Study of Gene Therapy NR082 to Treat Lebers Hereditary Optic Neuropathy LHON with ND4 Mutation Phase 123 Dose-Finding and Randomized Controlled Trial Evaluating Safety and Effectiveness in Patients Aged 12 to 75

What this Trial Is About

Researchers are investigating the safety and effectiveness of a gene therapy called NR082 for treating Lebers Hereditary Optic Neuropathy LHON caused by a mitochondrial ND4 gene mutation. The study includes two parts Part 1 is a Phase 12 dose-finding study involving adults aged 18 to 75 years to determine a safe and effective dose. Part 2 is a Phase 3 study with a safety run-in phase and a randomized, double-blind, sham-injection controlled trial involving participants aged 12 to 75 years. All participants have vision loss related to LHON with a specific genetic mutation and have had reduced visual acuity for more than 6 months but less than 10 years. In Part 1, participants receive a single intravitreal injection of NR082 at varying doses, starting with 1.5 109 viral genomes vg in 0.05 mL per eye. The Safety Review Committee SRC reviews safety data to decide on dose adjustments. Part 2 starts with a safety run-in phase where six subjects, including at least one minor aged 12 to under 18, receive a higher dose of 4.5 109 vg in 0.05 mL per eye. After at least 6 weeks of monitoring and SRC approval, the study continues with a randomized, double-blind phase comparing NR082 injections to sham injections in one eye. Participants will be monitored through various visits over time to assess safety and vision outcomes. Safety and tolerability are tracked at multiple timepoints up to 12 weeks in Part 1, and up to 52 weeks in Part 2. Researchers will evaluate visual acuity improvements, immune responses, and quality of life changes. Eye examinations, genetic testing, and comprehensive safety assessments will be conducted throughout the study. The total study duration includes initial dose-finding, safety monitoring, and long-term follow-up to understand the effects of NR082 treatment.

Gene Therapy Clinical Trial for the Treatment Of Leber's HereDitary Optic Neuropathy