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

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

Study Description
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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.


Condition or disease Intervention/treatment Phase
Stargardt Disease Genetic: OCU410ST Phase 1 Phase 2

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 Design
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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

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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.
 Genetic: OCU410ST
Subretinal Administration of 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.
 Genetic: OCU410ST
Subretinal Administration of 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.
 Genetic: OCU410ST
Subretinal Administration of 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.
 Genetic: OCU410ST
Subretinal Administration of 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.
 Genetic: OCU410ST
Subretinal Administration of 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
 Genetic: OCU410ST
Subretinal Administration of 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
 Genetic: OCU410ST
Subretinal Administration of 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


Outcome Measures
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Primary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.

  4. 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).

  5. 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.

  6. 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)


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.

  4. 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.


Other Outcome Measures:
  1. 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)

  2. 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.


Eligibility Criteria
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Information from the National Library of Medicine

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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
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.
Contacts and Locations
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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


Contacts
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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

Locations
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United States, Arizona
Associated Retina Consultants Recruiting
Phoenix, Arizona, United States, 85020
Contact: Erin Fox    480-999-5458    erin.fox@doctrials.com   
Contact: Mallory Mintert    480-999-5458    Mallory.mintert@doctrials.com   
Principal Investigator: Benjamin Bakall, M.D; Ph.D         
United States, Florida
Bascom Palmer Eye Institute Not yet recruiting
Miami, Florida, United States, 33136
Contact: Adriana Padilla, FMD, CCRP    305-482-4292    apd86@med.miami.edu   
Principal Investigator: Lam Byron, MD         
United States, Mississippi
Mississippi Retina Associates Recruiting
Jackson, Mississippi, United States, 39202
Contact: Anne Britt, MHA, CCRC    601-981-4091 ext 646    abritt@msretina.com   
Contact: Mallie Taylor    803-767-0705    mtaylor@retinaconsultantsofamerica.com   
Principal Investigator: Michael J Borne, MD         
United States, North Carolina
Duke Eye Center Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Lyndsay Lawter    919-681-9459    Lyndsay Lawter <lyndsay.lawter@duke.edu>   
Contact: Sarah Jones, MS, CRCC    919-681-6584    sarah.jones1@duke.edu   
Principal Investigator: Ramiro Maldonado, MD         
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         
Sponsors and Collaborators
Ocugen
Investigators
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Study Director: Murthy Chavali, Ph.D Ocugen., Inc.
More Information
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Responsible Party: Ocugen
ClinicalTrials.gov Identifier: NCT05956626    
Other Study ID Numbers: OCU410ST-101
First Posted: July 21, 2023    Key Record Dates
Last Update Posted: March 12, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Stargardt Disease
Macular Degeneration
Eye Diseases, Hereditary
Eye Diseases
 Retinal Degeneration
Retinal Diseases
Genetic Diseases, Inborn