RGX-111 Gene Therapy in Patients With MPS I

REGENXBIO Inc.8 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Mucopolysaccharidosis Type I (MPS I)Hurler Syndrome Hurler-Scheie Syndrome

Interventions

RGX-111GENETIC

Recombinant adeno-associated virus serotype 9 capsid containing α-L-iduronidase expression cassette

Eligibility

Sex: ALLMin age: 4 Months

Medical Language ↔ Plain English

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.

Locations (4)

Children's Hospital of Orange County

Orange, California, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Sheba Medical Center

Tel Litwinsky, Israel

Outcomes

Primary Outcomes

Safety: Number of participants with treatment-related adverse events and serious adverse events

Number of participants with treatment-related adverse events and serious adverse events

Time frame: 24 Weeks

Secondary Outcomes

Safety: Number of participants with treatment-related adverse events

Number of participants with treatment-related adverse events as assessed by CTCAE (Version 4.03)

Time frame: 104 Weeks

Change in neurodevelopmental parameters

As measured by the Wechsler Abbreviated Scale of Intelligence, 2nd Edition (WASI-II).Based on their mean age equivalence score on the Vineland Adaptive Behavior Scales (#7) the subject will be assessed using the WASI-II ( for scores of \>/= 72 months).

Time frame: Baseline, Week 24, Week 52, Week 78, Week 104

Change in neurodevelopmental parameters

As measured by the Bayley Scale of Infant and Toddler Development, Third Edition (Bayley-III). Based on their mean age equivalence score on the Vineland Adaptive Behavior Scales (#7) the subject will be assessed using the BSID-III (for scores of \</ = 36 months or \>36 months to \<42 months) .

Time frame: Baseline, Week 24, Week 52, Week 78, Week 104

Change in neurodevelopmental parameters

As measured by the Wechsler Preschool and Primary Scales of Intelligence, Fourth Edition (WPPSI-IV). Based on their mean age equivalence score on the Vineland Adaptive Behavior Scales (#7) the subject will be assessed using the WPPSI-IV (for scores \>36 months to \< 42 months OR for scores of \>/= 42 months and \<72 months or \>36 months to \<42 months and unable to complete BSID-III (#4)) .

Time frame: Baseline, Week 24, Week 52, Week 78, Week 104

Data from ClinicalTrials.gov

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