A Phase 1b/2a Open-Label, Dose-Exploration Study to Investigate the Safety and Tolerability of Subretinally Injected OPGx-RDH12 Administered in Participants With Leber Congenital Amaurosis With Autosomal-Recessive Retinol Dehydrogenase 12 Mutations
Opus Genetics, Inc
Summary
This study is an early-stage clinical trial (Phase 1b/2a) testing a gene therapy called OPGx-RDH12 for people with Leber Congenital Amaurosis (LCA) caused by mutations in the RDH12 gene, a rare genetic eye disease that leads to severe vision loss. The treatment is delivered as a one-time injection (300 µL) into the retina (subretinal space) of the worse-seeing eye, using a method similar to approved gene therapies like Luxturna. The study is designed to evaluate safety and effectiveness at two dose levels (1E11 and 3E11 viral genomes per eye) in small groups of 5 participants. Each group begins cautiously with 2 adults (age ≥18), treated at least one month apart, followed by FDA review before allowing adolescents (ages 12-17) to participate. An independent monitoring committee (IDMC) oversees safety throughout. After 3 adolescents are treated and followed for 3 months, the committee reviews all data to decide whether to move to a higher dose. However, if the lower dose (1E11 vg/eye) shows strong effectiveness in the first group, the study may expand by treating more adolescents at that same dose instead of increasing it further.
Description
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 d…