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

• ClinicalTrials.gov Identifier: NCT05956626
• Recruitment Status: Recruiting
• First Posted: July 21, 2023
• Last Update Posted: March 12, 2024
• Sponsor: Ocugen
• Information provided by (Responsible Party): Ocugen

Tracking Information

• First Submitted Date: June 30, 2023
• First Posted Date: July 21, 2023
• Last Update Posted Date: March 12, 2024
• Actual Study Start Date: August 25, 2023
• Estimated Primary Completion Date: October 28, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 6, 2023)

• Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events)) [ Time Frame: 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) [ Time Frame: 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: Ophthalmoscope Measurements [ Time Frame: 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.
• Ophthalmic Safety: Change in the Intraocular Pressure (mmHg) [ Time Frame: 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).
• Change Using Qualitative and quantitative assessments of autofluorescence pattern (FAF) [ Time Frame: 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: Changes in Full Field ERG [ Time Frame: 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)

Original Primary Outcome Measures (submitted: July 13, 2023)

• Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events)) [ Time Frame: 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). SDAEs are considered the primary adverse event of interest and defined as AEs and SAEs that are direct subjects to the Study Drug only. AEs will be defined as Ocular or Non-ocular for presentation. TEAE are defined as an event that was not present prior to administration of the dose of study drug and present after the dose, or if it represents the exacerbation of an event that was present prior to the dose. TEAEs are determined by the investigator, and given a gradient on how they are related to the specific treatment, such as surgery, cortical steroid etc. SAEs are defined as counts, frequencies and percentages of SAEs including Resulted in Death, Life-threatening, Hospitalization, Disabling/incapacitating, Congenital anomaly or birth defect and Medically significant AEs
• Ophthalmic Safety: Change From Baseline in BCVA (Best Corrected Visual Acuity) [ Time Frame: 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: Ophthalmoscope Measurements [ Time Frame: 12 months (Screening to 12 months post OCU410ST administration) ]
  We will use Slit-lamp biomicroscopy and Indirect ophthalmoscopy to visualize the anatomy of ocular structures before and after sub-retinal injections and follow-up visits. These measurements will allow documentation of abnormalities in the retina as well as the optic nerve, vessels and macula lutea post-study drug administration If visual acuity is so poor that the participant is unable to count fingers or perceive hand motion, light perception will be tested with the indirect ophthalmoscope as the light source.
• Ophthalmic Safety: Change in the Intraocular Pressure (mmHg) [ Time Frame: 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).
• Change Using Qualitative and quantitative assessments of autofluorescence pattern (FAF) [ Time Frame: 12 months (Screening to 12 months post OCU410ST administration) ]
  The intensity of FAF will be evaluated using 55° posterior pole scanning.
• Ophthalmic Safety: Changes in Full Field ERG [ Time Frame: 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), plus an S-Cone protocol with blue flash on amber background.

Current Secondary Outcome Measures (submitted: September 6, 2023)

• Humoral and cellular immune response [ Time Frame: 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
• Shedding of Viral Vector [ Time Frame: 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
• Change in laboratory parameters for Hematology [ Time Frame: 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.
• Change in laboratory parameters for Serum Chemistry [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: July 13, 2023)

• Humoral and cellular immune response [ Time Frame: 12 months (Screening to 12 months post OCU410ST administration) ]
  Blood samples will be collected for the assessment. These samples will be analyzed using validated assays at a bioanalytical laboratory. The secondary safety endpoints include change from baseline in Humoral and cellular immune response using anti-AAV5 antibodies, T-cell response to OCU410 administration
• Shedding of Viral Vector [ Time Frame: 12 months (Screening to 12 months post OCU410ST administration) ]
  Blood samples will be collected for the assessment. These samples will be analyzed using validated assays at a bioanalytical laboratory. The secondary safety endpoints include change from baseline to determine AAV vector shedding in systemic circulation after OCU410 administration
• Laboratory parameters including serum chemistry and hematology [ Time Frame: 12 months (Screening to 12 months post OCU410 administration) ]
  Blood samples will be collected for the assessment. These samples will be analyzed using validated assays at a bioanalytical laboratory. The secondary safety endpoints include change from baseline after OCU410 administration.

Current Other Pre-specified Outcome Measures (submitted: September 6, 2023)

• Changes in macular thickness on Spectra Domain Optical Coherence Tomography (SD-OCT) [ Time Frame: 12 months (Screening to 12 months post OCU410ST administration) ]
  The change in the macular thickness will be Measured by spectral domain optical coherence tomography (SD-OCT)
• Change in Quality-of-life measure using NEI VFQ-25 (Adult subjects only) [ Time Frame: 12 months (Screening to 12 months post OCU410ST administration) ]
  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.

Original Other Pre-specified Outcome Measures (submitted: July 13, 2023)

• Structural Outcome: Change Using Qualitative and quantitative assessments of autofluorescence pattern (FAF) [ Time Frame: 12 months (Screening to 12 months post OCU410ST administration) ]
  The intensity of FAF will be evaluated using 55° posterior pole scanning and atrophic lesion size will be measured in mm2
• Change From Baseline in Best Corrected Visual Acuity (BCVA) [ Time Frame: 12 months (Screening to 12 months post OCU410ST administration) ]
  Change in ETDRS (Early Treatment of Diabetic Retinopathy) Letter Score. Minimum value=0; Maximum value=100. Higher scores indicate better visual acuity. Change = 12 Mo value - Baseline value
• Changes in macular thickness on Spectra Domain Optical Coherence Tomography (SD-OCT) [ Time Frame: 12 months (Screening to 12 months post OCU410ST administration) ]
  The change in the macular thickness will be Measured by spectral domain optical coherence tomography (SD-OCT) and assessed by a central reading center.
• Change in Quality-of-life measure using NEI VFQ-25 (Adult subjects only) [ Time Frame: 12 months (Screening to 12 months post OCU410ST administration) ]
  The National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ25) and the Michigan Retinal Degeneration Questionnaire (MRDQ) questionnaires will be administered to assess the impact of vision on quality of subject's life.

Descriptive Information

• Brief Title: 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

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 Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
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.

Masking: Single (Outcomes Assessor)
Masking Description:

The following team members will be masked:

Bio-Statistician, Data Programmer, Imaging Reading Center Team, Head of Clinical Development and Medical Affairs.

Primary Purpose: Treatment

• Condition: Stargardt Disease

Intervention

Genetic: OCU410ST

Subretinal Administration of OCU410ST

Study Arms

• Experimental: Experimental: Phase1 Dose Escalation- Low Dose (3.75×10E10 vg/mL):
  Low Dose (3.75×10E10 vg/mL): Subjects will receive a subretinal injection of 200 µL of OCU410ST in the low dose concentration.
  Intervention: Genetic: OCU410ST
• Experimental: Experimental: Phase1 Dose Escalation- Medium Dose (7.5×10E10 vg/mL):
  Medium Dose (7.5×10E10 vg/mL): Subjects will receive a subretinal injection of OCU410ST in the Medium dose concentration.
  Intervention: Genetic: OCU410ST
• Experimental: Experimental: Phase1 Dose Escalation- High Dose (2.25×10E11 vg/mL):
  High Dose (2.25×10E11 vg/mL): Subjects will receive a subretinal injection of OCU410ST in the high dose concentration.
  Intervention: Genetic: OCU410ST
• Experimental: Experimental: Phase 2 Dose Expansion: Dose 1 from Phase 1-Randomized Adult Arm
  Subjects will receive a subretinal injection of OCU410ST with Maximum tolerated dose (MTD) from Phase 1.
  Intervention: Genetic: OCU410ST
• Experimental: Experimental: Phase 2 Dose Expansion: Dose 1 from Phase 1-Randomized Pediatric Arm
  Subjects will receive a subretinal injection of OCU410ST with Maximum tolerated dose (MTD) from Phase 1.
  Intervention: Genetic: OCU410ST
• Experimental: Experimental: Phase 2 Dose Expansion: Dose 2 from Phase 1-Randomized Adult Arm
  Subjects will receive a subretinal injection of OCU410ST with Lower Dose than Maximum tolerated dose (MTD) from Phase 1
  Intervention: Genetic: OCU410ST
• Experimental: Experimental: Phase 2 Dose Expansion: Dose 2 from Phase 1-Randomized Pediatric Arm
  Subjects will receive a subretinal injection of OCU410ST with Lower Dose than Maximum tolerated dose (MTD) from Phase 1
  Intervention: Genetic: OCU410ST
• No Intervention: No Intervention- Randomized Control Adult Arm
  No Intervention Control Arm: Subject will not receive any active study intervention
• No Intervention: No Intervention- Randomized Control Pediatric Arm
  No Intervention Control Arm: Subject will not receive any active study intervention

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 13, 2023): 42
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 28, 2025
• Estimated Primary Completion Date: October 28, 2025 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes

• Ages: 6 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Umair Qazi, MD, MPH; +1 (202)-817-0787; umair.qazi@ocugen.com

Contact: Mahvish Tafseer, MD, ACRP-CP; +1 (215) 934-8891; mahvish.tafseer@ocugen.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05956626
• Other Study ID Numbers: OCU410ST-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ocugen
• Original Responsible Party: Same as current
• Current Study Sponsor: Ocugen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Murthy Chavali, Ph.D; Ocugen., Inc.

• PRS Account: Ocugen
• Verification Date: March 2024