- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03580083
RGX-111 Gene Therapy in Patients With MPS I
December 4, 2023 updated by: REGENXBIO Inc.
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
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.
Study Overview
Status
Active, not recruiting
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
8
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Patient Advocacy
- Phone Number: 866-860-0117
- Email: MPSI@regenxbio.com
Study Locations
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RS
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Porto Alegre, RS, Brazil, 90035-903
- Hospital de Clinicas de Porto Alegre
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-
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-
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Tel HaShomer, Israel, 5265601
- Sheba Medical Center
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-
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California
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Orange, California, United States, 92868
- Children's Hospital of Orange County
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
4 months and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Has documented evidence of CNS involvement due to MPS I or documented diagnosis of severe MPS I
- 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:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dose 1; 1x10^10 GC/g brain mass of RGX-111
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Recombinant adeno-associated virus serotype 9 capsid containing α-L-iduronidase expression cassette
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Experimental: Dose 2; 5x10^10 GC/g brain mass of RGX-111
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Recombinant adeno-associated virus serotype 9 capsid containing α-L-iduronidase expression cassette
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety: Number of participants with treatment-related adverse events and serious adverse events
Time Frame: 24 Weeks
|
Number of participants with treatment-related adverse events and serious adverse events
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24 Weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety: Number of participants with treatment-related adverse events
Time Frame: 104 Weeks
|
Number of participants with treatment-related adverse events as assessed by CTCAE (Version 4.03)
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104 Weeks
|
Change in neurodevelopmental parameters
Time Frame: Baseline, Week 24, Week 52, Week 78, Week 104
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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).
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Baseline, Week 24, Week 52, Week 78, Week 104
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Change in neurodevelopmental parameters
Time Frame: Baseline, Week 24, Week 52, Week 78, Week 104
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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) .
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Baseline, Week 24, Week 52, Week 78, Week 104
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Change in neurodevelopmental parameters
Time Frame: Baseline, Week 24, Week 52, Week 78, Week 104
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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)) .
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Baseline, Week 24, Week 52, Week 78, Week 104
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Change in neurodevelopmental parameters
Time Frame: Baseline, Week 24, Week 52, Week 78, Week 104
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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).
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Baseline, Week 24, Week 52, Week 78, Week 104
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Change in adaptive behavior
Time Frame: Baseline, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104
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Change in baseline in adaptive behavior as measured by the Vineland Adaptive Behavior Scales, Third Edition (VABS-III)
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Baseline, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104
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Vector shedding
Time Frame: Baseline, Week 1, Week 4, Week 8, Week 16, Week 24
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As measured by vector concentration (quantitative polymerase chain reaction [qPCR] to RGX-111 deoxyribonucleic acid [DNA]) in CSF, serum, and urine
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Baseline, Week 1, Week 4, Week 8, Week 16, Week 24
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 3, 2019
Primary Completion (Actual)
March 1, 2023
Study Completion (Estimated)
October 1, 2024
Study Registration Dates
First Submitted
June 18, 2018
First Submitted That Met QC Criteria
July 5, 2018
First Posted (Actual)
July 9, 2018
Study Record Updates
Last Update Posted (Estimated)
December 6, 2023
Last Update Submitted That Met QC Criteria
December 4, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- RGX-111-002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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