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

Stargardt Disease Clinical Trial

— GARDian  

Official title:

A Phase 1/2 Study to Assess the Safety and Efficacy of OCU410ST for STARGARDT DISEASE

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05956626
• Other study ID #: OCU410ST-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 25, 2023
• Est. completion date: October 28, 2025

Study information

• Verified date: March 2024
• Source: Ocugen
• Contact: Umair Qazi, MD, MPH
• Phone: +1 (202)-817-0787
• Email: umair.qazi[@]ocugen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: October 28, 2025
• Est. primary completion date: October 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Macular Degeneration
• Stargardt Disease

Intervention

Genetic:
• OCU410ST
Subretinal Administration of OCU410ST

Locations

Country	Name	City	State
United States	Retina Consultants of Texas	Bellaire	Texas
United States	Retina Foundation of the Southwest	Dallas	Texas
United States	Duke Eye Center	Durham	North Carolina
United States	Mississippi Retina Associates	Jackson	Mississippi
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	Associated Retina Consultants	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Ocugen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in macular thickness on Spectra Domain Optical Coherence Tomography (SD-OCT)	The change in the macular thickness will be Measured by spectral domain optical coherence tomography (SD-OCT)	12 months (Screening to 12 months post OCU410ST administration)
Other	Change in Quality-of-life measure using NEI VFQ-25 (Adult subjects only)	The National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ25) questionnaires will be administered to assess the impact of vision on quality of subject's life.	12 months (Screening to 12 months post OCU410ST administration)
Primary	Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events))	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).	12 months (Screening to 12 months post OCU410ST administration)
Primary	Ophthalmic Safety: Change From Baseline in BCVA (Best Corrected Visual Acuity)	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)
Primary	Ophthalmic Safety: Ophthalmoscope Measurements	We will use Slit-lamp Biomicroscopy to visualize the anatomy of ocular structures before and after sub-retinal injections and follow-up visits.	12 months (Screening to 12 months post OCU410ST administration)
Primary	Ophthalmic Safety: Change in the Intraocular Pressure (mmHg)	Measured by applanation or rebound tonometry with confirmation with Goldmann tonometer if IOP is outside normal range (8-21mmHg).	12 months (Screening to 12 months post OCU410ST administration)
Primary	Change Using Qualitative and quantitative assessments of autofluorescence pattern (FAF)	Changes in the intensity of FAF will be evaluated from the baseline measurements, to assess the loss of retinal layers.	12 months (Screening to 12 months post OCU410ST administration)
Primary	Ophthalmic Safety: Changes in Full Field ERG	The International Society for Clinical Electrophysiology of Vision (ISCEV) guidelines will be followed for conducting ff-ERG (Full-field Electroretinography)	12 months (Screening to 12 months post OCU410ST administration)
Secondary	Humoral and cellular immune response	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	12 months (Screening to 12 months post OCU410ST administration)
Secondary	Shedding of Viral Vector	Blood samples will be collected for the assessment to determine AAV vector shedding in systemic circulation after OCU410ST administration	12 months (Screening to 12 months post OCU410ST administration)
Secondary	Change in laboratory parameters for Hematology	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.	12 months (Screening to 12 months post OCU410ST administration)
Secondary	Change in laboratory parameters for Serum Chemistry	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.	12 months (Screening to 12 months post OCU410ST administration)