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

Ocugen

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Geographic Atrophy

Treatments: Genetic: OCU410

Study type: Interventional

Funder types: Industry

Identifiers

NCT06018558

OCU410-101

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 63 estimated patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subjects 50 years of age or older.

2. BCVA of approximately 21 letters or more using Early Treatment Diabetic Retinopathy Study (ETDRS) chart (20/320 Snellen equivalent).

3. Fundus autofluorescence (FAF) imaging shows:

   1. Total GA area ≥2.0 and ≤20.5 mm2 (1 and 8 disk areas [DA], respectively)
   2. 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 above in 3.a
   3. 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
   4. Presence of any pattern of hyper-autofluorescence in the junctional zone of GA

4. Subjects who had prior treatment with an approved drug for AMD, e.g. Izerway® (Avacincaptad pegol) or Syfovre® (Pegcetacoplan injection) can be included, after a washout period of at least 3 months in study eye or fellow eye

Exclusion criteria

1. Previous treatment with a gene-therapy or cell therapy product
2. 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).
3. Spherical equivalent of the refractive error demonstrating > 6 diopters of myopia or an axial length >26 mm, inability to fixate, uncontrolled glaucoma, advanced cataract, corneal abnormalities, medium haze, and other retinal pathologies.
4. Any history or current evidence of exudative ("wet") AMD including any evidence of retinal pigment epithelium rips, branch retinal artery or vein occlusion, corneal transplant, or evidence of neovascularization anywhere in the retina based on fluorescein angiogram.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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63 participants in 6 patient groups

Phase1 Dose Escalation- Low Dose (2.5×10E10 vg/mL):

Experimental group

Description:

Low Dose (2.5×10E10 vg/mL): Subjects will receive a subretinal injection of OCU410 in the low dose concentration.

Treatment:

Genetic: OCU410

Phase1 Dose Escalation- Medium Dose (5×10E10 vg/mL):

Experimental group

Description:

Medium Dose (5×10E10 vg/mL): Subjects will receive a subretinal injection of OCU410 in the medium dose concentration.

Treatment:

Genetic: OCU410

Phase1 Dose Escalation- High Dose (1.5×10E11 vg/mL):

Experimental group

Description:

High Dose (1.5×10E11 vg/mL): Subjects will receive a subretinal injection in the high dose concentration.

Treatment:

Genetic: OCU410

Phase 2 Dose Expansion: Maximum tolerated dose (MTD) from Phase 1-Randomized Arm

Experimental group

Description:

Maximum tolerated dose (MTD) from Phase 1: Subjects will receive a subretinal injection in the MTD concentration.

Treatment:

Genetic: OCU410

Phase 2 Dose Expansion: Lower Dose from Phase 1-Randomized Arm

Experimental group

Description:

Subjects will receive a subretinal injection of OCU410 in a Lower Dose concentration.

Treatment:

Genetic: OCU410

Control Arm

No Intervention group

Description:

No Intervention Control Arm: Subject will not receive any active study intervention