Clinical trial NCT05956626: Study to Assess the Safety and Efficacy of OCU410ST for Stargardt Disease
Official title: A Phase 1/2 Study to Assess the Safety and Efficacy of OCU410ST for STARGARDT DISEASE
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Stargardt Disease
Lead sponsor: Ocugen
Sponsor class: INDUSTRY
First posted: 2023-07-21
Enrollment: 42
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study will be conducted in two phases.

Phase 1 is a multicenter, open-label, dose-ranging/dose escalation study. A 3+3 study design will be used for the sequential dose-escalation cohorts in which subjects will receive a single subretinal injection of OCU410ST.

Phase 2 is a dose-expansion phase of the study, where the subjects will be randomized in a 1:1:1 ratio to either one of two treatment groups (adult and pediatric subjects) or to an untreated (adult and pediatric subjects) control group.
Primary purpose: TREATMENT

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.

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.

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 OCU410ST administration)
measure: Ophthalmic Safety: Change From Baseline in BCVA (Best Corrected Visual Acuity)
timeFrame: 12 months (Screening to 12 months post OCU410ST administration)
measure: Ophthalmic Safety: Ophthalmoscope Measurements
timeFrame: 12 months (Screening to 12 months post OCU410ST administration)
measure: Ophthalmic Safety: Change in the Intraocular Pressure (mmHg)
timeFrame: 12 months (Screening to 12 months post OCU410ST administration)
measure: Change Using Qualitative and quantitative assessments of autofluorescence pattern (FAF)
timeFrame: 12 months (Screening to 12 months post OCU410ST administration)
measure: Ophthalmic Safety: Changes in Full Field ERG
timeFrame: 12 months (Screening to 12 months post OCU410ST administration)
Secondary outcomes:
measure: Humoral and cellular immune response
timeFrame: 12 months (Screening to 12 months post OCU410ST administration)
measure: Shedding of Viral Vector
timeFrame: 12 months (Screening to 12 months post OCU410ST administration)
measure: Change in laboratory parameters for Hematology
timeFrame: 12 months (Screening to 12 months post OCU410ST administration)
measure: Change in laboratory parameters for Serum Chemistry
timeFrame: 12 months (Screening to 12 months post OCU410ST administration)
Other outcomes:
measure: Changes in macular thickness on Spectra Domain Optical Coherence Tomography (SD-OCT)
timeFrame: 12 months (Screening to 12 months post OCU410ST administration)
measure: Change in Quality-of-life measure using NEI VFQ-25 (Adult subjects only)
timeFrame: 12 months (Screening to 12 months post OCU410ST administration)
Locations:
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Jackson
country: United States
facility: Mississippi Retina Associates
state: Mississippi
city: Durham
country: United States
facility: Duke Eye Center
state: North Carolina
city: Bellaire
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Dallas
country: United States
facility: Retina Foundation of the Southwest
state: Texas
Study officials:
affiliation: Ocugen., Inc.
name: Murthy Chavali, Ph.D
role: STUDY_DIRECTOR
References: