Study to Assess the Safety and Efficacy of OCU410 for Geographic Atrophy (ArMaDa)

March 7, 2024 updated by: Ocugen

A Phase 1/2 Study to Assess the Safety And Efficacy Of OCU410 For Geographic Atrophy Secondary To Dry Age-Related Macular Degeneration

This is a Phase 1/2 Study to Assess the Safety and Efficacy of OCU410 for Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration (AMD).

This is a multicenter study, which will be conducted in two phases and will enroll up to a total of 63 subjects.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Name of Sponsor/Company:

Ocugen, Inc. 11 Great Valley Parkway Malvern, PA 19355

Name of Investigational Product: OCU410

Name of Active Ingredient:

Adeno-associated viral vector 5 human RORA (AAV5-hRORA) Protocol Number: OCU410-101 Phase: 1/2 Country: US

Title of Study:

A Phase 1/2 Study to Assess the Safety and Efficacy of OCU410 for Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration.

Study Center(s): Approximately five clinical study centers in the US.

Background:

Age-related Macular Degeneration (AMD) is an ocular disease where macular degenerative occurs. AMD manifests in two forms, Dry (nonexudative, atrophic) AMD and Wet (exudative, neovascular) AMD. Geographic atrophy (GA) is an advanced stage of dry AMD that affects nearly 1 million people in the US and 5 million people worldwide, with its prevalence increasing exponentially with age. It leads to progressive and irreversible loss of visual function due to the growth of atrophic lesions that destroy the retinal cells responsible for vision.

OCU410 Product Information:

Ocugen, Inc., has developed a proprietary modifier gene therapy platform, OCU410, as the second agent in a novel class of NHR-based gene modifier therapy for patients with dry AMD. The proposed indication for OCU410 (AAV5-hRORA) is for the treatment of GA secondary to dry AMD. The drug product is a sterile ophthalmic suspension for subretinal injection. OCU410 therapy regulates gene pathways contributing to GA by restoring homeostasis in the eye and thereby serving as a therapeutic candidate for dry AMD. The modifier gene therapy platform is a new way of addressing a genetic disease arising through a multitude of genetic mutations in various genes but leading to the same end result (phenotype) of a diseased condition.

This study will be conducted in two phases enrolling up to 63 subjects. Treated subjects will receive a single subretinal injection of OCU410 in the study eye.

Phase 1 is a multicenter, open-label, dose-ranging/dose-escalating study with a 3+3 design enrolling up to 18 subjects.

Phase 2 is a randomized dose-expansion cohort in which 45 subjects will be randomized in a 1:1:1 ratio in to one of the 2 treatment arms or the untreated control arm.

Study Type

Interventional

Enrollment (Estimated)

63

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85020
        • Recruiting
        • Associated Retina Consultants
        • Contact:
        • Contact:
        • Principal Investigator:
          • Benjamin Bakall, M.D; Ph.D
    • Mississippi
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke Eye Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Majda Hadziahmetovic, M.D
    • Texas
      • Bellaire, Texas, United States, 77401
      • Dallas, Texas, United States, 75231
        • Recruiting
        • A) Retina Foundation of the Southwest
        • Contact:
        • Principal Investigator:
          • Karl Csaky, M.D; Ph.D
    • Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Subjects 50 years of age or older.
  2. BCVA of approximately 24 letters or more using Early Treatment Diabetic Retinopathy Study (ETDRS) chart (20/320 Snellen equivalent).

  3. Fundus autofluorescence (FAF) imaging shows:

    1. Total GA area ≥2.5 and ≤17.5 mm2 (1 and 7 disk areas [DA], respectively)
    2. If GA is multifocal, at least one focal lesion must be ≥1.25 mm2 (0.5 DA), with the overall aggregate area of GA as specified above in 3.a
    3. The entire GA lesion must be completely visualized on the macula-centered image and must be able to be imaged in its entirety, and not contiguous with any areas of peripapillary atrophy
    4. Presence of any pattern of hyper-autofluorescence in the junctional zone of GA
  4. Subjects who had prior treatment with an approved drug for AMD, e.g. Izerway® (Avacincaptad pegol) or Syfovre® (Pegcetacoplan injection) can be included, after a washout period of at least 3 months in study eye or fellow eye

Exclusion Criteria:

  1. Previous treatment with a gene-therapy or cell therapy product
  2. GA due to causes other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like Plaquenil maculopathy. However, benign conditions of the vitreous or peripheral retina are not exclusionary (i.e., pavingstone degeneration).
  3. Spherical equivalent of the refractive error demonstrating > 6 diopters of myopia or an axial length >26 mm, inability to fixate, uncontrolled glaucoma, advanced cataract, corneal abnormalities, medium haze, and other retinal pathologies.
  4. Any history or current evidence of exudative ("wet") AMD including any evidence of retinal pigment epithelium rips, branch retinal artery or vein occlusion, corneal transplant, or evidence of neovascularization anywhere in the retina based on fluorescein angiogram.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase1 Dose Escalation- Low Dose (2.5×10E10 vg/mL):
Low Dose (2.5×10E10 vg/mL): Subjects will receive a subretinal injection of OCU410 in the low dose concentration.
Genetic: OCU410
Subretinal administration of OCU410
Experimental: Phase1 Dose Escalation- Medium Dose (5×10E10 vg/mL):
Medium Dose (5×10E10 vg/mL): Subjects will receive a subretinal injection of OCU410 in the medium dose concentration.
Genetic: OCU410
Subretinal administration of OCU410
Experimental: Phase1 Dose Escalation- High Dose (1.5×10E11 vg/mL):
High Dose (1.5×10E11 vg/mL): Subjects will receive a subretinal injection in the high dose concentration.
Genetic: OCU410
Subretinal administration of OCU410
Experimental: Phase 2 Dose Expansion: Maximum tolerated dose (MTD) from Phase 1-Randomized Arm
Maximum tolerated dose (MTD) from Phase 1: Subjects will receive a subretinal injection in the MTD concentration.
Genetic: OCU410
Subretinal administration of OCU410
Experimental: Phase 2 Dose Expansion: Lower Dose from Phase 1-Randomized Arm
Subjects will receive a subretinal injection of OCU410 in a Lower Dose concentration.
Genetic: OCU410
Subretinal administration of OCU410
No Intervention: Control Arm
No Intervention Control Arm: Subject will not receive any active study intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events))
Time Frame: 12 months (Screening to 12 months post OCU410 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).
12 months (Screening to 12 months post OCU410 administration)
Change in anatomy of ocular structures using Slit Lamp Biomicroscopy
Time Frame: 12 months (Screening to 12 months post OCU410 administration)
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 OCU410 administration)
Change in anatomy of ocular structures using Indirect ophthalmoscopy
Time Frame: 12 months (Screening to 12 months post OCU410 administration)
We will use Indirect ophthalmoscopy to visualize the anatomy of ocular structures before and after sub-retinal injections and follow-up visits.
12 months (Screening to 12 months post OCU410 administration)
Change from baseline in BCVA (Best Corrected Visual Acuity)
Time Frame: 12 months (Screening to 12 months post OCU410 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.
12 months (Screening to 12 months post OCU410 administration)
Change in Low Luminance Visual Acuity
Time Frame: 12 months (Screening to 12 months post OCU410 administration)
Measured by letter score. A higher score represents better vision
12 months (Screening to 12 months post OCU410 administration)
Change in the Intraocular Pressure (mmHg)
Time Frame: 12 months (Screening to 12 months post OCU410 administration)
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 OCU410 administration)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Humoral and cellular immune response
Time Frame: 12 months (Screening to 12 months post OCU410 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 OCU410 administration
12 months (Screening to 12 months post OCU410 administration)
Shedding of viral vector
Time Frame: 12 months (Screening to 12 months post OCU410 administration)
Blood samples will be collected for the assessment to determine AAV vector shedding in systemic circulation after OCU410 administration
12 months (Screening to 12 months post 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 to determine a change from baseline after OCU410 administration.
12 months (Screening to 12 months post OCU410 administration)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Structural Outcome: Change Using Qualitative and quantitative assessments of autofluorescence pattern (FAF)
Time Frame: 12 months (Screening to 12 months post OCU410 administration)
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 OCU410 administration)
Changes in National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ25)
Time Frame: 12 months (Screening to 12 months post OCU410 administration)
The National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ25) questionnaires will be completed to assess the impact of vision on quality of subject's life.
12 months (Screening to 12 months post OCU410 administration)
Change From Baseline in Mean Threshold Sensitivity (MAIA)
Time Frame: 12 months (Screening to 12 months post OCU410 administration)
Mean threshold sensitivity of all points will be determined to assess the macular functional response and determine GA progression.
12 months (Screening to 12 months post OCU410 administration)
Change from Baseline in drusen volume using SD-OCT
Time Frame: 12 months (Screening to 12 months post OCU410 administration)
Measurement of change in drusen volume will be determined using Spectral Domain OCT measurements.
12 months (Screening to 12 months post OCU410 administration)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ocugen

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 23, 2023

Primary Completion (Estimated)

September 23, 2025

Study Completion (Estimated)

September 23, 2025

Study Registration Dates

First Submitted

June 30, 2023

First Submitted That Met QC Criteria

August 25, 2023

First Posted (Actual)

August 30, 2023

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 7, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OCU410-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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