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

Geographic Atrophy Clinical Trial

— ArMaDa  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06018558
• Other study ID #: OCU410-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 23, 2023
• Est. completion date: September 23, 2025

Study information

• Verified date: March 2024
• Source: Ocugen
• Contact: Umair Qazi, MD, MPH
• Phone: 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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 63
• Est. completion date: September 23, 2025
• Est. primary completion date: September 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrophy
• Geographic Atrophy

Intervention

Genetic:
• OCU410
Subretinal administration of OCU410

Locations

Country	Name	City	State
United States	B) Retina Consultants of Texas	Bellaire	Texas
United States	A) Retina Foundation of the Southwest	Dallas	Texas
United States	Duke Eye Center	Durham	North Carolina
United States	Mississippi Retina Associates	Jackson	Mississippi
United States	Gundersen Health System	La Crosse	Wisconsin
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	Structural Outcome: 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 OCU410 administration)
Other	Changes in National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ25)	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)
Other	Change From Baseline in Mean Threshold Sensitivity (MAIA)	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)
Other	Change from Baseline in drusen volume using SD-OCT	Measurement of change in drusen volume will be determined using Spectral Domain OCT measurements.	12 months (Screening to 12 months post OCU410 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 OCU410 administration)
Primary	Change in anatomy of ocular structures using Slit Lamp Biomicroscopy	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)
Primary	Change in anatomy of ocular structures using Indirect ophthalmoscopy	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)
Primary	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 OCU410 administration)
Primary	Change in Low Luminance Visual Acuity	Measured by letter score. A higher score represents better vision	12 months (Screening to 12 months post OCU410 administration)
Primary	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 OCU410 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 OCU410 administration	12 months (Screening to 12 months post OCU410 administration)
Secondary	Shedding of viral vector	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)
Secondary	Laboratory parameters including serum chemistry and hematology	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)