insertion in the study eye; chronic hypotony, defined as <6 mmHg for at least 1 month's duration, and documented on at least 2 separate visits; ocular surgery within 12 weeks prior to day 1; YAG laser capsulotomy within 30 days prior to day 1; Prior intravitreal treatment with Retisert, Iluvien, or Yutiq (0.18 mg) within 36 months prior to day 1; prior intravitreal treatment with Ozurdex within 12 weeks prior to day 1; prior intravitreal treatment with Triesence or Trivaris (triamcinolone) within 12 weeks prior to day 1; periocular or subtenon steroid treatment within 12 weeks prior to day 1; radiation to the head or neck within 2 years prior to screening; steroid allergy, particularly to fluocinolone; any systemic condition that requires chronic systemic anti-inflammatory, steroid, or immunosuppressive therapy (subjects on a stable dose of oral prednisone <7.5 mg per day for a nonocular indication may be included); positive test for human immunodeficiency virus (HIV), tuberculosis, or syphilis in the past 2 years or during screening; any severe acute or chronic medical (eg, cancer diagnosis) or psychiatric condition that could increase the risk associated with study participation or could interfere with the interpretation of study results and make the subject inappropriate for study enrollment; any other systemic or ocular condition which, in the judgment of the investigator, could make the subject inappropriate for study enrollment; treatment with an investigational drug or device within 30 days prior to day 1; pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined in the protocol from at least 14 days prior to day 1 until the final study visit.

Information: tejas.shah@cbcc.global

Study: The Use of 2 YUTIQ vs Sham for Treatment of Chronic Noninfectious Intraocular Inflammation Affecting the Posterior Segment (TYNI)

Clinicaltrials.gov Identifier: NCT05486468

Sponsor: Texas Retina Associates

Purpose: In this study, we aim to compare the recurrence rate of uveitis by month 6 of 2 Yutiq intravitreal implants to sham.

Design: Randomized, parallel assignment, double masking

Number of Patients: 30

Inclusion Criteria: Diagnosed with chronic unilateral or bilateral noninfectious posterior segment inflammation (with or without anterior uveitis) that demonstrated a clinical response to ≥1 previous corticosteroid treatment of any localized type (eg, topical steroid 2 to 4 times per day or intra- or periocular injection) or systemic corticosteroid/immunosuppressant treatment with recurrence following treatment indicating chronicity according to the investigator's judgment. Presence of active posterior segment inflammation as determined by the investigator. Vitreous haze grade ≥2 based on the standardization of uveitis nomenclature (SUN) criteria. Less than 10 anterior chamber cells/high power field determined by slit lamp examination. Not planning to undergo elective ocular surgery during the study.

Exclusion Criteria: History of anterior uveitis only (without associated uveitis that affected the posterior segment). Presence of a vitreous hemorrhage. Uveitis with infectious etiology. Intraocular inflammation associated with a condition other than noninfectious uveitis (eg, intraocular lymphoma). Current infectious diseases of the cornea and conjunctiva, mycobacterial infections of the eye, or fungal diseases of ocular structures. Subjects with anterior chamber intraocular lens (ACIOL) or rupture of the posterior lens capsule. Diagnosis of any form of glaucoma or ocular hypertension at screening, unless the study eye is being treated with ≤2 intraocular pressure (IOP)–lowering medications and/or has been previously treated with an incisional surgical procedure resulting in stable IOP in the normal range (10 to 21 mmHg). Intraocular pressure >21 mmHg or concurrent therapy at screening with >2 IOP-lowering pharmacologic agents in the study eye. Any eye surgery within 12 weeks prior to day 1 of the study. Subjects who are unable to attend scheduled follow-up visits throughout the 12-month study. Has a significant media opacity precluding evaluation of retina and vitreous in the study eye.

Information: tkeesling@texasretina.com

Study: Phase 2b Pivotal Study of Izokibep in Noninfectious Intermediate-, Posterior-, or Pan-uveitis

Clinicaltrials.gov Identifier: NCT05384249

Sponsor: Acelyrin Inc.

Purpose: Izokibep is a small protein molecule that acts as a selective, potent inhibitor of interleukin-17A, to which it binds with high affinity. Izokibep has been investigated in nonclinical and clinical studies including healthy subjects and patients with psoriasis and psoriatic arthritis and is currently being studied in uveitis, axial spondyloarthritis, and hidradenitis suppurativa. This study investigates izokibep in subjects with active noninfectious intermediate-, posterior-, or panuveitis requiring high-dose steroids.

Design: Randomized, parallel assignment, double masking

Number of Patients: 120

Inclusion Criteria: Subject or legally authorized representative has provided signed informed consent including consenting to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Subjects must be 18 to 75 years of age, diagnosed with noninfectious intermediate-, posterior-, or panuveitis. Active disease defined by the presence of at least 1 of the following criteria in at least 1 eye despite treatment with stable doses of corticosteroids for at least 2 weeks prior to day 1: Active, inflammatory, chorioretinal, and/or inflammatory retinal vascular lesion by dilated indirect ophthalmoscopy, fundus photography, fluorescein angiography (FA), and Spectral-Domain Optical Coherence Tomography (SD-OCT) to determine whether a lesion is active or inactive (the central reading center assessment using FA, fundus photography, and/or SD-OCT is required to confirm eligibility prior to day 1). Greater than or equal to 2+ vitreous haze (National Eye Institute [NEI]/Standardization of Uveitis Nomenclature [SUN] criteria) by digital indirect ophthalmoscope and fundus photography (the central reading center assessment using fundus photography is required to confirm eligibility prior to day 1). Currently receiving treatment with oral corticosteroids (≥7.5 mg/day to ≤40 mg/day oral prednisone/prednisolone or corticosteroid equivalent) at a stable dose for at least 2 weeks prior to day 1.

Exclusion Criteria: Disease-related medical conditions: Subject with isolated anterior uveitis. Subject with serpiginous choroidopathy. Subject with confirmed or suspected infectious uveitis. Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the study. Subject with intraocular pressure of ≥25 mmHg while on ≥2 glaucoma medications or evidence of glaucomatous optic nerve injury. Subject with severe vitreous haze that precludes visualization of the fundus prior to first dose of study intervention. Subject has a contraindication for mydriatic eye drops or subject cannot be dilated sufficiently well to permit good fundus visualization. Subject with best-corrected visual acuity (BCVA) <20 letters (Early Treatment Diabetic Retinopathy Study [ETDRS]) in at least 1 eye prior to first dose of study intervention. Subject with proliferative or severe nonproliferative retinopathy or clinically significant macular edema due to diabetic retinopathy. Subject with neovascular/wet age-related macular degeneration. Subject with an abnormality of the vitreo-retinal interface with the potential for macular structural damage independent of the inflammatory process. Subject with a history of active scleritis ≤12 months of first dose of study intervention. Other protocol defined Inclusion/Exclusion criteria may apply.

Information: clinicaltrials@acelyrin.com

Study: A Trial of the Efficacy and Safety of ABY-035 in the Treatment and Prevention of Relapse/Recurrence of Nonanterior Uveitis (LINNAEA)

Clinicaltrials.gov Identifier: NCT04706741

Sponsor: Affibody

Purpose: This is a multinational, multicenter, phase 2 proof-of-concept trial to explore the efficacy and safety of ABY-035 in treating and preventing relapse/recurrence of disease activity in patients with noninfectious intermediate, posterior, or panuveitis with significant BL disease activity despite treatment with stable doses of corticosteroids (≥7 to ≤40 mg/day oral prednisolone or equivalent).

Design: Randomized, parallel assignment

Number of Patients: 110

Inclusion Criteria: Greater than or equal to 18 years of age at SCR. Previously documented medical history with diagnosed unilateral or bilateral NIIPPU. Active disease at BL defined by the presence of at least 1 of the following criteria in at least one eye despite treatment with stable doses of corticosteroids for at least 2 weeks: Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion by Dilated Indirect Ophthalmoscopy (DIO) and Fundus Photography to determine whether a lesion is active or inactive (the central reader's assessment using Fundus Photography is required to confirm eligibility). Greater than or equal to 2+ vitreous haze (NEI/SUN criteria) by DIO and Fundus Photography (the central reader's assessment using Fundus Photography is required to confirm eligibility). On treatment with oral corticosteroids (≥7 to ≤40 mg/day oral prednisolon or equivalent) at a stable dose for at least 2 weeks before BL.

Exclusion Criteria: Subject with isolated anterior uveitis. Subject with Occlusive Behçet's disease, Acute Posterior Multifocal Placoid Pigment Epitheliopathy, Acute Posterior Pigment Epithelitis, Multiple Evanescent White Dot syndrome, Punctate Inner Choroiditis or serpiginous choroidopathy. Subject with confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, syphilis, cytomegalovirus, Lyme disease, toxoplasmosis, Human T-Lymphotropic Virus Type 1 infection, Whipple's disease, herpes zoster virus, and herpes simplex virus. Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial. Planned (elective) eye surgery within 80 weeks after BL. History of prior refractive laser surgery, retinal laser photocoagulation, or neodymium-doped yttrium aluminium garnet posterior capsulotomy within 30 days before BL. History of any other prior ocular surgery within 90 days before BL. Subject with intraocular pressure (IOP) of ≥25 mmHg while on ≥2 glaucoma medications or evidence of glaucomatous optic nerve injury. Subject with severe vitreous haze that precludes visualization of the fundus at BL. Subject has a contraindication for mydriatic eye drops OR subject cannot be dilatated sufficiently well to permit good fundus visualization. Subject with BCVA <20 letters (ETDRS) in at least one eye at BL. Subject with intermediate uveitis or panuveitis who has presence or history of whitish exudates on the inferior pars plana (snowbanking) or vitreal inflammatory aggregates (snowballs) in combination with a medical history or signs or symptoms suggestive of a demyelinating disease such as multiple sclerosis. Subject with proliferative or severe nonproliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy. Subject with neovascular/wet age-related macular degeneration. Subject with an abnormality of the vitreo-retinal interface (ie, vitreomacular traction, epiretinal membranes, etc) with the potential for macular structural damage independent of the inflammatory process. Subject with a history of active scleritis within 12 months of SCR Criteria that relate to comorbidity. Uncontrolled inflammatory bowel disease. Infection requiring treatment with IV anti-infectives within 30 days before BL or oral anti-infectives within 14 days before BL. Subject with any active infection that based on the investigator's clinical assessment makes the subject an unsuitable candidate for the trial. History or any signs of lymphoproliferative disease, or a known malignancy or a history of malignancy within the previous 3 years (except for basal cell or squamous cell carcinoma of the skin that had been fully excised with no evidence of recurrence) Criteria that relate to laboratory testing. A positive test for subclinical/latent TB infection (ie, positive QuantiFERON-TB Gold test or equivalent product) suggestive of TB at SCR will require that the subject is thoroughly evaluated for active tuberculosis. If the subject is diagnosed with latent TB and active TB can be ruled out, the subject can be included if the subject has gone through an adequate course of prophylaxis as per local standard of care 12 weeks prior to SCR. Positive Fluorescent treponemal (FTA)–absorption test (syphilis). Subject with intolerance to high-dose oral corticosteroids (equivalent to oral prednisolone 1 mg/kg/day or 60 mg/day). The subject has received any biologic therapy (including ABY-035 or any other IL-17i or IL-17 receptor inhibitor, eg, secukinumab, ixekizumab, brodalumab, or anti–TNF-α therapy) within 8 weeks before BL. Subject on >1 concomitant nonbiologic NCSIT. Subject on 1 concomitant nonbiologic NCSIT: a) But the medication is not listed as permissible b) The medication is listed as permissible, but the dose has not been stable within the last 3 months before BL c) The medication is listed as permissible, but the dose exceeds the allowable level; to be acceptable, the dose needs to be: i) Methotrexate (MTX) ≤25 mg/week ii) CsA ≤4 mg/kg/day iii) Mycophenolate mofetil ≤2 grams/day or an equivalent drug to mycophenolate mofetil (eg, mycophenolic acid) at an equivalent dose approved by the Medical monitor iv) Azathioprine ≤175 mg/day v) Tacrolimus (oral formulation) ≤8 mg/day. The subject has received Retisert, Iluvien, or Yutiq (glucocorticosteroids implant) within 3 years before BL or who has had complications related to the device. The subject has had any of these glucocorticosteroids implant (glucocorticosteroid implant) removed within 90 days before BL or has had complications related to the removal of the device 29] The subject has received intraocular or periocular corticosteroids within 90 days before BL 30] The subject has received Ozurdex (dexamethasone implant) within 6 months before BL 31] The subject has received intravitreal methotrexate within 90 days before BL 32] The subject has received intravitreal anti- Vascular Endothelial Growth Factor (VEGF) therapy: within 45 days of BL for Lucentis (ranibizumab) or Avastin (bevacizumab). or within 60 days of BL for anti-VEGF Trap (aflibercept). or within 84 days of BL for Beovu (brolucizumab) 33] Subject on systemic carbonic anhydrase inhibitor within 1 week before SCR 34] Subject on cyclophosphamide within 30 days before BL 35] Prior or current use of chlorambucil.

Information: linnaea@affibody.se

Study: Safety and Efficacy of an Injectable Fluocinolone Acetonide Intravitreal Insert (FAI)

Clinicaltrials.gov Identifier: NCT05070728

Sponsor: EyePoint Pharmaceuticals, Inc.

Purpose: A study to evaluate the safety and efficacy of an FAI insert for the management of subjects with noninfectious uveitis affecting the posterior segment of the eye.

Design: Randomized, parallel assignment, double masking

Number of Patients: 60

Inclusion Criteria: Male or non-pregnant female at least 18 years of age at time of consent. One or both eyes having a history of recurrent noninfectious uveitis affecting the posterior segment of the eye (intermediate, posterior, or panuveitis) with or without anterior uveitis >1 year duration. During the 52 weeks prior to enrollment (day 1), the study eye has either received treatment systemic corticosteroid or other systemic therapies given for at least 12 weeks, and/or at least 2 intra- or periocular injections of corticosteroid for management of uveitis OR the study eye has experienced recurrence recurrences of uveitis at least 2 separate times requiring systemic, intraocular or periocular injection of corticosteroid. Subject is not planning to undergo elective ocular surgery during the study. Subject has ability to understand and sign the Informed Consent Form (ICF). Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Other protocol-specified inclusion criteria may apply.

Exclusion Criteria: History of posterior uveitis only that is not accompanied by vitritis or macular edema. History of iritis only associated with no vitreous cells, anterior chamber cells, or vitreous haze at day 1. Uveitis with infectious etiology. Vitreous hemorrhage. Intraocular inflammation associated with a condition other than noninfectious uveitis (eg, intraocular lymphoma). Uveitis limited to the anterior segment, ie, anterior uveitis only. Ocular malignancy in either eye, including choroidal melanoma. Previous viral retinitis. Requirement for chronic systemic or inhaled corticosteroid therapy (>15 mg prednisone daily) or chronic systemic immunosuppressive therapy. History of certain skin cancers (specifically, basal cell carcinoma and squamous cell carcinoma), any malignancy receiving treatment, or in remission less than 5 years prior to day 1. Positive test for human immunodeficiency virus (HIV) or syphilis during screening. Mycobacterial uveitis or chorioretinal changes of either eye which, in the opinion of the investigator, result from infectious mycobacterial uveitis. Systemic infection within 30 days prior to day 1. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined in the protocol from at least 14 days prior to day 1 until the 52-week visit. Other protocol-specified exclusion criteria may apply.

Information: dpaggiarino@eyepointpharma.com

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 (ie 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: Tofacitinib for Inflammatory Eye Disease

Clinicaltrials.gov Identifier: NCT03580343

Sponsor: Washington University School of Medicine

Purpose: Noninfectious 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 10 mg 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 a multicenter randomized, parallel-treatment, comparative effectiveness trial comparing adalimumab to conventional (small molecule) immunosuppression for corticosteroid spring in the treatment of noninfectious, 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) noninfectious, 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-α 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: 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 of the study drug, sirolimus, administered intravitreally in patients with uveitis.

Design: Randomized, parallel assignment, no masking

Number of Patients: 30

Inclusion Criteria: Greater than 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 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