RGX-111 Gene Therapy in Patients With MPS I

study id #: NCT03580083

condition: Mucopolysaccharidosis Type I (MPS I), Hurler Syndrome, Hurler-Scheie Syndrome

status: Recruiting

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.

intervention: RGX-111

results: https://clinicaltrials.gov/ct2/show/results/NCT03580083

last updated: February 26, 2022

start date: April 3, 2019

estimated completion: March 2024

last updated: January 4, 2022

phase of development: Phase 1/Phase 2

size / enrollment: 11

study 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.

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
• 24 Weeks
  

secondary outcomes:

• Safety: Number of participants with treatment-related adverse events
  104 Weeks
• Change in neurodevelopmental parameters
  Baseline, Week 24, Week 52, Week 78, Week 104
• Change in neurodevelopmental parameters
  Baseline, Week 24, Week 52, Week 78, Week 104
• Change in neurodevelopmental parameters
  Baseline, Week 24, Week 52, Week 78, Week 104
• Change in neurodevelopmental parameters
  Baseline, Week 24, Week 52, Week 78, Week 104
• Change in adaptive behavior
  Baseline, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104
• Vector shedding
  Baseline, Week 1, Week 4, Week 8, Week 16, Week 24

inclusion criteria:

exclusion criteria: Criteria:

Has contraindications for intracisternal and intracerebroventricular injection or lumbar puncture.
Has contraindications for immunosuppressive therapy.
Has neurocognitive deficit not attributable to MPS I or diagnosis of a neuropsychiatric condition.
Received intrathecal (IT) laronidase at any time and experienced a significant AE considered related to IT administration
Has received intravenous (IV) laronidase at any time and experienced a significant AE considered related to IV administration.
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.
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.

sponsor: Regenxbio Inc.

contacts: Patient Advocacy, 866-860-0117, MPSI@regenxbio.com

trial center locations: United States,Brazil

• United States, California
  Children’s Hospital of Orange County
  Nina Movsesyan, 714-509-3008, nmovsesyan@choc.org
  
  
• United States, Pennsylvania
  Children’s Hospital of Philadelphia
  Amber Morris, 267-426-0186, MORRISA6@chop.edu
  
  
• United States, Pennsylvania
  University of Pennsylvania
  
  
• Brazil, RS
  Hospital de Clinicas de Porto Alegre
  Larissa Pozzebon Da Silva, (+55) 51 3359 6340, lapsilva@hcpa.edu.br