Duchenne muscular dystrophy (Duchenne) is a rare genetic disorder, caused by mutations in the gene responsible for making dystrophin, a protein of central importance for muscle cell structure and function. The absence of functional dystrophin protein in individuals with Duchenne results in cell damage during muscle contraction leading to cell death, inflammation, and fibrosis in muscle tissues, and ultimately progressive muscle weakness. RGX-202 is designed to use the AAV8 vector to deliver a transgene to muscle cells that encodes a novel microdystrophin that includes the functional elements of naturally occurring dystrophin including the C-Terminal (CT) domain.

This is a multicenter, phase I/II/III, open-label study to evaluate the safety, tolerability, pharmacodynamics (microdystrophin protein levels), pharmacokinetic, and clinical efficacy of RGX-202 when administered IV as one-time dose to ambulant male participants with Duchenne. A comprehensive, short-term, prophylactic immunosuppression regimen will be administered during treatment to mitigate a potential immune response. This study is being conducted in three sequential parts: a phase I/II study (Part 1), a phase 3 pivotal study (Part 2) and a confirmatory study (Part 3). Part 1 will study a one-time dose of RGX-202 (1×10^14 or 2×10^14 GC/kg) in up to 15 participants with Duchenne. In part 1, the primary objective is to evaluate the safety and tolerability of RGX-202 through 52 weeks. Part 2 (Pivotal Expansion) will study a single dose of RGX-202 (2×10^14 GC/kg) in approximately 30 participants. After the last Part 2 participant is dosed, enrollment into the confirmatory study (Part 3) will be initiated. The target enrollment for the confirmatory study (Part 3) is approximately 30 participants. Participants will be assessed at various time points for 104 weeks after receiving RGX-202. All participants will be given the opportunity to enroll in a separate long-term follow-study in accordance with the US federal government guidelines for the safety follow-up of patients receiving gene therapy.