Study to Assess the Safety and Efficacy of OCU410 for Geographic Atrophy

Study Overview
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Brief Summary
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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). This is a multicenter study, which will be conducted in two phases and will enroll up to a total of 63 subjects.

Detailed Description
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Name of Sponsor/Company: Ocugen, Inc. 11 Great Valley Parkway Malvern, PA 19355 Name of Investigational Product: OCU410 Name of Active Ingredient: Adeno-associated viral vector 5 human RORA (AAV5-hRORA) Protocol Number: OCU410-101 Phase: 1/2 Country: US Title of Study: A Phase 1/2 Study to Assess the Safety and Efficacy of OCU410 for Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration. Study Center(s): Approximately five clinical study centers in the US. Background: Age-related Macular Degeneration (AMD) is an ocular disease where macular degenerative occurs. AMD manifests in two forms, Dry (nonexudative, atrophic) AMD and Wet (exudative, neovascular) AMD. Geographic atrophy (GA) is an advanced stage of dry AMD that affects nearly 1 million people in the US and 5 million people worldwide, with its prevalence increasing exponentially with age. It leads to progressive and irreversible loss of visual function due to the growth of atrophic lesions that destroy the retinal cells responsible for vision. OCU410 Product Information: Ocugen, Inc., has developed a proprietary modifier gene therapy platform, OCU410, as the second agent in a novel class of NHR-based gene modifier therapy for patients with dry AMD. The proposed indication for OCU410 (AAV5-hRORA) is for the treatment of GA secondary to dry AMD. The drug product is a sterile ophthalmic suspension for subretinal injection. OCU410 therapy regulates gene pathways contributing to GA by restoring homeostasis in the eye and thereby serving as a therapeutic candidate for dry AMD. The modifier gene therapy platform is a new way of addressing a genetic disease arising through a multitude of genetic mutations in various genes but leading to the same end result (phenotype) of a diseased condition. This study will be conducted in two phases enrolling up to 63 subjects. Treated subjects will receive a single subretinal injection of OCU410 in the study eye. Phase 1 is a multicenter, open-label, dose-ranging/dose-escalating study with a 3+3 design enrolling up to 18 subjects. Phase 2 is a randomized dose-expansion cohort in which 45 subjects will be randomized in a 1:1:1 ratio in to one of the 2 treatment arms or the untreated control arm.

Official Title
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A Phase 1/2 Study to Assess the Safety And Efficacy Of OCU410 For Geographic Atrophy Secondary To Dry Age-Related Macular Degeneration

Conditions
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Geographic Atrophy

Intervention / Treatment
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* Genetic: OCU410


Participation Criteria
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Eligibility Criteria
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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 one year. The history of any investigational product with a washout period of up to six 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 (i.e., pavingstone degeneration).

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Study will be conducted in 2 phases: Phase 1 will be 3+3 design will be used for sequential dose-escalation cohorts in which subjects will receive a single subretinal injection of OCU410 in the study eye. Phase 2 will be a dose-expansion phase of the study, where the subjects will be randomized in 1:1:1
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase1 Dose Escalation- Low Dose (2.5×10E10 vg/mL):<br>Low Dose (2.5×10E10 vg/mL): Subjects will receive a subretinal injection of OCU410 in the low dose concentration. | Genetic: OCU410<br>* Subretinal administration of OCU410<br>|
| Experimental: Phase1 Dose Escalation- Medium Dose (5×10E10 vg/mL):<br>Medium Dose (5×10E10 vg/mL): Subjects will receive a subretinal injection of OCU410 in the medium dose concentration. | Genetic: OCU410<br>* Subretinal administration of OCU410<br>|
| Experimental: Phase1 Dose Escalation- High Dose (1.5×10E11 vg/mL):<br>High Dose (1.5×10E11 vg/mL): Subjects will receive a subretinal injection in the high dose concentration. | Genetic: OCU410<br>* Subretinal administration of OCU410<br>|
| Experimental: Phase 2 Dose Expansion: Maximum tolerated dose (MTD) from Phase 1-Randomized Arm<br>Maximum tolerated dose (MTD) from Phase 1: Subjects will receive a subretinal injection in the MTD concentration. | Genetic: OCU410<br>* Subretinal administration of OCU410<br>|
| Experimental: Phase 2 Dose Expansion: Lower Dose from Phase 1-Randomized Arm<br>Subjects will receive a subretinal injection of OCU410 in a Lower Dose concentration. | Genetic: OCU410<br>* Subretinal administration of OCU410<br>|
| No Intervention: Control Arm<br>No Intervention Control Arm: Subject will not receive any active study intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in anatomy of ocular structures using Indirect ophthalmoscopy | We will use Indirect ophthalmoscopy to visualize the anatomy of ocular structures before and after sub-retinal injections and follow-up visits. | 12 months (Screening to 12 months post OCU410 administration) | 
| Change from baseline in BCVA (Best Corrected Visual Acuity) | Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. | 12 months (Screening to 12 months post OCU410 administration) | 
| Change in Low Luminance Visual Acuity | Measured by letter score. A higher score represents better vision | 12 months (Screening to 12 months post OCU410 administration) | 
| Change in the Intraocular Pressure (mmHg) | Measured by applanation or rebound tonometry with confirmation with Goldmann tonometer if IOP is outside normal range (8-21mmHg). | 12 months (Screening to 12 months post OCU410 administration) | 
| Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events)) | The primary endpoint is safety, determined by the number of ocular and non-ocular Study Drug-related adverse events (SDAE), treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). | 12 months (Screening to 12 months post OCU410 administration) | 
| Change in anatomy of ocular structures using Slit Lamp Biomicroscopy | We will use Slit-lamp Biomicroscopy to visualize the anatomy of ocular structures before and after sub-retinal injections and follow-up visits. | 12 months (Screening to 12 months post OCU410 administration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral and cellular immune response | Blood samples will be collected for the assessment. The secondary safety endpoints include change from baseline in Humoral and cellular immune response in response to OCU410 administration | 12 months (Screening to 12 months post OCU410 administration) | 
| Shedding of viral vector | Blood samples will be collected for the assessment to determine AAV vector shedding in systemic circulation after OCU410 administration | 12 months (Screening to 12 months post OCU410 administration) | 
| Laboratory parameters including serum chemistry and hematology | Blood samples will be collected for the assessment to determine a change from baseline after OCU410 administration. | 12 months (Screening to 12 months post OCU410 administration) |