RGX-111 Gene Therapy in Patients With MPS I

Phase 1

Active, not recruiting

• Conditions: Hurler-Scheie Syndrome; Mucopolysaccharidosis Type I (MPS I); Hurler Syndrome
• Interventions: Genetic: RGX-111

• Registration Number: NCT03580083
• Lead Sponsor: REGENXBIO Inc.

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2018-06-18
• Study First Submitted QC: 2018-07-05
• Study First Posted: 2018-07-09
• Study Start: 2019-04-03
• Primary Completion: 2023-03-01
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-04
• Last Update Posted: 2023-12-06
• Study Completion: 2024-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 8

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose 1; 1x10^10 GC/g brain mass of RGX-111	RGX-111	-
Dose 2; 5x10^10 GC/g brain mass of RGX-111	RGX-111	-

Primary Outcome Measures

Name	Time	Method
Safety: Number of participants with treatment-related adverse events and serious adverse events	24 Weeks	Number of participants with treatment-related adverse events and serious adverse events

Secondary Outcome Measures

Name	Time	Method
Change in neurodevelopmental parameters	Baseline, Week 24, Week 52, Week 78, Week 104	Change from baseline in neurodevelopment parameters of attention as measured by the Tests of Variables of Attention, Version 9 (TOVA) if able to complete the WASI-II (as defined in #3).
Safety: Number of participants with treatment-related adverse events	104 Weeks	Number of participants with treatment-related adverse events as assessed by CTCAE (Version 4.03)
Change in adaptive behavior	Baseline, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104	Change in baseline in adaptive behavior as measured by the Vineland Adaptive Behavior Scales, Third Edition (VABS-III)
Vector shedding	Baseline, Week 1, Week 4, Week 8, Week 16, Week 24	As measured by vector concentration (quantitative polymerase chain reaction \[qPCR\] to RGX-111 deoxyribonucleic acid \[DNA\]) in CSF, serum, and urine

Trial Locations

Locations (4)

Hospital de Clinicas de Porto Alegre; 🇧🇷 Porto Alegre, RS, Brazil

Sheba Medical Center; 🇮🇱 Tel HaShomer, Israel

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States