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RGX-111 Gene Therapy in Patients With MPS I

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ClinicalTrials.gov Identifier: NCT03580083
Recruitment Status : Recruiting
First Posted : July 9, 2018
Last Update Posted : August 28, 2018
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

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, 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.

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 Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of RGX-111 in Subjects With MPS I
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2021


Arm Intervention/treatment
Experimental: Dose 1; 2x10^9 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; 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




Primary Outcome Measures :
  1. Safety: Number of participants with treatment-related adverse events and serious adverse events [ Time Frame: 24 Weeks ]

Secondary Outcome Measures :
  1. Safety: Number of participants with treatment-related adverse events and serious adverse events [ Time Frame: 104 Weeks ]
  2. Biomarkers: Change from baseline in Glycosaminoglycan levels (ng/mL) in CSF, urine and plasma [ Time Frame: Baseline, Week 1, Week 2, Week 4, Week 8, Week 24, Week 32, Week 40, Week 48, Week 52, Week 56, Week 78, Week 104 ]
  3. Biomarkers Change from baseline in α-L-iduronidase activity in CSF, and plasma [ Time Frame: Baseline, Week 1, Week 2, Week 4, Week 8, Week 24, Week 32, Week 40, Week 48, Week 52, Week 56, Week 78, Week 104 ]
  4. Change from baseline in neurodevelopment [ Time Frame: Baseline, Week 24, Week 52 , Week 104 ]
    Change from baseline in neurodevelopment parameters of IQ as measured by the Wechsler Abbreviated Scale of Intelligence, 2nd Edition (WASI-II).

  5. Change from baseline in neurodevelopment [ Time Frame: Baseline, Week 24, Week 52 ]
    Change from baseline in neurodevelopment parameters of attention as measured by the Tests of Variables of Attention, Version 9 (TOVA).



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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must meet any of the following criteria:

    • Has documented evidence of early- stage neurocognitive deficit due to MPS I, defined as either of the following:

      1. A score of ≥ 1 standard deviation below mean on IQ testing or in 1 domain of neuropsychological function ( verbal comprehension, attention, or perceptual reasoning).
      2. A decline of >1 standard deviation on sequential testing
    • 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
Contact: Jacob Wesley, Pharm D, MS 240-552-8181 patientadvocacy@regenxbio.com

Locations
United States, Pennsylvania
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.

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

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:
Mucopolysaccharidoses
Mucopolysaccharidosis I
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases