A Phase 2/3 Trial to Assess the Efficacy and Safety of OCU410ST for Stargardt Disease (GARDian3)

A PHASE 1 STUDY TO ASSESS THE SAFETY AND EFFICACY OF OCU410ST FOR STARGARDT DISEASE AND PHASE 2/3 PIVOTAL CONFIRMATORY CLINICAL TRIAL TO ASSESS THE SAFETY AND EFFICACY OF OCU410ST FOR STARGARDT DISEASE

Phase 2/3 Pivotal Confirmatory Clinical Trial is a randomized, outcome assessor-masked, multicenter study, that will enroll fifty-one (51) subjects. Subjects will be enrolled in a 2:1 ratio to either the treatment group (n=34 subjects) or to an untreated control group (n=17 subjects).

Phase 1 is complete and closed for enrollment. It was a multicenter, open-label, dose ranging/dose escalation study that enrolled 9 subjects.

OCU410ST Phase 1- Retinal Structure and Visual Function Data Results

• Safety: Favorable safety and tolerability profile No SAE deemed related to OCU410ST including intraocular inflammation, exudation, endophthalmitis, anterior ischemic optic neuropathy (AIONs) or vasculitis.
• Primary Endpoint: Structural Improvement Atrophic lesions grew slower by 48% at 12M in evaluable treated eyes when compared to untreated eyes
• Secondary Endpoint: Visual Function (BCVA) 100% evaluable treated eyes demonstrated stabilization or improvement when compared to untreated eyes in visual function

OCU410ST Phase 1- Structural and Functional Outcomes at 12M Data Results

• The GARDian3 clinical trial for ABCA4- related retinopathies including Stargardt disease builds upon encouraging results and positive data from the Phase 1 GARDian trial, which demonstrated 48% slower lesion growth at 12-month follow-up in evaluable treated eyes compared to untreated eyes
• Additionally, evaluable treated eyes showed a statistically significant (p=0.031) and clinically meaningful improvement of nearly 2-line/9-letter gain in best corrected visual acuity (BCVA) at 12-month follow-up when compared to untreated eyes.

Study Overview

• Status: Active, not recruiting
• Conditions: Stargardt Disease
• Intervention / Treatment: Drug: OCU410ST

Detailed Description

Name of Investigational Product: OCU410ST Name of Active Ingredient: Adeno-associated viral vector 5 human RORA (AAV5-hRORA)

Title of Study: A PHASE 1 STUDY TO ASSESS THE SAFETY AND EFFICACY OF OCU410ST FOR STARGARDT DISEASE AND PHASE 2/3 PIVOTAL CONFIRMATORY CLINICAL TRIAL TO ASSESS THE SAFETY AND EFFICACY OF OCU410ST FOR STARGARDT DISEASE

Study Center(s): Approximately fifteen study centers in the US.

Background: Stargardt disease is an eye disease that causes vision loss in children and young adults. It is an inherited disease caused by faulty genes that cause buildup of fat deposits in the eye. Currently, there is no approved treatment available for Stargardt disease.

OCU410ST Product Information:

OCU410ST is an Adeno-Associated Virus serotype 5 containing human RORA for the treatment of Stargardt disease. Dysregulation in lipid metabolism, oxidative stress, and anti-inflammatory mechanisms are critical for pathogenesis and progression of Stargardt disease. The role of hRORA in regulating these gene pathways strongly suggests OCU410ST could restore homeostasis in the eye and thereby serve as a therapeutic candidate for Stargardt disease.

Phase 2/3 Pivotal Confirmatory Clinical Trial is a randomized, outcome assessor-masked, multicenter study.

A total of fifty-one (51) subjects will be enrolled in a 2:1 ratio to either the treatment group (n=34 subjects) or to an untreated control group (n=17 subjects).

Treatment group: 34 subjects. Subjects will receive a single subretinal injection of 200 µL OCU410ST in concentration of 1.5×10E11 vg/mL.

Control group: 17 subjects. Subjects who are enrolled in the untreated control group of the study will not receive any treatment. They will be followed according to the same treatment schedule as the treated subjects.

Note: Data will be collected for the untreated eye at Screening, 4-month, 8-month, 12-month, four (4) long-term safety follow-up visits, and early termination visit (if applicable).

Data will be collected for the treated eye at Screening, treatment Day 1, Day 2, Day 15, 4-month, 8-month, 12-month, four (4) long-term safety follow-up visits, and early termination visit (if applicable).

Enrollment in the Phase 1 study is complete. Phase 1 enrolled a total of nine subjects in low, medium and high dose cohorts.

Low Dose Cohort (3.75×10E10 vg/mL):

Three (3) Subjects received a single subretinal injection of 200 µL OCU410ST in low dose concentration (3.75×10E10 vg/mL).

Medium Dose Cohort (7.5×10E10 vg/mL):

Three (3) Subjects received a single subretinal injection of 200 µL OCU410ST in medium dose concentration (7.5×10E10 vg/mL).

High Dose Cohort (2.25×10E11 vg/mL):

Three (3) Subjects received a single subretinal injection of 200 µL OCU410ST in high dose concentration (2.25×10E11 vg/mL).

• Study Type: Interventional
• Enrollment (Estimated): 51
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
  • California
    • Sacramento, California, United States, 95825
      • Retinal Consultants Medical Group
  • Florida
    • Gainesville, Florida, United States, 32607
      • Vitreo Retinal Associates, P.A.
    • Miami, Florida, United States, 33136
      • Bascom Palmer Eye Institute
    • Pompano Beach, Florida, United States, 33064
      • Advanced Research, LLC
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Retina Partners Midwest, P.C.
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Mississippi Retina Associates
  • Missouri
    • St Louis, Missouri, United States, 63128
      • The Retina Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Eye Center
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16505
      • Erie Retina Research, LLC
  • Texas
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas
    • Dallas, Texas, United States, 75231
      • Retina Foundation of the Southwest
    • McAllen, Texas, United States, 78503
      • Valley Retina Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Phase 2/3 Inclusion Criteria (applicable for both adult and pediatric subjects):

1. Males or females aged ≥5 years at the time of consent.
2. Subjects who have confirmed clinical and CLIA certified or equivalent genetic diagnosis of Stargardt disease (including ABCA4 related retinopathies).
3. Adult subjects who have BCVA of 75 letters or less in the study eye (20/32 Snellen equivalent) and Pediatric subjects who have a BCVA of 35 letters or better in the study eye (20/200 Snellen equivalent).
4. The study eye should have at least one well-demarcated area of atrophy with a minimum diameter of 300 microns, and total lesion size must add to less than or equal to ≤ 18 mm^2 (approximately 7-disc areas).
5. Have detectable outer nuclear layer (ONL) in the macular region

Phase 2/3 Exclusion Criteria (applicable for both adult and pediatric subjects):

1. Participation in ongoing antiretroviral therapy treatment.

2. Participation in any investigational therapy study or receipt of investigational treatment within 60 days prior to screening or 5 half-lives (whichever is longer).

   Any ophthalmic history of gene therapy, stem cell therapy, surgical implantation of prosthetic retinal chips, intravitreal or subretinal injections, or participation in an Alkeus ALK-001 study within the past 6 months.

3. Macular atrophy secondary to any disease other than Stargardt Disease (STGD).
4. Presence of genetic mutations that mimic Stargardt Disease like ELOVL4, or PROM1.
5. Contraindication to subretinal injection or use of anesthesia (local and/or general).

Phase 1 was a multicenter, open-label, dose-ranging/dose escalation study. Enrollment is complete for Phase 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2/3 Randomized Treatment Arm; Subjects will receive a single subretinal injection of 200uL OCU410ST in concentration of 1.5 x 10E11vg/mL	Drug: OCU410ST; Subretinal Administration of OCU410ST
No Intervention: Phase 2/3 Randomized Control Arm; Subjects will not receive any active study intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in atrophic lesion size as measured by Fundus Auto Fluorescence	Change in the area of atrophy will be evaluated from the baseline measurements, using FAF to assess the loss of retinal layers.	12 months (Screening to 12 months post OCU410ST administration)
Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events))	Safety will be 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 OCU410ST administration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Low Luminance Visual Acuity (LLVA)	Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Low Luminance Visual Acuity (LLVA) letter score. A higher score represents better vision.	12 months (Screening to 12 months post OCU410ST administration)
Change from baseline in Best Corrected Visual Acuity (BCVA)	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 OCU410ST administration)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients Global Impression of Change (PGIC) score	The Patients Global Impression of Change (PGIC) score will be administered to the patients to assess the impact of treatment on quality of subject's life.	12 months (Screening to 12 months post OCU410ST administration)
Care Giver Administered Global Impression of Change score	The Caregiver Global Impression of Change (GIC) will be administered to caregivers to evaluate the impact of treatment on the patient's quality of life.	12 months (Screening to 12 months post OCU410ST administration)

Collaborators and Investigators

• Sponsor: Ocugen
• Investigators: Study Director: Mahvish Tafseer, MD, MPH, Ocugen., Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2023
• Primary Completion (Estimated): September 28, 2026
• Study Completion (Estimated): September 28, 2026

Study Registration Dates

• First Submitted: June 30, 2023
• First Submitted That Met QC Criteria: July 13, 2023
• First Posted (Actual): July 21, 2023

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: ABCA4-associated retinopathies
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Stargardt Disease
• Other Study ID Numbers: OCU410ST-101/301; OCU410ST-101 (Other Identifier: Ocugen)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No