MPS II (Hunter Syndrome) is a rare X-linked recessive genetic disease caused by mutations in the iduronate-2-sulfatase gene (IDS). Enzyme replacement therapy (ERT) with recombinant idursulfase (ELAPRASE®) is the only approved product for the treatment of Hunter syndrome, however, ERT as currently administered does not cross the blood brain barrier and is therefore unable to address the unmet need in MPS II patients with central nervous system (CNS) (neurocognition and behavior) involvement. RGX-121 is designed to deliver a functional gene to cells in the CNS. Iduronate-2-sulfatase (I2S) may then be secreted by transduced cells, which may then cross-correct non-transduced cells by taking up the functional enzyme.~This is a Phase I/II/III study enrolling in two sequential parts. Part 1 is a Phase I/II, first-in-human, multicenter, open-label, single arm dose escalation study of RGX-121. Three one-time doses of RGX-121 will be studied in up to 16 pediatric subjects who have neuronopathic MPS II. Safety will be the primary focus for the initial 24 weeks after treatment (primary study period) whereupon, subjects will continue to be assessed (safety and efficacy) for up to a total of 104 weeks following treatment with RGX-121. Part 2 is a pivotal expansion, multicenter, open-label, single arm study of RGX-121. A single dose of RGX-121 will be studied in up to 30 pediatric patients who have been diagnosed with neuronopathic MPS II. Subjects will be assessed at various timepoints for 24 months after receiving RGX-121. Subjects will be given the opportunity to enroll in a separate 3-year long-term follow-up study in accordance with the US federal government guidelines for the safety follow-up of patients receiving gene therapy.
RGX-121 is a gene therapy which is intended to deliver a functional copy of the iduronate-2-sulfatase gene (IDS) to the central nervous system. This study is a safety and efficacy, dose ranging study to determine whether RGX-121 is safe, effective and well-tolerated by patients with MPS II.