Safety and Tolerability of Subretinal OPGx-RDH12-1001 for LCA-Associated Inherited Retinal Degeneration (LCA-IRD)

This is a Phase 1b/2a multicenter, open-label, and non-randomized dose-escalation safety study of up to two vector doses of OPGx-RDH12 (300 µL) administered via unilateral injection in participants with Leber Congenital Amaurosis (LCA) with autosomal-recessive retinol dehydrogenase 12 (RDH12) gene mutation(s). Administration will occur via a cannula into the subretinal space, using the standard technique for delivery of other adeno-associated virus (AAV) therapies including Luxturna®, the first United States Food and Drug Administration (FDA)-approved ocular gene therapy. Up to 2 OPGx-RDH12 dose cohorts will be studied: 1E11 vg/eye (Cohort 1) and 3E11 vg/eye (Cohort 2). The treatment eye will be the eye with the worst visual function (as determined by visual acuity, full-field sensitivity testing \[FST\] and kinetic perimetry) or the non-dominant eye in cases of bilateral symmetric disease. Toxicity related to the administration of OPGx-RDH12 will be monitored in the eye using a comprehensive clinical monitoring plan and an Independent Data Monitoring Committee (IDMC). Each cohort will enroll 5 participants. The first 2 participants will be adults (≥18 years old), treated at least 1 month apart. One month after the second participant's treatment, safety and efficacy data from the adult participants will be submitted to FDA for review and approval to open the study to adolescent participants (12-17 years old). The IDMC will next determine whether adolescent participants may be enrolled in the same dose cohort. Three months after the third adolescent participant's treatment, the IDMC will review all safety and efficacy data from the cohort and determine whether to recommend escalation to the next dose cohort. Efficacy signals in Cohort 1 may justify conversion to a larger cohort of adolescent participants at the 1E11 vg/eye dose, with no further dose escalation.