Clinical trial NCT03580083: RGX-111 Gene Therapy in Patients With MPS I
Official title: A Phase I/II Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Intracisternal RGX-111 in Subjects With Mucopolysaccharidosis Type I
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Mucopolysaccharidosis Type I (MPS I)
Hurler Syndrome
Hurler-Scheie Syndrome
Keywords: MPS I , gene therapy, Hurler, Hurler- Scheie
Lead sponsor: REGENXBIO Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-09
Enrollment: 8
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Sequential Assignment Dose escalation
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety: Number of participants with treatment-related adverse events and serious adverse events
timeFrame: 24 Weeks
Secondary outcomes:
measure: Safety: Number of participants with treatment-related adverse events
timeFrame: 104 Weeks
measure: Change in neurodevelopmental parameters
timeFrame: Baseline, Week 24, Week 52, Week 78, Week 104
measure: Change in neurodevelopmental parameters
timeFrame: Baseline, Week 24, Week 52, Week 78, Week 104
measure: Change in neurodevelopmental parameters
timeFrame: Baseline, Week 24, Week 52, Week 78, Week 104
measure: Change in neurodevelopmental parameters
timeFrame: Baseline, Week 24, Week 52, Week 78, Week 104
measure: Change in adaptive behavior
timeFrame: Baseline, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104
measure: Vector shedding
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 16, Week 24
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: RS
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center
Study officials:
References: