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Trial record 1 of 1 for:    RGX-111
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RGX-111 Gene Therapy in Patients With MPS I

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03580083
Recruitment Status : Recruiting
First Posted : July 9, 2018
Last Update Posted : April 28, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis Type I (MPS I) Genetic: RGX-111 Phase 1 Phase 2

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. Two, one time doses of RGX-111 will be studied in approximately 5 subjects who have MPS I. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Sequential Assignment Dose escalation
Masking: None (Open Label)
Masking Description: Open-Label
Primary Purpose: Treatment
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
Actual Study Start Date : April 3, 2019
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : July 2023


Arm Intervention/treatment
Experimental: Dose 1; 1x10^10 GC/g brain mass of RGX-111 Genetic: RGX-111
Recombinant adeno-associated virus serotype 9 capsid containing α-L-iduronidase expression cassette

Experimental: Dose 2; 5x10^10 GC/g brain mass of RGX-111 Genetic: RGX-111
Recombinant adeno-associated virus serotype 9 capsid containing α-L-iduronidase expression cassette




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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)

  2. Change in neurodevelopmental parameters [ Time Frame: Baseline, Week 24, Week 36, Week 52, Week 78, Week 104 ]
    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).

  3. Change in neurodevelopmental parameters [ Time Frame: Baseline, Week 24, Week 36, Week 52, Week 78, Week 104 ]
    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) .

  4. Change in neurodevelopmental parameters [ Time Frame: Baseline, Week 24, Week 36, Week 52, Week 78, Week 104 ]
    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)) .

  5. Change in neurodevelopmental parameters [ Time Frame: 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).

  6. Change in neurodevelopmental parameters [ Time Frame: Baseline, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104 ]
    Change in baseline in neurodevelopment parameters of adaptive behavior as measured by the Vineland Adaptive Behavior Scales, Third Edition (VABS-III)

  7. Vector shedding [ Time Frame: 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



Information from the National Library of Medicine

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Ages Eligible for Study:   4 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 safely and successfully participate in the study.
  • Patient or Patient's legal guardian must be willing and able to provide written, signed informed consent.

Exclusion Criteria:

  • Has contraindications for intracisternal 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03580083


Contacts
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Contact: Patient Advocacy 866-860-0117 MPSI@regenxbio.com

Locations
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United States, California
Children's Hospital of Orange County Recruiting
Orange, California, United States, 92868
Contact: Nina Movsesyan    714-509-3008    nmovsesyan@choc.org   
Principal Investigator: Raymond Wang, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Katherine Armstrong    215-590-1427    armstronkl@email.chop.edu   
Principal Investigator: Can Ficicioglu, MD, PhD         
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Tracey Sikora    215-615-3238    tsikora@pennmedicine.upenn.edu   
Principal Investigator: Can Ficicioglu, MD, PhD         
Sponsors and Collaborators
Regenxbio Inc.

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Responsible Party: Regenxbio Inc.
ClinicalTrials.gov Identifier: NCT03580083    
Other Study ID Numbers: RGX-111-002
First Posted: July 9, 2018    Key Record Dates
Last Update Posted: April 28, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regenxbio Inc.:
MPS I , gene therapy, Hurler, Hurler- Scheie
Additional relevant MeSH terms:
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Mucopolysaccharidoses
Mucopolysaccharidosis I
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases