Study to Assess the Safety and Efficacy of OCU410ST for Stargardt Disease

Phase 1

Recruiting

• Conditions: Stargardt Disease
• Interventions: Genetic: OCU410ST

• Registration Number: NCT05956626
• Lead Sponsor: Ocugen

Brief Summary

This is a Phase 1/2 Study to Assess the Safety and Efficacy of OCU410ST for Stargardt Disease.

This is a multicenter study, which will be conducted in two phases and will enroll up to a total of 42 subjects.

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 1/2 Study to Assess the Safety and Efficacy of OCU410ST for Stargardt Disease.

Study Center(s): Approximately five clinical 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.

This study will be conducted in two phases. enrolling up to 42.

Phase 1 is a multicenter, open-label, dose-ranging/dose escalation study with a 3+3 design enrolling up to 18 subjects

Phase 2 is a randomized, dose-expansion cohort in which 24 subjects will be randomized in a 1:1:1 ratio in to either one of two treatment groups (adults and pediatric subjects) or to an untreated (adults and pediatric subjects) control group.

Study Timeline

• Study First Submitted: 2023-06-30
• Study First Submitted QC: 2023-07-13
• Study First Posted: 2023-07-21
• Study Start: 2023-08-25
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-17
• Last Update Posted: 2025-03-20
• Primary Completion: 2025-10-28
• Study Completion: 2025-10-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

1. Are aged 18-65.
2. Have clinical evidence of a macular lesion phenotypically consistent with Stargardt Disease
3. The study eye should have at least one well-demarcated area of atrophy with a minimum diameter of 300 microns, and total lesion size <= 18 mmE2 and a BCVA of 50 ETDRS letters or better
4. Have confirmed presence of two pathogenic mutations in the ABCA4 gene
5. Have detectable outer nuclear layer (ONL) in the macular region tomography (SD-OCT).
6. Have BCVA of 50 letters or less (using ETDRS chart)

Key Inclusion Criteria for Pediatric Subjects:

1. Are aged 6-17.
2. Have clinical diagnosis of Stargardt Disease
3. The designated primary study eye must have at least one well-demarcated area of atrophy with a minimum diameter of 300 microns and a total lesion area <= 18 mmE2 and a BCVA of 35 ETDRS letters or better.
4. Have two (2) pathogenic mutations confirmed present, in the ABCA4 gene.

Key Exclusion Criteria for Adult Subjects:

1. Have previous treatment with a gene therapy or cell therapy product.
2. Have any concurrent retroviral therapy that would inactivate the investigational product.
3. Have any contradictions for subretinal injection and the use of anesthesia.
4. Have genes that mimic Stargardt Disease like ELOVL4, or PROM1.

Exclusion Criteria for Pediatric Subjects:

1. Have previous treatment with a gene therapy or cell therapy product.
2. Have any concurrent retroviral therapy that would inactivate the investigational product.
3. Have any intraocular surgery (including lens replacement surgery) within 6 months (prior to Screening), and any ophthalmic condition that may require surgery during the study period.
4. Have genes that mimic Stargardt Disease like ELOVL4, or PROM1.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Experimental: Phase1 Dose Escalation- High Dose (2.25×10E11 vg/mL):	OCU410ST	High Dose (2.25×10E11 vg/mL): Subjects will receive a subretinal injection of OCU410ST in the high dose concentration.
Experimental: Phase 2 Dose Expansion: Dose 2 from Phase 1-Randomized Pediatric Arm	OCU410ST	Subjects will receive a subretinal injection of OCU410ST with Lower Dose than Maximum tolerated dose (MTD) from Phase 1
Experimental: Phase 2 Dose Expansion: Dose 1 from Phase 1-Randomized Adult Arm	OCU410ST	Subjects will receive a subretinal injection of OCU410ST with Maximum tolerated dose (MTD) from Phase 1.
Experimental: Phase1 Dose Escalation- Low Dose (3.75×10E10 vg/mL):	OCU410ST	Low Dose (3.75×10E10 vg/mL): Subjects will receive a subretinal injection of 200 µL of OCU410ST in the low dose concentration.
Experimental: Phase1 Dose Escalation- Medium Dose (7.5×10E10 vg/mL):	OCU410ST	Medium Dose (7.5×10E10 vg/mL): Subjects will receive a subretinal injection of OCU410ST in the Medium dose concentration.
Experimental: Phase 2 Dose Expansion: Dose 1 from Phase 1-Randomized Pediatric Arm	OCU410ST	Subjects will receive a subretinal injection of OCU410ST with Maximum tolerated dose (MTD) from Phase 1.
Experimental: Phase 2 Dose Expansion: Dose 2 from Phase 1-Randomized Adult Arm	OCU410ST	Subjects will receive a subretinal injection of OCU410ST with Lower Dose than Maximum tolerated dose (MTD) from Phase 1

Primary Outcome Measures

Name	Time	Method
Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events))	12 months (Screening to 12 months post OCU410ST administration)	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).
Ophthalmic Safety: Change From Baseline in BCVA (Best Corrected Visual Acuity)	12 months (Screening to 12 months post OCU410ST administration)	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.
Ophthalmic Safety: Changes in Full Field ERG	12 months (Screening to 12 months post OCU410ST administration)	The International Society for Clinical Electrophysiology of Vision (ISCEV) guidelines will be followed for conducting ff-ERG (Full-field Electroretinography)
Ophthalmic Safety: Ophthalmoscope Measurements	12 months (Screening to 12 months post OCU410ST administration)	We will use Slit-lamp Biomicroscopy to visualize the anatomy of ocular structures before and after sub-retinal injections and follow-up visits.
Change Using Qualitative and quantitative assessments of autofluorescence pattern (FAF)	12 months (Screening to 12 months post OCU410ST administration)	Changes in the intensity of FAF will be evaluated from the baseline measurements, to assess the loss of retinal layers.
Ophthalmic Safety: Change in the Intraocular Pressure (mmHg)	12 months (Screening to 12 months post OCU410ST administration)	Measured by applanation or rebound tonometry with confirmation with Goldmann tonometer if IOP is outside normal range (8-21mmHg).

Secondary Outcome Measures

Name	Time	Method
Change in laboratory parameters for Hematology	12 months (Screening to 12 months post OCU410ST administration)	Blood samples will be collected to determine any significant change in hematology parameters including hematocrit, hemoglobin, red and white blood cell count, and any other parameters deemed necessary by study investigator from baseline after OCU410ST administration.
Humoral and cellular immune response	12 months (Screening to 12 months post OCU410ST administration)	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 OCU410ST administration
Change in laboratory parameters for Serum Chemistry	12 months (Screening to 12 months post OCU410ST administration)	Blood samples will be collected to determine any significant change in serum chemistry parameters including electrolytes, renal functions, liver functions, comprehensive metabolic panel and any other parameters deemed necessary by study investigator from baseline after OCU410ST administration.
Shedding of Viral Vector	12 months (Screening to 12 months post OCU410ST administration)	Blood samples will be collected for the assessment to determine AAV vector shedding in systemic circulation after OCU410ST administration

Trial Locations

Locations (6)

Mississippi Retina Associates; 🇺🇸 Jackson, Mississippi, United States

Retina Foundation of the Southwest; 🇺🇸 Dallas, Texas, United States

Bascom Palmer Eye Institute; 🇺🇸 Miami, Florida, United States

Associated Retina Consultants; 🇺🇸 Phoenix, Arizona, United States

Duke Eye Center; 🇺🇸 Durham, North Carolina, United States

Retina Consultants of Texas; 🇺🇸 Bellaire, Texas, United States