Back to resultsRGX-111 Gene Therapy in Patients With MPS I
Primary Purpose
Mucopolysaccharidosis Type I (MPS I), Hurler Syndrome, Hurler-Scheie Syndrome
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
RGX-111
Sponsored by
About this trial
This is an interventional treatment trial for Mucopolysaccharidosis Type I (MPS I) focused on measuring MPS I , gene therapy, Hurler, Hurler- Scheie
Eligibility Criteria
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.
Sites / Locations
- Children's Hospital of Orange County
- Children's Hospital of Philadelphia
- Hospital de Clinicas de Porto Alegre
- Sheba Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dose 1; 1x10^10 GC/g brain mass of RGX-111
Dose 2; 5x10^10 GC/g brain mass of RGX-111
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Safety: Number of participants with treatment-related adverse events
Number of participants with treatment-related adverse events as assessed by CTCAE (Version 4.03)
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).
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) .
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)) .
Change in neurodevelopmental parameters
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).
Change in adaptive behavior
Change in baseline in adaptive behavior as measured by the Vineland Adaptive Behavior Scales, Third Edition (VABS-III)
Vector shedding
As measured by vector concentration (quantitative polymerase chain reaction [qPCR] to RGX-111 deoxyribonucleic acid [DNA]) in CSF, serum, and urine
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03580083
Brief Title
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
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 3, 2019 (Actual)
Primary Completion Date
April 2023 (Anticipated)
Study Completion Date
October 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
REGENXBIO Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucopolysaccharidosis Type I (MPS I), Hurler Syndrome, Hurler-Scheie Syndrome
Keywords
MPS I , gene therapy, Hurler, Hurler- Scheie
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Sequential Assignment Dose escalation
Masking
None (Open Label)
Masking Description
Open-Label
Allocation
Non-Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose 1; 1x10^10 GC/g brain mass of RGX-111
Arm Type
Experimental
Arm Title
Dose 2; 5x10^10 GC/g brain mass of RGX-111
Arm Type
Experimental
Intervention Type
Genetic
Intervention Name(s)
RGX-111
Intervention Description
Recombinant adeno-associated virus serotype 9 capsid containing α-L-iduronidase expression cassette
Primary Outcome Measure Information:
Title
Safety: Number of participants with treatment-related adverse events and serious adverse events
Description
Number of participants with treatment-related adverse events and serious adverse events
Time Frame
24 Weeks
Secondary Outcome Measure Information:
Title
Safety: Number of participants with treatment-related adverse events
Description
Number of participants with treatment-related adverse events as assessed by CTCAE (Version 4.03)
Time Frame
104 Weeks
Title
Change in neurodevelopmental parameters
Description
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
Title
Change in neurodevelopmental parameters
Description
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
Title
Change in neurodevelopmental parameters
Description
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
Title
Change in neurodevelopmental parameters
Description
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).
Time Frame
Baseline, Week 24, Week 52, Week 78, Week 104
Title
Change in adaptive behavior
Description
Change in baseline in adaptive behavior as measured by the Vineland Adaptive Behavior Scales, Third Edition (VABS-III)
Time Frame
Baseline, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104
Title
Vector shedding
Description
As measured by vector concentration (quantitative polymerase chain reaction [qPCR] to RGX-111 deoxyribonucleic acid [DNA]) in CSF, serum, and urine
Time Frame
Baseline, Week 1, Week 4, Week 8, Week 16, Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Hospital de Clinicas de Porto Alegre
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90035-903
Country
Brazil
Facility Name
Sheba Medical Center
City
Tel HaShomer
ZIP/Postal Code
5265601
Country
Israel
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
RGX-111 Gene Therapy in Patients With MPS I
We'll reach out to this number within 24 hrs