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

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.

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.

Eligibility Criteria:
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.