Clinical trial NCT06018558: Study to Assess the Safety and Efficacy of OCU410 for Geographic Atrophy
Official title: A Phase 1/2 Study to Assess the Safety And Efficacy Of OCU410 For Geographic Atrophy Secondary To Dry Age-Related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Geographic Atrophy
Lead sponsor: Ocugen
Sponsor class: INDUSTRY
First posted: 2023-08-30
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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 is a dose-expansion phase of the study, where up to 51 subjects will be randomized in 1:1:1 ratio to either two OCU410 dose groups (n=17 per group) or to an untreated control group (n=17).
Primary purpose: TREATMENT

Brief summary: 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 60 subjects.

Detailed 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 14 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 60 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 9 subjects.

Phase 2 is a dose-expansion phase of the study, where up to 51 subjects will be randomized in 1:1:1 ratio to either two OCU410 dose groups (n=17 per group) or to an untreated control group (n=17).

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Eligibility criteria: 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. Subjects can receive an approved drug for AMD in the fellow eye, if required.

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.

Primary outcomes:
measure: Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events))
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
measure: Change in anatomy of ocular structures using Slit Lamp Biomicroscopy
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
measure: Change in anatomy of ocular structures using Indirect ophthalmoscopy
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
measure: Change from baseline in BCVA (Best Corrected Visual Acuity)
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
measure: Change in Low Luminance Visual Acuity
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
measure: Change in the Intraocular Pressure (mmHg)
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
Secondary outcomes:
measure: Humoral and cellular immune response
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
measure: Shedding of viral vector
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
measure: Laboratory parameters including serum chemistry and hematology
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
Other outcomes:
measure: Structural Outcome: Change Using Qualitative and quantitative assessments of autofluorescence pattern (FAF)
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
measure: Changes in National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ25)
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
measure: Change From Baseline in Mean Threshold Sensitivity (MAIA)
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
measure: Change from Baseline in drusen volume using SD-OCT
timeFrame: 12 months (Screening to 12 months post OCU410 administration)
Locations:
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Coral Springs
country: United States
facility: Advanced Research, LLC
state: Florida
city: Carmel
country: United States
facility: Miidwest Eye Institute
state: Indiana
city: Jackson
country: United States
facility: Mississippi Retina Associates
state: Mississippi
city: Saint Louis
country: United States
facility: The Retina Institute
state: Missouri
city: Cherry Hill
country: United States
facility: Mid Atlantic Retina
state: New Jersey
city: Durham
country: United States
facility: Duke Eye Center
state: North Carolina
city: Pittsburgh
country: United States
facility: The University of Pittsburgh
state: Pennsylvania
city: Bellaire
country: United States
facility: B) Retina Consultants of Texas
state: Texas
city: Dallas
country: United States
facility: A) Retina Foundation of the Southwest
state: Texas
city: McAllen
country: United States
facility: Valley retina Institute
state: Texas
city: La Crosse
country: United States
facility: Gundersen Health System
state: Wisconsin
Study officials:
affiliation: Ocugen
name: Murthy Chavali, Ph.D
role: STUDY_DIRECTOR
References: