Removed Since Last Issue
• Study: FOCUS: First-in-Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects With Dry AMD
Clinicaltrials.gov Identifier: NCT03846193
Status: Terminated
• 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
Status: Completed
• Study: Safety, Tolerability, and Efficacy Study of UBX1325 in Patients With Neovascular Age-related Macular Degeneration (ENVISION)
Clinicaltrials.gov Identifier: NCT05275205
Status: Completed
• 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
Status: Completed
• Study: A Study to Evaluate THR-149 Treatment for Diabetic Macular Oedema (KALAHARI)
Clinicaltrials.gov Identifier: NCT04527107
Status: Completed
CURRENT CLINICAL TRIALS
DRY AMD
Study: Study to Assess the Safety and Efficacy of OCU410 for Geographic Atrophy
Clinicaltrials.gov Identifier: NCT06018558
Sponsor: Ocugen
Purpose: This is a phase 1/2 study to assess the safety and efficacy of OCU410 for geographic atrophy secondary to dry age-related macular degeneration (AMD).
Design: Randomized, sequential assignment, single masking
Number of Patients: 63
Inclusion Criteria: Subjects 50 years of age or older. BCVA of approximately 24 letters or more using Early Treatment Diabetic Retinopathy Study (ETDRS) chart (20/320 Snellen equivalent). Fundus autofluorescence (FAF) imaging shows: total GA area ≥2.5 and ≤17.5 mm2 (1 and 7 disk areas [DA], respectively); if GA is multifocal, at least one focal lesion must be ≥1.25 mm2 (0.5 DA), with the overall aggregate area of GA; the entire GA lesion must be completely visualized on the macula-centered image and must be able to be imaged in its entirety, and not contiguous with any areas of peripapillary atrophy; absence of any pattern of hyper-autofluorescence in the junctional zone of GA.
Exclusion Criteria: Previous treatment with a gene-therapy or cell therapy product. Previous treatment with any investigational drug or device within 1 year. The history of any investigational product with a washout period of up to 6 months will be evaluated on a case-by-case basis. Previous treatment with Syfovre (Pegcetacoplan injection). GA due to causes other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like Plaquenil maculopathy. however, benign conditions of the vitreous or peripheral retina are not exclusionary (ie, pavingstone degeneration).
Information: umair.qazi@ocugen.com
Study: Study to Evaluate the Efficacy and Safety of Oral CT1812 in Participants With Geographic Atrophy (GA) Secondary to Dry Age-Related Macular Degeneration (AMD)
Clinicaltrials.gov Identifier: NCT05893537
Sponsor: Cognition Therapeutics
Purpose: This is a Phase 2, prospective, multicenter, randomized, double-masked, placebo-controlled 104-week study to assess the efficacy, safety, and tolerability of orally delivered CT1812 compared to placebo in participants with GA associated with dry AMD.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 246
Inclusion Criteria: Age ≥50 years at time of informed consent. BCVA of 24 letters or better using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Stable pharmacological treatment of any other chronic conditions for at least 30 days prior to screening.
Exclusion Criteria: GA due to causes other than dry AMD. Any history or current evidence of exudative ("wet") AMD. Retinal disease other than dry AMD. Any ophthalmologic condition that prevents adequate imaging of the retina as judged by the study site or central reading center. Intraocular surgery (including intraocular lens implantation surgery) within 3 months prior to randomization. Any ophthalmic condition that will or is likely to require surgery during the study period. Hypersensitivity to fluorescein. Suspected or known allergy to any components of the study treatments. History of vitrectomy surgery, submacular surgery or any other surgical intervention for dry AMD. History of glaucoma filtering surgery or corneal transplant in the study eye. History of central serous retinopathy in either eye.
Information: clinicaltrials@cogrx.com
Study: A Multiple Dose Study of AVD-104 for Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD) (SIGLEC)
Clinicaltrials.gov Identifier: NCT05839041
Sponsor: Aviceda Therapeutics, Inc.
Purpose: Investigate the safety, pharmacokinetics, and treatment effects of single and multi-dose of intravitreal AVD-104 in participants with geographic atrophy secondary to age-related macular degeneration.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 210
Inclusion Criteria: Part 1: BCVA in the study eye using ETDRS Chart Visual Acuity Scale (VAS) of 5 to 55 letters (equivalent to Snellen VA of approximately 20/800 - 20/80). If GA is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA). GA may be center involved. Part 2: BCVA in the study eye using ETDRS chart VAS of 24 letters or better (equivalent to Snellen VA of 20/320 or better). Confirmed diagnosis of AMD that is noncenter involving (ie, nonsubfoveal) GA. GA can be multifocal, and cumulative GA lesion must reside completely within the fundus autofluorescence (FAF) imaging field (field 2, 30-degree image centered on the fovea), as confirmed by the central reading center. Total GA area must be ≥ 2.5 and ≤ 15.5 mm2 (1 and 7 disk areas [DA], respectively). If GA is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA), with the overall aggregate area of GA as specified in 4 above. Presence of any pattern of hyper-autofluorescence in the junctional zone of GA. The entire GA lesion must be completely visualized on the macula centered image and must be able to be imaged in its entirety and not contiguous with any areas of peripapillary atrophy.
Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Part 1 and 2: Presence of the following ocular conditions - in the study eye: Exudative AMD or choroidal neovascularization (CNV), including any evidence of retinal pigment epithelium rips or evidence of neovascularization anywhere based on spectral domain optical coherence tomography (SD-OCT) imaging and/or fluorescein angiography as assessed by the Reading Center. Any active ocular disease or condition that in the opinion of the Investigator could confound visual function or the assessment of the macula or be a contraindication to intravitreal (IVT) injection, eg, macular hole, epiretinal membrane, macular atrophy or maculopathies due to any disease other than AMD (such as Stargardt disease, cone rod dystrophy or toxic maculopathies like plaquenil maculopathy), uveitis, uncontrolled glaucoma, or ocular infection (diabetes mellitus without retinopathy is not a criterion for exclusion). Any intraocular surgery (except for intraocular lens replacement surgery more than 3 months prior to consent). Any ophthalmologic condition that reduces the clarity of the media and that, in the opinion of the Investigator, interferes with ophthalmologic examination. Any ocular condition other than GA secondary to AMD that may require surgery or medical intervention during the study period or, in the opinion of the Investigator, could compromise visual function during the study period.
Information: dcallanan@avicedarx.com, marchitto@avicedarx.com
Study: 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: 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: 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
WET AMD
NEW: Study: Safety and Tolerability of KH631 Gene Therapy in Participants With Neovascular Age-related Macular Degeneration
Clinicaltrials.gov Identifier: NCT05657301
Sponsor: Chengdu Origen Biotechnology Co., Ltd.
Purpose: VAN-2201 is Phase I clinical trial to assess the safety and tolerability of KH631 in subjects with neovascular AMD. KH631 is gene therapy designed to deliver a protein which targets and blocks VEGF via an adeno-associated viral vector. The standard of care for patients with neovascular AMD are anti-VEGF treatments, which have demonstrated improvement in vision and reduction in fluid. A one-time placement of a product which inhibits VEGF has the potential to reduce the patient burden of regular intraocular injections.
Design: Single group, no masking
Number of Patients: 25
Inclusion Criteria: Males and females ages 50 to 85 (inclusive) with a study eye which meets the following criteria: Previously received IVT treatment of anti-VEGF for neovascular AMD, with documented response to anti-VEGF therapy during the first 2 weeks of screening; active macular CNV lesion secondary to AMD evidenced by SD-OCT; Have a ETDRS BCVA letter score of 63 to 19 (approximately 20/63 to 20/400 Snellen equivalent) in the study eye at Screening for the first subject in each cohort (sentinel subject), followed by ETDRS BCVA letter score of 73 to 19 (approximately 20/40 to 20/400 Snellen equivalent) for the rest of the subjects each cohort; Pseudophakia in the study eye, with ocular media to permit high quality fundus imaging at screening and allow planned vitrectomy and subretinal injection; Are willing and able to sign the study written informed consent form (ICF).
Exclusion Criteria: Have had any prior ocular or systemic treatment (investigational or approved) or surgery for the treatment of neovascular AMD except IVT anti-VEGF. Retinal pigment epithelial tears or rips at screening. Any history or presence of vitreous hemorrhage; Have any condition preventing visual acuity improvement; Have any other cause of CNV; prior pars plana vitrectomy or scleral buckling or retinal detachment surgery; macular hole, Epiretinal membrane or vitreo-macular traction; full thickness macular hole; History of intraocular or periocular surgery in the prior 3 months; Prior trabeculectomy or other filtration surgery; Any use of long-acting intraocular steroids, including implants, within six months prior.
Information: van2201@cnkh.com
NEW: Study: Study to Evaluate the Safety of CG-P5 Peptide Eye Drops in Patients Diagnosed With Age-related Wet Macular Degeneration
Clinicaltrials.gov Identifier: NCT06132035
Sponsor: Caregen Co. Ltd.
Purpose: This will be a randomized, comparative, parallel, clinical study to assess initial safety and tolerability of CG-P5 peptide eye drops compared to placebo in patients diagnosed with age-related wet macular degeneration.
Design: Randomized, parallel assignment
Number of Patients: 45
Inclusion Criteria: Male or female patients ≥50 years of age. Willing and able to provide written informed consent. Diagnosis of age-related wet macular degeneration (wAMD) in the study eye as determined by the investigator on fundus examination. Primary or recurrent active choroidal neovascularization (CNV) lesions involving the foveal center secondary to age-related wet macular degeneration in any one of the eyes. (If both eyes are affected and eligible, the eye with the worse BCVA, as assessed at screening, will be selected as the study eye. Best corrected visual acuity (BCVA) of 75-25 eye Early Treatment of Diabetic Retinopathy Study (ETDRS) letters (approximate Snellen equivalent between 20/ 32 to 20/320) inclusive before pupil dilation assessed at the initial testing distance of 4 meters. Central Subfield Thickness (CST thickness) ≥250 microns on SD-OCT (exclusive of subretinal pigment epithelial fluid, inclusive of SRF). Presence of SRF and/or IRF on SD-OCT. Total lesion size not greater than 12 disc areas (30.48 mm2) (1 disc area = 2.54 mm2) on FA. If present, subretinal hemorrhage must comprise < 50% of the total lesion area on FA, SD-OCT, or FAF. No subfoveal fibrosis or atrophy on FA, SD-OCT, or FAF. Active CNV membranes with subfoveal leakage or juxtafoveal leakage too close for laser photocoagulation. Females who are of non-childbearing potential (surgically sterile or menopausal) OR if of childbearing potential using effective birth control and non-pregnant & non-lactating. Ability to follow protocol requirements.
Exclusion Criteria: Patients having additional eye disease in the posterior segment of study eye other than wAMD. Any other pathology involving the CNV lesion like retro foveolar atrophy or permanent structural damage to fovea or fibrosis/ hemorrhage involving fovea > 50 % of lesion area of study eye that can affect the efficacy of drug. Vitreous hemorrhage or history of rhegmatogenous retinal detachment, retinal pigment epithelial tear involving the macula or macular hole (stage 3 or 4) in the study eye. Aphakia or absence of the posterior capsule in the study eye. History or expectation of the following surgery in the study eye: Vitrectomy within last 1 month. Cataract surgery or Lasik within the last 3 months. Planned cataract removal surgery during the study. A history or medical diagnosis of uncontrolled glaucoma (defined as IOP >25mmHg even with anti-glaucoma medication), advanced glaucoma resulting in a cup/disc ratio >0.8 in the study eye, or glaucoma filtration surgery in the study eye. Serious complications following surgery in the study eye within 1 year. Current or planned use of medications known to be toxic to the retina, lens, or optic nerve (eg, deferoxamine, chloroquine/hydro chloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol). Medical history or condition: Uncontrolled diabetes mellitus, with glycosylated hemoglobin (HbA1c) >10%, myocardial infarction or stroke within 12 months of screening, active bleeding disorder, major surgery within 1 month of screening or when planned within the study period, hepatic impairment, uncontrolled hypertension, other unstable or progressive cardiovascular, pulmonary, Parkinson, liver, or renal disease or cancer or dementia. Previous treatment with intravenous bevacizumab or intravitreal ranibizumab, bevacizumab, aflibercept, pegaptanib in either of the eyes within four months prior to enrolment. Previous treatment with verteporfin photodynamic therapy (PDT), thermal laser, transpupillary thermotherapy, intravitreal or protein kinase C inhibitors or other AMD therapy in the study eye within 3 months prior to randomization. Previous treatment with intravitreal ocular or periocular steroids (eg, triamcinolone, anecortave acetate) or peribulbar steroid in the study eye within past 3 months. Concurrent use of systemic anti-VEGF agents. Any ophthalmic device implantation within the previous 12 months. Patients with a clinically significant abnormal screening hematology, blood chemistry, or urinalysis, unsuitable for study participation in the investigator's opinion. Aspartate Transaminase (AST), Alanine Transaminase (ALT), alkaline phosphatase, Gamma-glutamyl Transferase (GGT), total bilirubin, direct bilirubin, indirect bilirubin, and LDH ≥ 2.0-fold the upper limit of normal at screening. Patient with impaired renal function defined as calculated creatinine clearance (CLCr) <30mL/min. Males: CLCr = [140 - a(years)] x weight(kg)/72 x serum creatinine (mg/dL). Females: CLCr = [140 - a(years)] x weight(kg) (x 0.85)/72 x serum creatinine (mg/dL). Significant alcohol or drug abuse within past 2 years per investigator judgement. Previous participation in other trials for treatment of wAMD with systemic administration if washout period from last administration is shorter than 3 months. Significant disease or other medical conditions (as determined by medical history, examination, and clinical investigations at screening) that may, in the opinion of the investigator result in the any of the following: Put the patient at risk because of participation in the study, Influence the results of the study, Cause concern regarding the patient's ability to participate in the study. Known hypersensitivity to fluorescein or any of the ingredients used in the study drug formulation, or any of the medications used during the study. Active infectious conjunctivitis in either eye. Women of childbearing potential who are lactating or who are pregnant as determined by serum pregnancy test at screening. Women of childbearing potential must have agreed to use adequate birth control methods for the duration of the study. Postmenopausal women should have documented last MC 2 years before study participation.
Information: ishita.trivedi@cbcc.global
NEW: Study: Study of AR-14034 in Participants With Neovascular Age-Related Macular Degeneration (nAMD) (NOVA-1)
Clinicaltrials.gov Identifier: NCT05769153
Sponsor: Aerie Pharmaceuticals
Purpose: The primary purpose of this study is to evaluate the safety and durability of single- and repeat administration of AR-14034 Sustained Release (SR) in subjects with neovascular age-related macular degeneration (nAMD).
Design: Randomized, parallel assignment
Number of Patients: 140
Inclusion Criteria: Key Inclusion Criteria [Stage 1 and Stage 2]: Presence of an active choroidal neovascularization (CNV) lesion secondary to age-related macular degeneration (AMD); Best corrected visual acuity (BCVA) between 80 and 35 letters (20/25 to 20/200 Snellen equivalent) in the study eye; BCVA greater than 34 letters (approximately 20/200 Snellen equivalent) in the non-study eye; Media clarity and pupillary dilation in the study eye sufficient for all planned study procedures; Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol; Other protocol-specified inclusion criteria may apply.
Exclusion Criteria: History or current ocular disease in the study eye other than nAMD, that, might require medical or surgical intervention during the study; Structural damage to the macula that is likely to preclude improvement in visual acuity in the study eye after resolution of the nAMD; Any active intraocular or periocular infection or active intraocular inflammation; Treatment with ocular anti-VEGF product within 28-days before Week -1 [Stage 1] or Baseline [Stage 2]; Uncontrolled glaucoma in the study eye; Uncontrolled blood pressure; Females of child-bearing potential who are pregnant, intending to become pregnant, nursing, or who are not willing to use an acceptable form of contraception for the duration of the study; Other protocol-specified exclusion criteria may apply.
Information: alcon.medinfo@alcon.com
NEW: Study: A Phase 2 Study to Assess the Efficacy and Safety of KHK4951 in Patients With Neovascular Age-Related Macular Degeneration
Clinicaltrials.gov Identifier: NCT06116890
Sponsor: Kyowa Kirin, Inc.
Purpose: The purpose of this study is to evaluate efficacy and safety of KHK4951 eye drops in patients with nAMD.
Design: Randomized, parallel assignment
Number of Patients: 180
Inclusion Criteria: Voluntary written informed consent to participate in the study. Active subfoveal MNV (any subtype) or juxtafoveal MNV secondary to AMD with leakage affecting the fovea in the study eye at screening. BCVA ETDRS letter score of 73 letters to 35 letters in the study eye as measured by the ETDRS visual acuity chart at screening. CST ≥350 μm and ≤450 μm at screening.
Exclusion Criteria: Subretinal hemorrhage, fibrosis, or atrophy of >50% of the total lesion area and/or that involves the fovea in the study eye. Uncontrolled glaucoma in the study eye. Aphakia or pseudophakia with AC-IOL in the study eye. Active intraocular inflammation in the study eye. Any current ocular condition for which visual acuity loss would not improve from resolution of macular edema in the study eye. History of rhegmatogenous retinal detachment in the study eye. Any current or history of ocular disease other than nAMD in the study eye that may confound assessment of the macula or affect central vision. History of the following therapies in the study eye: History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD. Prior treatment PDT with Visudyne, external-beam radiation therapy, transpupillary thermotherapy, or panretinal photocoagulation. Previous use of periocular or intraocular (sub-Tenon or IVT) corticosteroids. Previous intraocular device implantation except PC-IOL. Previous laser (any type) to the macular area. Previous treatment with any IVT anti-VEGF drugs. Any current or history of endophthalmitis in either eye. History of idiopathic or autoimmune-associated uveitis in either eye. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
Information: teppei.kurosawa.gx@kyowakirin.com
Study: Phase I/II Study to Evaluate the Safety, Preliminary Efficacy, Immunogenicity, and Pharmacokinetics of SKG0106 Intraocular Solution in Patients With Neovascular Age-related Macular Degeneration (nAMD)
Clinicaltrials.gov Identifier: NCT05986864
Sponsor: Skyline Therapeutics (US) Inc.
Purpose: This is a phase 1/2 clinical study to evaluate the safety, preliminary efficacy, immunogenicity, and pharmacokinetic (PK) characteristics of SKG0106 in subjects with nAMD. Based on results from the phase 1 dose escalation study, the phase 2 expansion study will be conducted.
Design: Nonrandomized, single group, no masking
Number of Patients: 68
Inclusion Criteria: Voluntary and able to sign a dated ICF prior to any study-related procedures and able to complete the study as required by the protocol; Aged ≥ 50 years at screening; Study Eye: Diagnosis of nAMD as determined by the PI; Active CNV lesions secondary to age-related macular degeneration (AMD); Total CNV area (classical and occult) at screening must account for more than 50% of the total lesion area in the study eye (confirmed by CRC at Phase 2 clinical study); Intraretinal and/or subretinal fluid in the fovea of the retina in the study eye, confirmed by CRC at Phase 2 clinical study; BCVA between 63 and 19 letters (inclusive) in the study eye examined using the Early Treatment of Diabetic Retinopathy Study testing at screening and baseline.
Exclusion Criteria: Any active intraocular or periocular infection or active intraocular inflammation (eg, infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in the study eye at baseline; Results of colorful fundus photography assessment at screening showed fibrotic or geographic atrophic changes in the fovea of retina in the study eye, confirmed by CRC at Phase 2 clinical study; Retinal pigment epithelial tear in the study eye at screening; Current vitreous hemorrhage in the study eye or history of vitreous hemorrhage within 4 weeks prior to baseline; Any condition that, in the opinion of the investigator, may limit visual acuity improvement in the study eye (e.g., history of intraocular disease other than nAMD in the study eye or current evidence of intraocular disease [including retinopathy] that, in the judgment of the investigator, may require medical or surgical intervention to prevent or treat visual acuity lost possibly caused by the condition or may limit the possibility of increased visual acuity following study treatment); History of retinal detachment or active retinal detachment in the study eye; Any prior gene therapy.
Information: yongqin.wang@skytx.com
Study: A Study of EXG102-031 in Patients With wAMD (Everest)
Clinicaltrials.gov Identifier: NCT05903794
Sponsor: Exegenesis Bio
Purpose: In neovascular (wet) age-related macular degeneration (nAMD), the macula, or the part of the eye that provides the clear, detailed central vision, is being affected by abnormal blood vessel growth and leakage. This leakage affects the vision over time and can lead to severe blurriness or blinding. EXG102-031 was made to block the extra vessel formation which would lead to less leakage affecting the vision. Before EXG102-031 can be tested for its efficacy (if it makes vision better), it must be tested to see if it is safely tolerated to confirm it can continue to be studied in more patients with nAMD.
Design: Sequential assignment, no masking
Number of Patients: 6
Inclusion Criteria: Male or female, age ≥50 years of age; diagnosis of nAMD and current active lesion in the study eye at screening; an ETDRS BCVA letter scores between 73 and 19 letters in the study eye; response to anti-VEGF treatment during screening; the study eye must be a pseudophakic lens (postcataract surgery status); and voluntarily agree to participate in the clinical trial, understand the trial procedures, and be capable of signing the informed consent form before screening.
Exclusion Criteria: Presence of any ocular disease or history of disease in the study eye other than nAMD that may affect central visual acuity and/or macular detection, including retinal detachment, or in the opinion of the investigator could limit VA improvement in the study eye; presence in the study eye of CNV or macular edema due to causes other than AMD; presence in the study eye of scarring, fibrosis or atrophy involving the macula; subretinal hemorrhage accumulating in the center of the macula of the test eye, with an area of hemorrhage ≥4 optic disc diameters; active ocular infection in either eye; presence of advanced glaucoma or uncontrolled glaucoma in the study eye; history of intraocular surgery in the study eye within 90 days of screening; or prior receipt of any ocular or systemic gene therapy agent.
Information: quality-exg102-031@exegenesisbio.com
Study: Safety and Tolerability of OCU-10-C-110 for Injection in Subjects With Neovascular Age-related Macular Degeneration
Clinicaltrials.gov Identifier: NCT05904691
Sponsor: Ocugenix Corporation
Purpose: Multicenter, open-label, two-part safety assessment following administration of single ascending doses and repeat administration of the HTD of OCU-10-C-110 for injection in the study eye of participants with nAMD.
Design: Nonrandomized, single group, no masking
Number of Patients: 19
Inclusion Criteria: Angiographically documented active choroidal neovascular (CNV) lesion (ie, leakage on fluorescein angiography or subretinal, intraretinal, or sub-retinal pigment epithelium [sub-RPE] fluid on spectral domain optical coherence tomography [SD-OCT]) secondary to age-related macular degeneration (AMD), within the previous 10 weeks. Subjects must have received, 7 to 14 days prior to the Baseline Visit, an intravitreal injection in the study eye of an anti-vascular endothelial growth factor (VEGF) ocular therapeutic approved for use in the United States.
Exclusion Criteria: History or current evidence of a medical condition (systemic or ophthalmic disease, metabolic dysfunction, physical examination finding or clinical laboratory finding) that may, in the opinion of the investigator, preclude the safe administration of the study medication, adherence to the scheduled study visits, or safe participation in the study or affect the results of the study (eg, unstable or progressive cardiovascular, cerebral vascular, pulmonary, Parkinson's, liver or renal disease, depression, cancer, or dementia). History or evidence of the following surgeries/procedures in the study eye: submacular surgery, vitrectomy, retinal detachment or retinal tear, incisional glaucoma surgery.
Information: sean@ocugenixtx.com
Study: A 2-part Study Consisting of Multiple Ascending Dose (MAD) Safety Study, and a Dose-finding Masked Study to Assess the Safety and Efficacy of Intravitreal (IVT) EYE103 in Patients With Diabetic Macular Edema (DME) or Neovascular Age-related Macular Degeneration (NVAMD) (AMARONE)
Clinicaltrials.gov Identifier: NCT05919693
Sponsor: EyeBiotech Ltd.
Purpose: EYE103-101 is a 2-part study assessing safety and preliminary efficacy of EYE103 in patients with diabetic macular edema (DME) given as monotherapy or neovascular macular degeneration (NVAMD) given in combination with anti-VEGF.
Design: Randomized, sequential assignment, triple masking
Number of Patients: 92
Inclusion Criteria: Be willing and able to understand the study procedures and the risks involved and provide written informed consent before the first study-related activity. DME patients must be ≥18 years of age, NVAMD patients must be ≥50 years of age. Diagnosis of either DME or NVAMD. DME patients must be treatment naïve. NVAMD patients can be either treatment naïve or treatment experienced. DME patients must have vision loss in the study eye. NVAMD patients can be either treatment-naïve or treatment experienced with vision loss in the study eye.
Exclusion Criteria: Be pregnant or breastfeeding. History of cataract surgery and/or minimally invasive glaucoma surgery (MIGS) within 3 months of screening. Yttrium-Aluminum Garnet (YAG) laser capsulotomy within 2 months of screening. Any other condition except for DME or NVAMD or that could affect interpretation of study assessments.
Information: ClinicalInquiries@eyebiotech.com
Study: A Phase 3 Study to Compare the Efficacy and Safety of HLX04-O With Ranibizumab in Subjects With wAMD
Clinicaltrials.gov Identifier: NCT04740671
Sponsor: Shanghai Henlius Biotech
Purpose: This study will compare the efficacy and safety of HLX04-O administered by intravitreal injection (IVT) with ranibizumab in patients with active wAMD.
Design: Randomized, parallel assignment, double masked
Number of Patients: 388
Inclusion Criteria: Capable to understand and sign the informed consent form (ICF) which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Women or men aged ≥50 years when signing the ICF. In the Investigator's judgment, willing and able to complete all visits and assessments adhering to the prohibitions and restrictions specified in this protocol. Newly diagnosed, untreated, active CNV lesions secondary to age-related macular degeneration that affect the central subfield (CSF) in the study eye. Active CNV was defined as leakage on fluorescein angiography (FA) and subretinal or intraretinal fluid on optical coherence tomography (OCT) with confirmation of the reading center during screening. The total lesion area (including hemorrhage, scar and neovascularization) of the study eye ≤12 disc area (DA) with confirmation of the reading center before randomization. The BCVA letters between 24 and 73, inclusive, in the study eye, using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Participants' fellow (non-study) eye must have a BCVA of 24 letters or better. Clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm the diagnosis.
Exclusion criteria: Macular-related retinal pigment epithelial tears in the study eye; scar, fibrosis or atrophy involving the fovea, or CNV due to other causes in the study eye (eg, ocular histoplasmosis, trauma,pathological myopia, etc.) with confirmation of the reading center. The fellow (non-study) eye needs anti-VEGF IVT injection (eg CNV due to wAMD, trauma, pathological myopia, retina vein occlusion, diabetic macular edema, etc.) in the next 3 months after randomization, in the investigator's judgment. Aphakia (except intraocular lens) or posterior capsular rupture of the lens (except yttrium-aluminium-garnet (YAG) laser posterior capsulotomy after intraocular lens implantation ≥30 days prior to first dose) in the study eye. Active or recent (within 1 month prior to dose 1) intraocular, extraocular or periocular infection (including conjunctivitis, keratitis, scleritis or endophthalmitis), or history of idiopathic or autoimmune-associated uveitis in either eye. Vitreous hemorrhage in the study eye within 3 months prior to dose 1. Corneal dystrophy or history of corneal transplantation, scleral softening or history of scleral softening, history of rhegmatogenous retinal detachment or macular hole (Stage II, III or IV) in the study eye. Uncontrolled glaucoma in the study eye (defined as intraocular pressure [IOP] ≥25 mmHg despite treatment with antiglaucoma medication), and/or glaucoma filtering surgery (eg, trabeculectomy, scleral nipping, non-penetrating trabeculectomy, etc.). Equivalent spherical diopter of the study eye ≥-8D. For participants who had undergone refractive correction or cataract surgery, the equivalent spherical diopter of the study eye before surgery ≥-8D. Estimated by the Investigator, any concurrent intraocular condition except wAMD (eg, diabetic retinopathy, dry AMD, retina vein occlusion, uveitis, angioid streaks, retinal detachment, epiretinal membrane, amblyopia, central serous chorioretinopathy, etc.) in the study eye that limited the potential to gain visual acuity upon treatment with the investigational product, or could have required medical or surgical intervention during the study to prevent or treat visual loss. Underwent intraocular surgery including verteporfin photodynamic therapy (PDT), transpupillary thermotherapy, macular translocation, vitrectomy, laser photocoagulation in macular area, other surgery in macular area or surgery to treat AMD. Previous extraocular or periocular surgery within 1 month or intraocular surgery (except the surgery mentioned in exclusion 10, such as cataract surgery, etc.) within 3 months prior to dose 1, or current unhealed wound, moderate or severe ulcer or fracture in the study eye. Subconjunctival or intraocular use of corticosteroids within 3 months (including subconjunctival or intraocular long-acting implant within 6 months) prior to dose 1 in the study eye. Use of systemic corticosteroids for 30 or more consecutive days within 3 months prior to dose 1. Inhaled, nasal or dermal steroids are permitted. Topical ocular corticosteroids administered for 30 or more consecutive days in the study eye within 3 months prior to dose 1. Previous systemic anti-VEGF therapy or IVT injection of any anti-VEGF drug into either eye or other ocular use of anti-VEGF drug within 3 months prior to dose 1. Participated in any drug (other than vitamins and minerals) or device clinical trials 3 months or the duration of 5 half-lives of the study drug (which is longer) before the first dose and have used the test drug or received device treatment. Pregnancy or lactation, or fertile men or women not willing to use effective contraception from the day when ICF was signed to at least 6 months following the last dose of study intervention. Infertile women or men fail to meet either of the following ones: 1) menopause (≥12 continuous months of amenorrhea with no identified cause other than menopause before screening); 2) surgically sterilized. Fertile women or men fail to meet either of the following ones: 1) women of childbearing potential must have a negative urine or serum pregnancy test result within 14 days prior to initiation of the study intervention, and should not breastfeed. If the urine pregnancy test is positive, it must be confirmed by a serum pregnancy test; 2) agreement to remain abstinent (refrain from heterosexual intercourse) or use effective contraceptive methods from signed ICF to at least 6 months following the last dose of study intervention. Effective contraceptive methods with a failure rate of <1% per year, including bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone releasing intrauterine devices (IUDs), and copper IUDs. In the Investigator's judgment, there is evidence of a disease or condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or render the participant at high risk for treatment complications (eg stroke or myocardial infarction within 6 months prior to dose 1, uncontrolled hypertension (systolic blood pressure ≥160 mmHg, or diastolic blood pressure ≥100 mmHg), etc.). Uncontrolled diabetes (defined as HbA1c>10.0%). Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) is more than twice the upper limit of normal (ULN), and/or serum creatinine is 1.2 times more than the ULN, and is clinically significant in the opinion of the Investigator. Abnormal coagulation function: prothrombin time(PT) or International normalized ratio (INR) ≥ 1.5 ×ULN, or activated partial thromboplastin time (aPTT) ≥1.5 ×ULN, and is clinically significant in the opinion of the Investigator. Active disseminated intravascular coagulation and obvious bleeding tendency within 3 months prior to dose 1. Evidence of significant uncontrolled concomitant diseases such as cardiovascular diseases, nervous system diseases, respiratory system diseases, urinary system diseases, digestive system diseases and endocrine diseases (eg, stroke, myocardial infarction). Current treatment for active systemic infection, or history of recurrent serious infections. Known active or suspected autoimmune diseases, requiring systemic immunosuppressive therapy. Positive for syphilis screening test human immunodeficiency virus (HIV) infection or positive for HIV screening test. Known allergy to any component of the study intervention or history of allergy to fluorescein or indocyanine green, any anesthetics or antimicrobial agents used during the course of the study. In the Investigator's judgment, other conditions considered not amenable to this study. Participant who has been diagnosed to be COVID-19 within 2weeks prior to the first dose, or still symptomatic from an earlier infection (except symptoms associated with "Long COVID "), or displaying symptoms consistent with COVID-19 in the absence of a confirmed Covid-19 infection.
Information: qi_jin@henlius.com
Study: Study to Evaluate Suprachoroidally Administered CLS-AX in the Treatment of Neovascular Age-Related Macular Degeneration (ODYSSEY)
Clinicaltrials.gov Identifier: NCT05891548
Sponsor: Clearside Biomedical, Inc.
Purpose: Phase 2b, randomized, double-masked, parallel-group, active-controlled, multicenter, 36-week study designed to assess the safety and efficacy of suprachoroidally administered CLS-AX 1.0 mg with a flexible dosing regimen in participants with neovascular age-related macular degeneration previously treated with intravitreal anti-vascular endothelial growth factor (VEGF) standard of care therapy. Only one eye will be chosen as the study eye.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 60
Inclusion Criteria: Diagnosis of neovascular age-related macular degeneration (nAMD) in the study eye within 36 months of Visit 1. Subfoveal choroidal neovascularization (CNV) secondary to nAMD of any lesion type in the study eye that shows total lesion area ≤30 mm2, CNV component area of ≥50% of the total lesion area, and and CNV must not be associated with subfoveal hemorrhage, subfoveal fibrosis, or subfoveal atrophy. Previous treatment in the study eye with between 2 and 4 anti-VEGF intravitreal injections for nAMD (faricimab, ranibizumab, bevacizumab, brolucizumab, or aflibercept) per standard of care within 6 months of Visit 1. History of response to prior intravitreal anti-VEGF treatment in the study eye. ETDRS BCVA of between 20 and 80 letters (inclusive) in the study eye.
Exclusion criteria: ETDRS BCVA <20 letters in the study eye. Central subfield thickness > 400 μm or retinal pigment epithelium detachment thickness >400 μm on SD-OCT in the study eye. Subretinal hemorrhage, fibrosis or atrophy of >50% of the total lesion area and/or that involves the fovea on fundus fluorescein angiography and/or color fundus photography in the study eye. CNV due to causes other than AMD, such are ocular histoplasmosis, trauma, pathological myopia, angioid streaks, choroidal rupture, or uveitis, in the study eye. Any history of macular pathology unrelated to AMD affecting vision or contributing to the presence of intraretinal or subretinal fluid in the study eye.
Information: donna.bezner@clearsidebio.com
Study: Long-term Follow-Up Study of RGX-314 and Fellow Eye Substudy (RGX-314 SRLTFU)
Clinicaltrials.gov Identifier: NCT03999801
Sponsor: Regenxbio Inc.
Purpose: This is a prospective, observational study designed to evaluate the long-term safety and efficacy of RGX-314. Eligible participants are those who were previously enrolled in a clinical study in which they received a single subretinal administration of RGX-314 in their study eye. Enrollment of each participant in the current study should occur after the participant has completed either the end of study or early termination visit in the previous (parent) clinical study. Participants will be followed for up to 5 years post-RGX-314 administration (inclusive of the parent study). After enrollment and a 6-month follow-up visit, participants will attend at least annual study visits through the end of the 5-year post-RGX-314 administration follow-up period. Additionally, an interventional fellow eye treatment substudy will evaluate the safety, efficacy, and immunogenicity of subretinal RGX-314 administration in the fellow eye of participants having bilateral disease who previously received a subretinal injection of RGX-314 in their study eye. Participants who qualify for the substudy will receive subretinal administration of RGX-314 in their fellow eye and complete 13 study visits in a 54-week period. Following completion of the substudy participants will continue in the observational portion of the study for up to 5 years post RGX-314 administration in their fellow eye.
Design: Nonrandomized, single group assignment, no masking
Number of Patients: 865
Inclusion Criteria: Able and willing to provide written consent. Previously enrolled in a clinical study of RGX-314 and received a single subretinal administration of RGX-314.
Exclusion criteria: None.
Study: Effect of AIV007 by Periocular Administration in Subjects With nAMD or DME
Clinicaltrials.gov Identifier: NCT05698329
Sponsor: AiViva BioPharma, Inc.
Purpose: To determine safety, pharmacokinetics, and duration of effect of periocularly administered AIV007 gel suspension in subjects with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).
Design: Nonrandomized, sequential assignment, no masking
Number of Patients: 30
Inclusion Criteria: General: Male or female subjects aged 21-90 years (inclusive) at screening. BCVA in the study eye at screening and baseline/Day 1: ETDRS letter score ≤ 75 and ≥ 24 (20/32 to 20/330 Snellen equivalent). Subject must have received treatment within the 24 months before screening with intravitreal (IVT) injections of an anti-VEGF agent with the last anti-VEGF injection in the study eye being at least 6 weeks (42 days) before baseline/Day 1. Subject has documentation of anti-VEGF responsiveness. Subject must provide written informed consent before any study-related procedures are performed. Clear ocular media and adequate pupil dilation in both eyes to permit good-quality photographic imaging. nAMD subject: The active CNV is confirmed by FA (evidence of leakage). Residual intraretinal or subretinal fluid based on SD-OCT. CST ≥ 300 µm as assessed by SD-OCT. Total lesion size < 10 disc areas (25.4 mm2). Absence of geographic atrophy within 200 µm of the fovea. If subretinal hemorrhage is present, it must be < 50% of the total CNV lesion and/or not involve the fovea. If fibrosis is present, it must be <50% of the total lesion area. DME subject: Diagnosis of diabetes mellitus (Type 1 or Type 2). Subject has clinically significant DME with central involvement (CST≥300 μm by OCT). The decrease in vision in the study eye was determined by the investigator to be primarily the result of DME.
Exclusion Criteria: Previous treatment for nAMD or DME in the study eye other than standard-of-care anti-VEGF IVT injection, eg, cell therapy, brachytherapy, gene therapy. Uncontrolled IOP, defined as an IOP > 25 mmHg. Poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) >10% at screening visit. The spherical equivalent for refractive error in the study eye of worse than 8.0 diopters of myopia (before cataract or refractive surgery) per the current prescription. Any history of active bacterial, viral, fungal, or parasitic ocular or periocular infection, or intraocular inflammation in either eye within the 30 days before the screening visit. History of vitreous hemorrhage within 3 months before screening in the study eye. Uncontrolled systemic disease or any other condition or therapy that would make the participant unsuitable for the study. Participation in any investigational study within 60 days before the screening visit, or planned use of an investigational product or device during the study; any exposure to a prior investigational drug product must be fully washed out (at least 5 half-lives). History of allergy or hypersensitivity to constituents of the study treatment formulation, topical iodine, ocular antimicrobial solutions, or clinically relevant hypersensitivity to fluorescein.
Information: office@aiviva.com
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
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 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: 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: 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: 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: 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: 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
DIABETIC MACULAR EDEMA
NEW: Study: A Phase I Study of Episcleral Dexamethasone for Treatment of Macular Edema
Clinicaltrials.gov Identifier: NCT04005430
Sponsor: Targeted Therapy Technologies, LLC
Purpose: This phase I trial will assess primarily the safety and secondarily anti-inflammatory effect of Episcleral Dexamethasone in patients suffering from refractory diabetic macular edema.
Design: Single group, no masking
Number of Patients: 1
Inclusion Criteria: Type I or II diabetes; Age >= 18 years; Visual acuity letter score in study eye <70 and ≥25 letters (approximate Snellen equivalent 20/32 to 20/320); Ophthalmoscopic evidence of center-involved DME, within the central subfield (CSF); OCT CSF thickness value (microns): Zeiss Cirrus: ≥290 in women; ≥305 in men. Heidelberg Spectralis: ≥305 in women; ≥320 in men. Previous treatment with laser, anti-VEGF therapy and/or intravitreal steroids; No previous history of glaucoma or steroid-induced intraocular pressure response in either eye.
Exclusion Criteria: History of chronic renal failure requiring dialysis or kidney transplant; Retinal or optic nerve neovascularization on clinical exam, fundus photographs, or fluorescein angiograms; Evidence of external ocular infection; History of open-angle glaucoma or intraocular pressure >= 25 mmHg; History of steroid-induced IOP elevation that required IOP-lowering treatment; History of prior herpetic ocular infection; History of intravitreal or periocular corticosteroids within 3 months prior to enrollment; History of macular laser photocoagulation within 4 months prior to enrollment; History of antiangiogenic therapy within 4 weeks prior to enrollment; History of panretinal photocoagulation (PRP) within 4 months prior to enrollment or anticipated need for PRP in the next 6 months following enrollment; Presence of vitreomacular traction, epiretinal membrane, tractional retinal detachment, vitreous hemorrhage and or any ocular condition that the investigator judges could interfere in the safety and efficacy assessments; No other major non-diabetic pathology, or anticipation of such in the next 6 months following enrollment that in the opinion of the investigator would substantially and adversely affect assessment of safety and toxicity during the study; Participation in another clinical trial of non-approved medical treatment within 3 months prior to enrollment; Degenerative myopia; Malignant intraocular disease; Inability to understand informed consent, cooperate with testing or return to follow up visits; Pregnant or lactating women; Co-existent ocular disorder of the cornea, lens or media that will interfere with assessment of safety or efficacy.
NEW: Study: A Phase 2 Study to Assess the Efficacy and Safety of KHK4951 in Patients With Diabetic Macular Edema
Clinicaltrials.gov Identifier: NCT06116916
Sponsor: Kyowa Kirin, Inc.
Purpose: The purpose of this study is to evaluate efficacy and safety of KHK4951 eye drops in patients with DME.
Design: Randomized, parallel assignment
Number of Patients: 150
Inclusion Criteria: Voluntary written informed consent to participate in the study. BCVA ETDRS letter score of 73 letters to 35 letters as measured by the ETDRS visual acuity chart in the study eye at screening. 500 μm ≥ CST ≥ 325 μm in the study eye at screening. HbA1c ≤11% at screening.
Exclusion Criteria: Any signs of proliferative diabetic retinopathy in the study eye. History of rubeosis in the study eye. Uncontrolled glaucoma in the study eye. Aphakia or pseudophakia with AC-IOL in the study eye. Active intraocular inflammation in the study eye. Any current ocular condition for which visual acuity loss would not improve from resolution of macular edema in the study eye. History of rhegmatogenous retinal detachment 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. History of the following therapies in the study eye. History of vitrectomy surgery, submacular surgery, or other surgical intervention for DME. Previous use of periocular or intraocular (sub-Tenon or IVT) corticosteroids. Previous intraocular device implantation except PC-IOL. Previous laser (any type) to the macular area. Previous panretinal photocoagulation treatment. Previous treatment with any IVT anti-VEGF drugs. Previous use of Ozurdex or Iluvien implant. Any current or history of endophthalmitis in either eye. History of idiopathic or autoimmune-associated uveitis in either eye. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
Information: teppei.kurosawa.gx@kyowakirin.com
Study: 4D-150 in Patients With Diabetic Macular Edema
Clinicaltrials.gov Identifier: NCT05930561
Sponsor: 4D Molecular Therapeutics
Purpose: Phase 2 randomized, active-controlled, double-masked, dose-ranging trial in adults with diabetic macular edema (DME).
Design: Randomized, parallel assignment, double masking
Number of Patients: 72
Inclusion Criteria: ≥18 years of age. Type I or type II diabetes mellitus with macular thickening secondary to DME involving the center of the fovea. Demonstrate clinical response to on-study aflibercept injection in the study eye. Decreased visual acuity attributable primarily to DME. BCVA in the study eye between 25 and 83 ETDRS letters, inclusive (~20/320 and 20/25, respectively) at screening. Study eye amenable to IVT injection. Sufficient clear ocular media, pupil dilation and fixation in the study eye to permit adequate imaging; ability to perform tests of visual and retinal function and structure; and ability to comply with other protocol-specified procedures. Provide written informed consent.
Exclusion Criteria: Macular edema in the study eye considered to be secondary to a cause other than DME. Systemic anti-VEGF treatment (eg sunitinib, bevacizumab, pazopanib) within 6 months, or anticipated need for systemic anti-VEGF therapy during study participation. Systemic corticosteroids (oral, intravenous, intramuscular, intra-articular) or other immunosuppressive medications within 3 months. Received an investigational drug, agent, device, or therapy (ocular or non-ocular) in the 6 months or at least 5 half-lives (whichever is longer) prior to screening. Prior gene therapy (ocular or non-ocular) and/or ocular stem cell therapy in either eye. Any concurrent ocular condition in the study eye that is likely to require surgical intervention (eg cataract surgery) during the 2 year (104 week) study duration.
Information: clinicaltrials@4DMT.com
Study: Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With DME (ASPIRE)
Clinicaltrials.gov Identifier: NCT06011798
Sponsor: Unity Biotechnology, Inc.
Purpose: The goal of this clinical trial is to assess the efficacy and safety of multiple doses of foselutoclax (UBX1325) in patients with diabetic macular edema. The main question(s) the study aims to answer are: assess the efficacy of foselutoclax compared to aflibercept; and assess the safety and tolerability of foselutoclax.
Design: Randomized, parallel assignment, triple masking
Number of Patients: 40
Inclusion Criteria: Patients aged ≥18 years. Patients with nonproliferative DR and DME. Center-involved DME with central subfield thickness (CST) ≥325-900 μm. BCVA in the SE (most affected) of 70 to 30 ETDRS letters (equivalent to 20/40 to 20/250 on the Snellen chart).
Exclusion Criteria: Patients aged ≥18 years. Patients with nonproliferative DR and DME. Center-involved DME with Central Subfield Thickness (CST) ≥325-900 μm. BCVA in the SE (most affected) of 70 to 30 ETDRS letters (equivalent to 20/40 to 20/250 on the Snellen chart).
Information: UBX1325_medicalmonitor@unitybiotechnology.com
Study: Evaluation of Tonabersat for DME (AN)
Clinicaltrials.gov Identifier: NCT05727891
Sponsor: Jaeb Center for Health Research
Purpose: This randomized clinical trial will evaluate the effect of tonabersat compared with placebo on central subfield thickness (CST) in eyes with center-involved diabetic macular edema (CI-DME) and good visual acuity.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 128
Inclusion Criteria: Adults with type 1 or 2 diabetes mellitus. At least one eye with: best corrected E-ETDRS visual acuity letter score ≥79 (ie, 20/25 or better); ophthalmoscopic evidence of center-involved DME in study eye confirmed by central subfield thickness on spectral domain OCT; Zeiss Cirrus: ≥290 µm in females, ≥305 µm in males; Heidelberg Spectralis: ≥305 µm in females, ≥320 µm in males; recruitment will be monitored with a goal to have equal proportions in the following categories above the CI-DME thresholds: <75 μm, 75 μm to <175 μm, ≥175 μm. Media clarity, pupillary dilation, and study participant cooperation sufficient for adequate OCT.
Exclusion Criteria: Macular edema is considered to be due to a cause other than DME. Major ocular surgery within prior 4 months, or anticipated after randomization. History of focal/grid laser or other ocular surgical, intravitreal, or peribulbar treatment for DR or DME within prior 1 year, and no more than 4 prior anti-VEGF injections total. Anticipated need to treat DME or DR during the first 6 months, or anticipated need for cataract surgery during study period. Any history of vitrectomy. Systemic anti-VEGF or pro-VEGF treatment within 12 months prior to randomization. History of chronic renal failure requiring dialysis or kidney transplant. History of moderate to severe hepatic impairment, including known liver function test (LFT) values > 3x's the upper limit of normal.
Information: drcrnet@jaeb.org
Study: Treat & Extend Versus Fixed Dosing With Faricimab for Management of Diabetic Macular Edema: A Pragmatic, Multi-center, Open-label, Randomized, Controlled Trial (INSITE-DME)
Clinicaltrials.gov Identifier: NCT05610319
Sponsor: McMaster University
Purpose: This study will assess a pragmatic, treat and extend regimen of faricimab against the standard of a fixed dosing regimen.
Design: Randomized, parallel assignment, single masking
Number of Patients: 446
Inclusion Criteria: Age ≥18 years. Diagnosis of diabetes mellitus (type 1 or type 2). Macular thickening secondary to DME (CI-DME) involving the center of the fovea on optical coherence tomography - central subfield thickness (CST) ≥325 μm on Spectralis at screening. Visual impairment due to DME, with best corrected visual acuity of 80 to 20 letters (Snellen VA 20/25 to 20/400). Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCT and fundus photographs. Hemoglobin A1c must be <10% within 2 months prior to 1st study treatment. Provide signed informed consent.
Exclusion Criteria: Active or history of ocular inflammation or suspected/active ocular infection in either eye. High-risk proliferative diabetic retinopathy in the study eye. Tractional retinal detachment, preretinal fibrosis or visually significant epiretinal membrane involving the macula. Uncontrolled glaucoma (intraocular pressure >30 with or without medications). Any intravitreal, periocular or implant corticosteroids within 26 weeks (6 months) before day 1 or any use of Iluvien implants. Treatment with Panretinal photocoagulation (PRP) within 12 weeks before day 1. Treatment with macular laser. Any cataract surgery or any other intraocular surgery within 12 weeks before day 1. Macular edema in study eye due to a cause other than DME. If clinical exam and/or OCT and/or wide-field fluorescein angiography (WF-FA) suggest that (a) macular edema is considered to be related to ocular surgery such as cataract extraction or (b) if primary cause for macular edema is vitreoretinal interface abnormalities (eg, a taut posterior hyaloid or epiretinal membrane). Any ocular condition is present such that visual acuity loss would not improve from resolution of macular edema in opinion of the investigator (eg, foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition). Any history of ocular conditions that might affect macular edema (eg, vein occlusion, idiopathic or infectious or non-infectious uveitis, ocular inflammatory disease, neovascular glaucoma etc.). Women of child-bearing potential who are lactating, pregnant, or intending to become pregnant within the next 100 weeks. Current or anticipated incarceration. Terminal illness with expected survival less than 100 weeks. Known hypersensitivity to faricimab or any of the excipients in the faricimab injection. Currently enrolled in a study that does not permit co-enrollment. Unable to obtain informed consent due to language or other operational barriers. Anticipated problems, in the judgment of the site investigator, maintaining compliance with the protocol, including attending study visits, completing assessments or procedures. Prior enrollment in this trial. Other reason to exclude the patient, as approved by the sponsor and site investigator. Previous treatment with anti-VEGF and: <12 weeks prior to day 1 (washout period) or, diagnosis of DME is > 2 years of enrollment or, do not have a demonstrated response to anti-VEGF treatment based on clinical discretion.
Information: delfabbg@mcmaster.ca
Study: Suprachoroidal Sustained-Release OXU-001 Compared to Intravitreal Ozurdex in the Treatment of Diabetic Macular Edema (OXEYE)
Clinicaltrials.gov Identifier: NCT05697809
Sponsor: Oxular Limited
Purpose: The purpose of this clinical trial is to compare safety, tolerability, efficacy, and durability of two dose levels of suprachoroidal sustained-release OXU-001 (dexamethasone microspheres; DEXAspheres) using the Oxulumis illuminated microcatheterization device compared with intravitreal dexamethasone implant (Ozurdex) in subjects with diabetic macular edema.
Design: Randomized, parallel assignment, triple masking
Number of Patients: 128
Inclusion Criteria: Type 1 or type 2 diabetes mellitus. Diabetic macular edema involving the center of the fovea in the study eye. Best corrected visual acuity in the study eye between 34 and 78 (early treatment of diabetic retinopathy study) ETDRS letters.
Exclusion Criteria: Macular edema is considered due to a cause other than diabetes mellitus in the study eye. Condition, in the study eye, in which visual acuity is not expected to improve from the resolution of macular edema. Macular laser photocoagulation or panretinal laser photocoagulation in the study eye performed within 16 weeks prior to screening. Active proliferative diabetic retinopathy (PDR) or sequelae of PDR in the study eye. Prior treatment with anti-VEGF in the study eye: treatment naïve group (Part B), any IVT anti-VEGF treatments in the study eye are exclusionary regardless of the time interval since injection. Previously treated group (Part A and B), subjects in the previously treated group are excluded if they meet any of the below criteria for the study eye at screening: subject has received less than 3 anti-VEGF injections since treatment initiation (at least three injections must have been received for eligibility). Time interval between the first anti-VEGF injection and screening is more than 40 weeks. Last injection with ranibizumab or bevacizumab within 4 weeks prior to screening. Last injection with aflibercept within 8 weeks prior to screening. Last injection with faricimab or brolucizumab within 12 weeks prior to screening. Prior treatment with SUSVIMO (Port Delivery System) implant is exclusionary. Prior ocular treatment with steroid injections (periocular, subtenon, intravitreal) or intravitreal implants in the study eye. Prior treatment with suprachoroidal steroids in the study eye is exclusionary. Active malignancy or history of malignancy within the past 5 years. Uncontrolled diabetes with a hemoglobin A1c (HbA1c) more than 12% or any other uncontrolled systemic disease at screening.
Information: clinicaltrials@oxular.com
Study: A 2-part Study Consisting of Multiple Ascending Dose (MAD) Safety Study, and a Dose-finding Masked Study to Assess the Safety and Efficacy of Intravitreal (IVT) EYE103 in Patients With Diabetic Macular Edema (DME) or Neovascular Age-related Macular Degeneration (NVAMD) (AMARONE)
Clinicaltrials.gov Identifier: NCT05919693
Sponsor: EyeBiotech Ltd.
Purpose: EYE103-101 is a 2-part study assessing safety and preliminary efficacy of EYE103 in patients with diabetic macular edema (DME) given as monotherapy or neovascular macular degeneration (NVAMD) given in combination with anti-VEGF.
Design: Randomized, sequential assignment, triple masking
Number of Patients: 92
Inclusion Criteria: Be willing and able to understand the study procedures and the risks involved and provide written informed consent before the first study-related activity. DME patients must be ≥18 years of age, NVAMD patients must be ≥50 years of age. Diagnosis of either DME or NVAMD. DME patients must be treatment naïve. NVAMD patients can be either treatment naïve or treatment experienced. DME patients must have vision loss in the study eye. NVAMD patients can be either treatment-naïve or treatment experienced with vision loss in the study eye.
Exclusion Criteria: Be pregnant or breastfeeding. History of cataract surgery and/or minimally invasive glaucoma surgery (MIGS) within 3 months of screening. Yttrium-Aluminum Garnet (YAG) laser capsulotomy within 2 months of screening. Any other condition except for DME or NVAMD or that could affect interpretation of study assessments.
Information: ClinicalInquiries@eyebiotech.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/Allergan
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: 23
Inclusion Criteria: Signed informed consent. Men and women ≥ 18 years of age. Foveal-involving retinal edema secondary to DME based on investigator review of SD-OCT. Central subfield thickness on SDOCT of greater than or equal to 325 microns on Spectralis or 300 microns on Cirrus. E-ETDRS best-corrected visual acuity of 20/400 or better in the study eye. Willing, committed, and able to return for ALL clinic visits and complete all study related procedures. Able to read, (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member) understand and willing to sign the informed consent form.
Exclusion Criteria: Any prior or concomitant therapy with another investigational agent to treat DME in the study eye. Prior panretinal photocoagulation in the study eye. Prior intravitreal anti-VEGF therapy in the study eye. Prior focal/grid laser photocoagulation in the study eye. Prior history of intravitreal steroid therapy in the study eye. Any history of severe allergy to fluorescein sodium (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 diopters or more negative, or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, choroidal neovascularization, age-related macular degeneration or multifocal choroiditis in the study eye. Epiretinal membranes are allowed. Presence of macula-threatening traction retinal detachment in the study eye. Prior vitrectomy in the study eye. History of retinal detachment or treatment or surgery for retinal detachment in the study eye. Any history of macular hole of stage 2 and above in the study eye. Any intraocular or periocular surgery within 3 months of Day 1 in the study eye, except lid surgery, which may not have taken place within 1 month of day 1, as long as it's unlikely to interfere with the injection. Prior trabeculectomy or other filtration surgery in the study eye. Any ocular or periocular infection within the last 2 weeks prior to Screening in either eye. Any history of uveitis in either eye. Active scleritis or episcleritis in either eye. Presence or history of scleromalacia in either eye. Aphakia in the study eye. Previous therapeutic radiation in the region of the study eye. History of corneal transplant or corneal dystrophy in the study eye. Significant media opacities, including cataract, in the study eye which might interfere with visual acuity, assessment of safety, or fundus photography. Any concurrent intraocular condition in the study eye (eg, cataract) that, in the opinion of the investigator, could require either medical or surgical intervention during the study period. Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the subject beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety. Participation as a subject in any clinical study within the 12 weeks prior to Day 1. Any systemic therapy with an investigational agent in the past 3 months prior to Day 1. Any history of allergy to povidone iodine. Pregnant or breast-feeding women: Women of childbearing potential* who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly) *Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
Information: Justis Ehlers, The Norman C. and Donna L. Harbert Endowed Chair of Ophthalmic Research, The Cleveland Clinic
Study: Oxulumis Suprachoroidal Microcatherization of Triesence in Diabetic Macular Edema (CAPE)
Clinicaltrials.gov Identifier: NCT05512962
Sponsor: Oxular Limited
Purpose: The purpose of this clinical trial is to evaluate the safety and tolerability of suprachoroidal microcatheterization with the Oxulumis® device for a randomized treatment with two dose levels of Triesence® in subjects with Diabetic Macular Edema.
Design: Randominzed, parallel assignment, single masking
Number of Patients: 20
Inclusion Criteria: Type 1 or Type 2 diabetes mellitus. Diabetic macular edema involving the center of the fovea in the study eye. Best-corrected visual acuity in the study eye of ≤73 (early treatment of diabetic retinopathy study) ETDRS letters (approximate Snellen equivalent of 20/40 or worse). Short-lived, limited, or no response to prior ocular injection therapy.
Exclusion Criteria: Macular edema is considered due to a cause other than diabetes mellitus in the study eye. Condition, in the study eye, in which visual acuity is not expected to improve from the resolution of macular edema. Macular laser photocoagulation or panretinal laser photocoagulation in the study eye performed within sixteen (16) weeks prior to screening. Active proliferative diabetic retinopathy (PDR) or sequelae of PDR in the study eye. Active malignancy or history of malignancy within the past 5 years. Prior intravitreal (IVT) treatment with anti-vascular endothelial growth factor (VEGF) in the study eye: last injection within four weeks, before screening. Prior ocular treatment with steroids in the study eye: last injection (intra- or periocular) with triamcinolone acetonide within three (3) months, with dexamethasone implant (Ozurdex) within six (6) months before screening. Prior treatment with longer duration steroid implants (eg, fluocinolone acetonide IVT implant, Iluvien) is exclusionary. Prior treatment with suprachoroidal steroids is exclusionary. Uncontrolled diabetes with a hemoglobin A1c (HbA1c) >12% or any other uncontrolled systemic disease at screening.
Information: clinicaltrials@oxular.com
Study: Study to Evaluate the Efficacy and Safety of RZ402 in Diabetic Macular Edema (DME)
Clinicaltrials.gov Identifier: NCT05712720
Sponsor: Rezolute
Purpose: The objective of this trial is to assess the safety, efficacy, and tolerability of RZ402 in patients with diabetic macular edema.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 100
Inclusion Criteria: Confirmed diabetes mellitus Type 1 or Type 2. Stable glycemic control. Study Eye Inclusion Criteria: Mild to moderate non-proliferative diabetic retinopathy (NPDR) with retinal thickening due to CI-DME as determined by the Investigator. Spectral Domain Optical Coherence Tomography (SD-OCT) foveal CST at screening measuring ≥320 µm (or corresponding values). Best Corrected Visual Acuity ETDRS letter score at 4 meters of ≤78 letters at screening. Media clarity, pupillary dilation, and participant cooperation sufficient for adequate clinical evaluations, OCT images and fundus photographs, at screening. Fellow Eye Inclusion Criteria: Best Corrected Visual Acuity ETDRS letter score at 4 meters of ≥5 letters at screening.
Exclusion Criteria: Received more than 3 anti-VEGF injections (including Avastin) and/or received a recent anti-VEGF injection within 8 weeks of Randomization. Any history of retinal surgery or other surgical intervention for DME. Intraocular surgery (including cataract surgery), within 12 weeks prior to Randomization, or anticipated need for ocular surgery during the study period. History of trabeculectomy or other filtration surgery (prior laser trabeculoplasty and placement of iStent in conjunction with cataract surgery is permitted if the procedure took place ≥12 weeks prior to Randomization). Autoimmune idiopathic inflammatory eye disease such as anterior uveitis, or participants with history or signs of chronic inflammation. Full thickness macular hole or retinal detachment. Panretinal, macular focal, or grid laser photocoagulation within 16 weeks of Randomization or anticipated need for the use of laser photocoagulation during the study period. Uncontrolled glaucoma, at screening, defined as IOP ≥25 mmHg. The use of corticosteroids as follows: Topical corticosteroids within 12 weeks prior to Randomization and throughout the remainder of the study. Use of intraocular or sub-Tenon's steroids within 2 years of Randomization in phakic eyes or 9 months of Randomization in pseudophakic eyes, and throughout the remainder of the study. Fellow Eye Exclusion Criteria: Intraocular or sub-Tenon's steroid injection within 6 months of Randomization and throughout the remainder or the study. Use of the following medications or substances within the specified timeframes below and throughout the remainder of the study. a. Within 16 weeks of Randomization: i. Systemic anti-VEGF or pro-VEGF treatments ii. Systemic, approved, or off-label drugs or devices used to treat DME iii. Participated in an investigational drug or device study within 16 weeks or 5 half-lives (whichever is longer) of Randomization, including systemic or ocular studies iv. Initiation of drugs or substances known to improve or worsen macular edema eg, Latanoprost or phosphodiesterase-5 (PDE-5) inhibitors (eg, Sildenafil or others in PDE-5 class), but participants may remain on these drugs if they were initiated >16 weeks prior to Randomization. b. Within 12 weeks of Randomization: i. Use of tobacco- or nicotine- containing products (eg, cigarettes, cigars, chewing tobacco, snuff, vaping). c. Within 4 weeks of Randomization: i. Anti-coagulants, except for aspirin ≤325 mg/day and/or clopidogrel ≤75 mg/day (or equivalent drug class) ii. Total daily doses of Metformin >1000 mg iii. Total daily doses of niacin (Vitamin B3) >1.5 g/day iv. Use of systemic steroids at supraphysiologic doses (eg, prednisone equivalent of 5 mg/day or hydrocortisone equivalent of 20 mg/day). v. Drugs that may affect the retina or optic nerve such as quinolones, thioridazine, deferoxamine, ethambutol, vigabatrin, and pentosan. Alanine aminotransferase (ALT), or aspartate aminotransferase (AST), or alkaline phosphatase (ALP) ≥2X upper limit of normal (ULN), total bilirubin ≥1.5X ULN, or gamma-glutamyl transferase (GGT) ≥3X ULN as per the central laboratory. Estimated glomerular filtration rate (eGFR) at ≤45 mL/min and/or history of persistent micro or macro albuminuria. History of current or prior (within 1 year of Randomization) any significant illness, or any medical history. History of bariatric surgery or other surgical or medical history. History of current or prior (within 1 year of Randomization) abnormal, clinically significant ECG including inadequately controlled hypertension. History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding. Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury. Known history of human immune-deficiency virus (HIV), hepatitis C, or hepatitis B infection. Malignancies within 3 years prior to Randomization. Donated more than 500 mL of blood or significant blood loss within 60 days before Randomization.
Information: RZ402clinicaltrials@rezolutebio.com
Study: Effect of AIV007 by Periocular Administration in Subjects With nAMD or DME
Clinicaltrials.gov Identifier: NCT05698329
Sponsor: AiViva BioPharma, Inc.
Purpose: To determine safety, pharmacokinetics, and duration of effect of periocularly administered AIV007 gel suspension in subjects with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).
Design: Nonrandomized, sequential assignment, no masking
Number of Patients: 30
Inclusion Criteria: General: Male or female subjects aged 21-90 years (inclusive) at screening. BCVA in the study eye at screening and baseline/Day 1: ETDRS letter score ≤ 75 and ≥ 24 (20/32 to 20/330 Snellen equivalent). Subject must have received treatment within the 24 months before screening with intravitreal (IVT) injections of an anti-VEGF agent with the last anti-VEGF injection in the study eye being at least 6 weeks (42 days) before baseline/Day 1. Subject has documentation of anti-VEGF responsiveness. Subject must provide written informed consent before any study-related procedures are performed. Clear ocular media and adequate pupil dilation in both eyes to permit good-quality photographic imaging. nAMD subject: The active CNV is confirmed by FA (evidence of leakage). Residual intraretinal or subretinal fluid based on SD-OCT. CST ≥ 300 µm as assessed by SD-OCT. Total lesion size < 10 disc areas (25.4 mm2). Absence of geographic atrophy within 200 µm of the fovea. If subretinal hemorrhage is present, it must be < 50% of the total CNV lesion and/or not involve the fovea. If fibrosis is present, it must be <50% of the total lesion area. DME subject: Diagnosis of diabetes mellitus (Type 1 or Type 2). Subject has clinically significant DME with central involvement (CST≥300 μm by OCT). The decrease in vision in the study eye was determined by the investigator to be primarily the result of DME.
Exclusion Criteria: Previous treatment for nAMD or DME in the study eye other than standard-of-care anti-VEGF IVT injection, eg, cell therapy, brachytherapy, gene therapy. Uncontrolled IOP, defined as an IOP > 25 mmHg. Poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) >10% at screening visit. The spherical equivalent for refractive error in the study eye of worse than 8.0 diopters of myopia (before cataract or refractive surgery) per the current prescription. Any history of active bacterial, viral, fungal, or parasitic ocular or periocular infection, or intraocular inflammation in either eye within the 30 days before the screening visit. History of vitreous hemorrhage within 3 months before screening in the study eye. Uncontrolled systemic disease or any other condition or therapy that would make the participant unsuitable for the study. Participation in any investigational study within 60 days before the screening visit, or planned use of an investigational product or device during the study; any exposure to a prior investigational drug product must be fully washed out (at least 5 half-lives). History of allergy or hypersensitivity to constituents of the study treatment formulation, topical iodine, ocular antimicrobial solutions, or clinically relevant hypersensitivity to fluorescein.
Information: office@aiviva.com
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 Spectra Study to Evaluate the Safety and Efficacy of OPL-0401 in Patients With Diabetic Retinopathy
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: 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: 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: 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: 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: 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: Episcleral Dexamethasone for Treatment of Macular Edema and Inflammatory Disorders of the Posterior Pole
Clinicaltrials.gov Identifier: NCT04120311
Sponsor: Targeted Therapy Technologies, LLC
Purpose: This phase 1 trial will assess primarily the safety and secondarily anti-inflammatory effect of episcleral dexamethasone in patients suffering from macular edema and other disorders of the retina, choroid and vitreous.
Design: Single group, no masking
Number of Patients: 2
Inclusion Criteria: Age ≥8 years; visual acuity letter score in study eye < 70 and ≥ 25 letters (approximate Snellen equivalent 20/32 to 20/320); ophthalmoscopic evidence of center-involved macular edema, within the central subfield (CSF); inflammatory disorders of the sclera, choroid, retina or vitreous.
Exclusion Criteria: Inability to understand informed consent, cooperate with testing or return to follow up visits; pregnant or lactating women; co-existent ocular disorder of the cornea, lens or media that will interfere with assessment of safety or efficacy.
Study: A Study to Learn How Well a Higher Amount of Aflibercept Given as an Injection Into the Eye Works and How Safe it is in People With Reduced Vision Due to Swelling in the Macula, Central Part of the Retina Caused by a Blocked Vein in the Retina (Macula Edema Secondary to Retinal Vein Occlusion) (QUASAR)
Clinicaltrials.gov Identifier: NCT05850520
Sponsor: Bayer
Purpose: A study to learn how well a higher amount of aflibercept given as an injection into the eye works and how safe it is in people with reduced vision due to swelling in the macula, central part of the retina caused by a blocked vein in the retina (macula edema secondary to retinal vein occlusion) (QUASAR)
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 822
Inclusion Criteria: Adult ≥18 years of age (or country's legal age of adulthood if the legal age is >18 years) at the time of signing the informed consent. Treatment-naïve macular edema involving the foveal center secondary to RVO (BRVO, HRVO, or CRVO) diagnosed within 16 weeks (112 days) before the screening visit in the study eye. Early Treatment Diabetic Retinopathy Study BCVA letter score of 73 to 24 (20/40 to 20/320) at screening and baseline visits in the study eye. Decrease in BCVA determined to be primarily the result of RVO in the study eye. Mean CST ≥300 μm on optical coherence tomography (OCT) if excluding Bruch's membrane (eg, Cirrus or Topcon) or ≥320 μm if including Bruch's membrane (eg, Heidelberg Spectralis), confirmed by the reading center at the screening visit and by the site at baseline visit in the study eye. Capable of giving signed informed consent form (ICF) by study participant or legally acceptable representative, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. US participants will be required to have a Health Insurance Portability and Accountability Act (HIPAA) authorization; in other countries, as applicable according to national laws. Women of childbearing potential (WOCBP) or men who are sexually active with partners of childbearing potential must agree to use highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 4 months after the last administration of study intervention. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for participation in clinical studies and fulfil the conditions set on Section 10.4.2.
Exclusion Criteria: Concurrent disease that causes substantial decrease of BCVA, is expected to limit BCVA recovery or is likely to require medical or surgical intervention during the study in the study eye. Presence or history of the following ocular conditions: Advanced age-related macular degeneration (neovascular AMD or geographic atrophy) in the study eye. Diabetic macular edema or diabetic retinopathy, defined in diabetic participants as diabetic retinopathy lesions outside the area of the vein occlusion in the study eye and anywhere in the retina in the fellow eye. Anterior segment neovascularization, vitreous hemorrhage, retinal detachment in the study eye. Vitreomacular traction, epiretinal membrane or structural damage to the macula that is considered by the Investigator to significantly affect central vision or preclude improvement in vision in the study eye. Macular hole of stage 2 and above in the study eye. Myopia of a spherical equivalent of at least 8 diopters prior to any refractive or cataract surgery in the study eye. Corneal transplant or corneal dystrophy in the study eye. Idiopathic or autoimmune uveitis in the study or in the fellow eye. Presence of the following ocular conditions at screening or baseline visit: Significant media opacities, including cataract, that interfere with BCVA, or imaging assessments (eg, fundus photography [FP], OCT) in the study eye. Aphakia, or pseudophakia with absence of posterior capsule (unless it occurred as a result of a yttrium-aluminum-garnet [YAG] posterior capsulotomy performed more than 30 days before the screening visit), in the study eye. Uncontrolled glaucoma (defined as IOP >25 mmHg despite treatment with anti-glaucoma medication); or history or likely future need of glaucoma surgery in the study eye. Intraocular inflammation/infection (including trace, or above, cells in the anterior chamber and/or vitreous) within 12 weeks (84 days) of the screening visit in the study or in the fellow eye. Extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in the study or in the fellow eye. Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg) at the screening visit or baseline visit. Uncontrolled diabetes mellitus, defined by hemoglobin A1c (HbA1c) >12% at the screening visit. History of cerebrovascular accident or myocardial infarction within 24 weeks (168 days) before the screening visit or between screening and baseline visits. Renal failure requiring dialysis, or renal transplant at screening or potentially during the study. Any prior or concomitant ocular or systemic treatment (with an investigational or approved, anti-VEGF or other agent) or surgery for RVO in the study eye. Previous administration of systemic anti-angiogenic medications for any condition. Prior treatment of the study eye with any of the following drugs (any route of ophthalmic administration) or procedures: Anti-angiogenic drugs at any time including investigational therapy (eg, with anti-angiopoietin/anti-VEGF bispecific monoclonal antibodies). Previous use topical steroids within 4 weeks (28 days) from the screening visit, or intraocular or periocular steroids within 16 weeks (112 days) from the screening visit, or steroid implants at any time. Previous treatment with intraocular or periocular implant, gene therapy, or cell therapy at any time. Treatment with ocriplasmin at any time. Vitreoretinal surgery (including scleral buckling) at any time. Any intraocular surgery, including cataract surgery, within 12 weeks (84 days) before the screening visit. Previous treatment with retinal laser photocoagulation. Prior treatment of the fellow eye with any of the following: a. Gene therapy, or cell therapy in the fellow eye at any time. Participation in other clinical studies requiring administration of investigational treatments (other than vitamins and minerals) at the time of screening visit, or within 30 days or 5 half-lives of administration of the previous study intervention, whichever is longer.
Information: clinical-trials-contact@bayer.com
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: 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: Adalimumab in JIA-associated Uveitis Stopping Trial (ADJUST)
Clinicaltrials.gov Identifier: NCT03816397
Sponsor: Nisha Acharya
Purpose: The proposed study is a stratified, block-randomized, double-masked, controlled trial to determine the feasibility of discontinuing adalimumab treatment in patients with quiescent uveitis associated with juvenile idiopathic arthritis (JIA) or chronic anterior uveitis (CAU).
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 118
Inclusion Criteria: Stated willingness to comply with all study procedures and availability for the duration of the study period. ≥2 years of age. History of JIA or CAU diagnosed prior to 16 years of age (patient may be older than 16 at time of enrollment). Formal diagnosis of JIA-associated uveitis or CAU with no other suspected etiology. ≥12 consecutive months of controlled ocular inflammation (≤0.5+ anterior chamber cell, ≤0.5+ vitreous haze, no active retinal/choroidal lesions in either eye). ≥ 12 consecutive months of controlled arthritis verified by a pediatric rheumatologist, if defined as JIA-associated uveitis. ≥12 consecutive months of treatment with adalimumab or a biosimilar of adalimumab. ≥180 days on a stable dose of adalimumab or a biosimilar; must be biweekly dose of either 20mg (if<30kg) or 40mg (if ≥30kg). If on a biosimilar of adalimumab, ≥90 days on the biosimilar. If on concomitant antimetabolite (injectable or oral methotrexate, mycophenolate mofetil, azathioprine, or leflunomide), dose must be ≤25 mg weekly for methotrexate, ≤3 g daily for mycophenolate mofetil, ≤250 mg daily for azathioprine, or ≤20 mg daily for leflunomide; dose and route of administration must be stable for ≥90 days. If on topical corticosteroids, dose must be ≤2 drops prednisolone acetate 1% or equivalent per day and stable for ≥90 days. Willingness to limit consumption of alcohol during the study period. Agreement to avoid live attenuated vaccinations. Agreement to use highly effective contraception for ≥28 days prior to screening and throughout study period (for males and females of reproductive age). Suitable, in the opinion of the Investigator, to continue treatment with adalimumab or placebo per regional labeling. No contraindications to receive adalimumab as per the local Summary of Product Characteristics (SmPC).
Exclusion Criteria: Intraocular surgery in the past 90 days or planned surgery in the next 12 months. Severe cataract or opacity preventing view to the posterior pole in both eyes. Chronic hypotony (<5mmHg for ≥90 days) in either eye. Treatment with oral corticosteroids or intraocular corticosteroid injection within the last 12 months. Use of NSAID eye drops within the last 90 days. Acute anterior uveitis characterized by redness and symptoms, including but not limited to floaters, pain, and light sensitivity. Pregnancy or lactation (a pregnancy test will be conducted at baseline and all follow-up visits for females of reproductive age). Presence of intraretinal or subretinal fluid in either eye. Prior safety or tolerability issues with adalimumab. History of cancer, active tuberculosis, or hepatitis B. Other medical condition expected to dictate treatment course during the study. Any of the following laboratory test results on their most recent tests within the past 90 days prior to screening/enrollment: leukocyte count <2500, platelet count ≤75000, hemoglobin<9.0, AST or ALT ≥ 2 times the upper limit of normal range, creatinine ≥1.5. There are no sex, race, or ethnicity restrictions for this study.
Information: nisha.acharya@ucsf.edu
Study: POC Study to Evaluate the Efficacy and Safety of ESK-001 in Patients With Active Intermediate, Posterior, or Pan NIU (OPTYK-1)
Clinicaltrials.gov Identifier: NCT05953688
Sponsor: Alumis Inc
Purpose: This is a multi-center, randomized, double-masked, proof-of-concept study in patients with active noninfectious intermediate, posterior, or panuveitis.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 30
Inclusion Criteria: Able and willing to provide consent. Male and females, age 18 to 70 years. Diagnosis of active noninfectious intermediate, posterior or panuveitis. Must have active uveitis at Screening in at least one eye as defined by: active inflammatory chorioretinal and/or inflammatory retinal vascular lesion or lesions, or ≥2+ VH in accordance with the NEI/SUN criteria. Males and females must use highly effective methods of contraception for the entirety of the study.
Exclusion Criteria: Diagnosis of infectious uveitis. Has elevated intraocular pressures or severe glaucoma. Positive for HIV, Hepatitis B or C or active or inadequately latent tuberculosis at screening. Positive for syphilis at screening. Patients with QTcF >450 msec (both males and females) at screening. Known active malignancy or history of malignancy within the past 5 years. History of chronic drug or alcohol abuse. Live vaccines. No planned ocular or any other surgery during the course of the study. Other protocol-defined inclusion/exclusion criteria apply.
Information: clinicaltrials@alumis.com
Study: Multicenter Study on the Efficacy and Safety of OCS-01 in Subjects With Uveitis Related and Post Surgical Macular Edema (LEOPARD)
Clinicaltrials.gov Identifier: NCT05608837
Sponsor: Quan Dong Nguyen/Global Ophthalmic Research Center (GORC) and Oculis
Purpose: The goal of the LEOPARD clinical trial is to investigate a new kind of steroid eye drops, OCS-01. In the LEOPARD study the investigators wish to see how safe is the study drug (OCS-01) and how well it works, in resolving the fluid collection in the eye in patients with Uveitis or in patients who have had eye surgery.
Design: Randomized, parallel assignment, double masking
Number of Patients: 24
Inclusion Criteria: Age 18 years or older. Diagnosis of Uveitic macular edema (UME) or post-surgical macular edema (PSME). Can provide written informed consent prior to any study procedure being performed, able and willing to follow all instructions, and attend all study visits. UME of less than 3 years in duration or PSME of less than 1 year since diagnosis, with presence of intraretinal and/or subretinal fluid in the study eye, with CST of ≥ 320 µm by SD-OCT at baseline (as measured by the central reading center employing Heidelberg Spectralis spectral domain optical coherence tomography, SD-OCT). An ETDRS BCVA letter score ≤ 70 (Snellen 20/40) and ≥ 35 (Snellen 20/200) in the study eye at baseline (Visit 2). A documented diagnosis of inactive/stable uveitis (for UME) at the screening visit. A trial of topical NSAID or topical corticosteroids (for PSME) for at least one consecutive month but less than 3 consecutive months before screening visit with documented treatment failure on SD-OCT or based on investigator's clinical evaluation.
Exclusion Criteria: Subjects who meet any of the following exclusion criteria will not be included in the study. Macular edema considered to be due to a cause other than UME or PSME. An eye is not considered eligible if: (1) the macular edema is considered to be related to diabetes (2) clinical exam and/or OCT suggests that vitreoretinal interface abnormalities (eg, a taut posterior hyaloid or epiretinal membrane) are the primary cause of the macular edema, or (3) the macular edema is considered to be related to another condition such as age-related macular degeneration, retinal vein occlusion, or drug toxicity. A decrease in BCVA due to causes other than UME or PSME (eg, foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, previous vitreoretinal surgery, central serous retinopathy, non-retinal condition, substantial cataract, macular ischemia) that are likely to decrease BCVA by 3 lines or more (ie, cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal). Use of other ophthalmic formulations during the study. However, intraocular pressure (IOP) lowering eye drops are allowed if they become necessary due to increased IOP. History of glaucoma and documented glaucomatous optic neuropathy or clinically significant ocular hypertension in the opinion of the investigator, involving an IOP ≥25 mmHg on >3 anti-glaucoma medications in the study eye. Any other ocular disease that could cause substantial reduction in BCVA, including retinal detachment, epiretinal membrane, vitreous hemorrhage or fibrosis involving the macula in the study eye, other retinal inflammatory or infectious diseases. Active peri-ocular or ocular infection (eg, blepharitis, keratitis, scleritis, or conjunctivitis). History of infectious uveitis. High myopia (-8 diopter or more correction) in the study eye. Any form of diabetic retinopathy. History of increased intraocular pressure with topical steroid therapy. Pregnancy/breastfeeding. For UME: Active uveitis as determined by the presence of anterior chamber cells or vitreous cells. Unstable (increasing) dose of immunosuppressives during 2 months prior to the baseline visit. Immunosuppressives are defined as antimetabolites (methotrexate, mycophenolate mofetil, azathioprine, cyclosporine and tacrolimus, among others) and biologics (including adalimumab, infliximab, tocilizumab, golimumab, secukinumab and rituximab, and others). Treated with more than 2 types of immunosuppressives (excluding steroids) within 2 months prior to baseline visit. Unstable (increasing) dose of oral prednisone for 1 month before baseline visit. Oral prednisone therapy at dose >10 mg daily (or equivalent) within 1 month prior to baseline visit. History of contact lens use within 2 weeks prior to baseline or at any time during the study.
Information: leopardme@stanford.edu
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: 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: 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
