Leber Congenital Amaurosis, Retinitis Pigmentosa
Conditions
Keywords
NR2E3, Rhodopsin, Enhanced S-cone syndrome, Cep290
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 an additional 2 years. Participants from the Phase 1/2 study who previously received the investigational product (OCU400) in one eye may be eligible to receive OCU400 in the untreated fellow eye, provided they meet the inclusion/exclusion criteria and have completed week 48 follow up visit. 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. Enrollment for this study has closed.
Interventions
DRUGOCU400 Low Dose
subretinal injection of up to 1.66×10E10 vg/mL
DRUGOCU400 Med Dose
subretinal injection of up to 3.33×10E10 vg/mL
DRUGOCU400 High Dose
subretinal injection of up to 1.66×10E11 vg/mL
DRUGOCU400 Second Eye Dosing
subretinal injection of 1.0x10E11vg/mL in 250 μl
Sponsors
Ocugen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Diagnosis and main criteria for inclusion: Subjects meeting all inclusion criteria and none of the
Exclusion criteria
are eligible for study participation. Inclusion Criteria for Adult RP: 1. Males or females ≥ 18 years of age at the time of informed consent. 2. Confirmed genetic diagnosis of biallelic autosomal recessive NR2E3 mutations or autosomal dominant NR2E3 mutation for Subgroup 1 or autosomal dominant RHO mutations for Subgroup 2. 3. For the sentinel subject of Cohort 1-3, BCVA ≤ 20/160 in study eye or visual field less than 20° in any meridian, as measured by a III4e isopter or equivalent in study eye. 4. For non-sentinel subject, BCVA ≤ 20/50 or visual field less than 20° in any meridian, as measured by a III4e isopter or equivalent in study eye. 5. Able to perform a Multi-Luminance Mobility Testing (MLMT) using study eye, but unable to pass the MLMT at 1 lux, the lowest luminance level tested.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Contacts
STUDY_DIRECTORJennifer Henrick, RN, MS
Ocugen
STUDY_CHAIRMohamed Genead, MD
Ocugen
Outcome results
None listed