RGX-111 Gene Therapy in Patients With MPS I

Regenxbio

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Hurler-Scheie Syndrome; Mucopolysaccharidosis Type I (MPS I); Hurler Syndrome

Treatments: Genetic: RGX-111

Study type: Interventional

Funder types: Industry

Identifiers

NCT03580083

RGX-111-002

Details and patient eligibility

About

RGX-111 is a gene therapy which is intended to deliver a functional copy of the α-L-iduronidase (IDUA) gene to the central nervous system. This is a safety and dose ranging study to determine whether RGX-111 is safe and tolerated by patients with MPS I.

Full description

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, dose escalation study of RGX-111. Up to 11 subjects with MPS I will be treated in 2 dose cohorts and will receive a single dose of RGX-111. 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-111.

Enrollment: 8 patients

Sex: All

Ages: 4+ months old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Has documented evidence of CNS involvement due to MPS I or documented diagnosis of severe MPS I
2. Subjects who have had HSCT may be enrolled in the study if the PI, medical monitor, and sponsor agree that he/she can participate in the study.

Exclusion criteria

1. Has contraindications for intracisternal and intracerebroventricular injection or lumbar puncture.
2. Has contraindications for immunosuppressive therapy.
3. Has neurocognitive deficit not attributable to MPS I or diagnosis of a neuropsychiatric condition.
4. Received intrathecal (IT) laronidase at any time and experienced a significant AE considered related to IT administration
5. Has received intravenous (IV) laronidase at any time and experienced a significant AE considered related to IV administration.
6. Received any investigational product within 30 days of Day 1 or 5 half-lives before signing of the Informed Consent Form (ICF), whichever is longer.
7. Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN at screening unless the subject has a previously known history of Gilbert's syndrome and a fractionated bilirubin that shows conjugated bilirubin <35% of total bilirubin.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 2 patient groups

Dose 1; 1x10^10 GC/g brain mass of RGX-111

Experimental group

Treatment:

Genetic: RGX-111

Dose 2; 5x10^10 GC/g brain mass of RGX-111

Experimental group

Treatment:

Genetic: RGX-111