RGX-111 Gene Therapy in Patients With MPS I

Mucopolysaccharidosis type I (MPS I) is a rare recessive genetic disease caused by a deficiency of α-L-iduronidase (IDUA) leading to an accumulation of glycosaminoglycans (GAGs) in tissues of patients with MPS I. While currently available therapies, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT), provide clinical benefit over untreated disease progression, they still possess significant limitations. ERT does not cross the blood-brain barrier and, therefore, does not treat the central nervous system (CNS) effects of the disease, and HSCT has clinically relevant morbidity and mortality and is not able to completely treat the CNS effects. RGX-111 is designed to deliver a functioning gene enabling the production of IDUA in the brain. This is a Phase I/II , first-in-human, multicenter, open-label, single-arm dose escalation study of RGX 111. Up to 21 subjects with MPS I will be treated in 2 dose cohorts and will receive a single dose of RGX-111 administered using an investigational device by IC or IVR injection. Safety will be the primary focus for the initial 24 weeks after treatment (primary study period). Following completion of the primary study period, subjects will continue to be assessed (safety and efficacy) for up to a total of 104 weeks following treatment with RGX-111. At the end of the study, all subjects will be invited to participate in a long-term observational follow-up study.