Study to Assess the Safety and Efficacy of OCU410ST for Stargardt Disease (GARDian)
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| ClinicalTrials.gov Identifier: NCT05956626 |
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Recruitment Status :
Recruiting
First Posted : July 21, 2023
Last Update Posted : October 25, 2023
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Stargardt Disease | Genetic: OCU410ST | Phase 1 Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 42 participants |
| 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 |
| Official Title: | A Phase 1/2 Study to Assess the Safety and Efficacy of OCU410ST for STARGARDT DISEASE |
| Actual Study Start Date : | August 25, 2023 |
| Estimated Primary Completion Date : | October 28, 2025 |
| Estimated Study Completion Date : | October 28, 2025 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Genetic: OCU410ST
Subretinal Administration of OCU410ST |
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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.
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Genetic: OCU410ST
Subretinal Administration of OCU410ST |
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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.
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Genetic: OCU410ST
Subretinal Administration of OCU410ST |
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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.
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Genetic: OCU410ST
Subretinal Administration of OCU410ST |
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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.
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Genetic: OCU410ST
Subretinal Administration of OCU410ST |
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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
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Genetic: OCU410ST
Subretinal Administration of OCU410ST |
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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
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Genetic: OCU410ST
Subretinal Administration of OCU410ST |
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No Intervention: No Intervention- Randomized Control Adult Arm
No Intervention Control Arm: Subject will not receive any active study intervention
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No Intervention: No Intervention- Randomized Control Pediatric Arm
No Intervention Control Arm: Subject will not receive any active study intervention
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- 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)
- 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.
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 6 Years to 65 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Gender Based Eligibility: | Yes |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Are aged 18-65.
- Have clinical evidence of a macular lesion phenotypically consistent with Stargardt Disease
- 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
- Have confirmed presence of two pathogenic mutations in the ABCA4 gene
- Have detectable outer nuclear layer (ONL) in the macular region tomography (SD-OCT).
- Have BCVA of 50 letters or less (using ETDRS chart)
Key Inclusion Criteria for Pediatric Subjects:
- Are aged 6-17.
- Have clinical diagnosis of Stargardt Disease
- 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.
- Have two (2) pathogenic mutations confirmed present, in the ABCA4 gene.
Key Exclusion Criteria for Adult Subjects:
- Have previous treatment with a gene therapy or cell therapy product.
- Have any concurrent retroviral therapy that would inactivate the investigational product.
- Have any contradictions for subretinal injection and the use of anesthesia.
- Have genes that mimic Stargardt Disease like ELOVL4, or PROM1.
Exclusion Criteria for Pediatric Subjects:
- Have previous treatment with a gene therapy or cell therapy product.
- Have any concurrent retroviral therapy that would inactivate the investigational product.
- 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.
- Have genes that mimic Stargardt Disease like ELOVL4, or PROM1.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05956626
| 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 |
| United States, Texas | |
| Retina Consultants of Texas | Recruiting |
| Bellaire, Texas, United States, 77401 | |
| Contact: Rebbecca Tiang 800-833-5921 rebbecca.taing@retinaconsultantstexas.com | |
| Principal Investigator: Charles Wykoff, MD, PhD | |
| Retina Foundation of the Southwest | Recruiting |
| Dallas, Texas, United States, 75231 | |
| Contact: Kimberly Cummings, CCRC 214-363-3911 ext 128 evasquez@retinafoundation.org | |
| Principal Investigator: Karl Csaky, MD, PhD | |
| Study Director: | Huma Qamar, MD, MPH, CMI | Ocugen., Inc. |
| Responsible Party: | Ocugen |
| ClinicalTrials.gov Identifier: | NCT05956626 |
| Other Study ID Numbers: |
OCU410ST-101 |
| First Posted: | July 21, 2023 Key Record Dates |
| Last Update Posted: | October 25, 2023 |
| Last Verified: | October 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Stargardt Disease Macular Degeneration Eye Diseases, Hereditary Eye Diseases |
Retinal Degeneration Retinal Diseases Genetic Diseases, Inborn |