Study to Assess the Safety and Efficacy of OCU410 for Geographic Atrophy
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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 Design
Arms and Interventions
| 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 |
Outcome Measures
Primary Outcome Measures
- Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events)) [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).
- Change in anatomy of ocular structures using Slit Lamp Biomicroscopy [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.
- Change in anatomy of ocular structures using Indirect ophthalmoscopy [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.
- Change from baseline in BCVA (Best Corrected Visual Acuity) [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.
- Change in Low Luminance Visual Acuity [12 months (Screening to 12 months post OCU410 administration)]
Measured by letter score. A higher score represents better vision
- Change in the Intraocular Pressure (mmHg) [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).
Secondary Outcome Measures
- Humoral and cellular immune response [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
- Shedding of viral vector [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
- Laboratory parameters including serum chemistry and hematology [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.
Other Outcome Measures
- Structural Outcome: Change Using Qualitative and quantitative assessments of autofluorescence pattern (FAF) [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.
- Changes in National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ25) [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.
- Change From Baseline in Mean Threshold Sensitivity (MAIA) [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.
- Change from Baseline in drusen volume using SD-OCT [12 months (Screening to 12 months post OCU410 administration)]
Measurement of change in drusen volume will be determined using Spectral Domain OCT measurements.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subjects 50 years of age or older.
-
BCVA of approximately 24 letters or more using Early Treatment Diabetic Retinopathy Study (ETDRS) chart (20/320 Snellen equivalent).
-
Fundus autofluorescence (FAF) imaging shows:
-
Total GA area ≥2.5 and ≤17.5 mm2 (1 and 7 disk areas [DA], respectively)
-
If GA is multifocal, at least one focal lesion must be ≥1.25 mm2 (0.5 DA), with the overall aggregate area of GA
-
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
-
Absence of any pattern of hyper-autofluorescence in the junctional zone of GA
Exclusion Criteria:
-
Previous treatment with a gene-therapy or cell therapy product
-
Previous treatment with any investigational drug or device within one year. The history of any investigational product with a washout period of up to six months will be evaluated on a case-by-case basis.
-
Previous treatment with Syfovre (Pegcetacoplan injection)
-
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Retina Consultants of Texas | Bellaire | Texas | United States | 77401 |
| 2 | Retina Foundation of the Southwest | Dallas | Texas | United States | 75231 |
Sponsors and Collaborators
- Ocugen
Investigators
- Study Director: Huma Qamar, MD, MPH, CMI, Ocugen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OCU410-101