Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis
- Conditions
- Retinitis PigmentosaLeber Congenital Amaurosis
- Interventions
- Registration Number
- NCT05203939
- Lead Sponsor
- Ocugen
- Brief Summary
This is a Phase 1/2 Study to Assess the Safety and Efficacy of OCU400 in patients with retinitis pigmentosa associated with NR2E3 and RHO mutations and in patients with LCA due to mutation(s) in CEP290 gene (OCU400-101). To document prospective eye pathology in the above subjects Investigators will also conduct a Natural History Study (OCU400-104)i
This is a multicenter study, which will be conducted in two phases and will enroll up to a total of 24 subjects in the OCU400-101 and 100 subjects in the OCU400-104 study.
- Detailed Description
This study will be conducted in two phases enrolling up to 24 subjects. Treated subjects will receive a single subretinal injection of OCU400 in the study eye.
This is a multicenter, open-label, dose-ranging study in two subgroups of subjects with three consecutive cohorts.
A total of 18 adult RP subjects from each of the following subgroups with Biallelic autosomal recessive NR2E3 mutations, autosomal dominant NR2E3 mutations or Autosomal dominant RHO mutations will be selected for dose escalation.
For the Phase I portion of the study, the 3+3 design for sequential dose-escalating cohorts will be used with scheduled 3 dosing levels between 9 and 18 subjects will be used to follow the design.
Up to 3 additional adult LCA patients with CEP290 mutations and at least 1 pediatric LCA subject, will be enrolled in the Phase 2 portion.
Sample Size Justification:
The trial will enroll up to 24 patients (18 adult RP, up to 3 LCA patients, and at least 1 pediatric LCA patient) in both Phase 1 and Phase 2 components.
Participants who meet eligibility criteria, will be enrolled, and receive a single subretinal injection of OCU400 in one study eye. Participants are considered to have completed this study if they complete the final EOS visit Week 48 (12 months following the IP dose). The study duration will be approximately 58 weeks for each participant and will be followed in Long Term Safety Follow Up for additional 2 years.
Natural History Study (OCU400-104, A Prospective and Retrospective Natural History Study of RP and LCA):
This is an observatory study for the prospective natural history of RP and LCA in adult and pediatric subjects. The study will also collect and review retrospective data and ophthalmology examination of natural history and progression of disease for all subjects starting with the earliest timepoint on or after the date of their diagnosis of RP or LCA.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 124
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 (Low Dose) OCU400 Low Dose Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation or RHO mutations subgroup Cohort 2 (Mid Dose) OCU400 Med Dose Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation or RHO mutations subgroup Cohort 3 (High Dose) OCU400 High Dose Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation, RHO mutations subgroup and LCA patients with CEP290 Pediatric Arm OCU400 Med Dose Pediatric subjects will receive the medium dose concentration and will have subjects with RP and LCA Phase 2 (High Dose) OCU400 High Dose Following DSMB confirmation, adult LCA subjects with CEP290 mutation will receive a medium dose concentration of OCU400. Adult Arm OCU400 Med Dose Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation, RHO mutations subgroup and LCA patients with CEP290
- Primary Outcome Measures
Name Time Method Study Drug-related adverse events (SDAE) 1 year Counts, frequencies and percentages of SDAEs. SDAE is a primary adverse event of interest and defined as AEs and SAEs that are direct subjects to the Study Drug only.
Treatment-Emergent adverse events (TEAEs) 1 year Counts, frequencies and percentages TEAEs. TEAEs are defined as an event that was not present prior to administration of the dose of study drug and present after the dose, or if it represents the exacerbation of an event that was present prior to the dose.
Serious adverse events (SAEs) 1 year Counts, frequencies and percentages of SAEs including Resulted in Death, Life-threatening, Hospitalization, Disabling/incapacitating, Congenital anomaly or birth defect and Medically significant AEs ( AE that did not meet any of the above criteria but could have jeopardized the subject and might have required medical or surgical intervention to prevent one of the outcomes listed above).
- Secondary Outcome Measures
Name Time Method Best-corrected visual acuity (BCVA) 1 year (Changes from baseline) Measured as the ETDRS letter score on the EVA tester or E-ETDRS charts. Electronic ETDRS Visual Acuity Testing Protocol will be followed (confidential).
Low-luminance visual acuity (LLVA) 1 year (Changes from baseline) Electronic Visual Acuity Tester (EVA) and a Sponsor specific Low-Luminance lens will be used. Early Treatment of Diabetic Retinopathy Study (ETDRS) will also be accepted as a backup.
Slit-lamp biomicroscopy 1 year (Changes from baseline) Changes in visual function.
Intraocular pressure (IOP) 1 year (Changes from baseline) IOP measurement by applanation or rebound tonometry. Confirmation with Goldmann tonometer if IOP reading is outside the normal range (8-21mmHg).
anti-AAV5 (anti Adeno-associated virus type 5) 1 year Blood samples will be collected for the assessment. These samples will be analyzed using validated assays at a bioanalytical laboratory.
Indirect ophthalmoscopy 1 year (Changes from baseline) If visual acuity is so poor that the participant is unable to count fingers or perceive hand motion, light perception will be tested with the indirect ophthalmoscope as the light source.
T-cell response 1 year Blood samples will be collected for the assessment. These samples will be analyzed using validated assays at a bioanalytical laboratory.
anti-hNR2E3 antibodies (hNR2E3 gene) 1 year Blood samples will be collected for the assessment. These samples will be analyzed using validated assays at a bioanalytical laboratory.
Trial Locations
- Locations (7)
Associated Retina Consultants
🇺🇸Phoenix, Arizona, United States
Ocugen Site 5 - University of California, San Diego (UCSD) - Shiley Eye Institute
🇺🇸La Jolla, California, United States
Ocugen Site 3 - Bascom Palmer Eye Institute
🇺🇸Miami, Florida, United States
Ocugen Site 6 - Emory University
🇺🇸Atlanta, Georgia, United States
Ocugen Site 2 - Casey Eye Institute - OHSU
🇺🇸Portland, Oregon, United States
Ocugen Site 8 - Mid Atlantic Retina - Wills Eye Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Ocugen Site 1 - Retina Foundation of the Southwest
🇺🇸Dallas, Texas, United States