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RGX-121 Gene Therapy in Children 5 Years of Age and Over With MPS II (Hunter Syndrome)

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: NCT04571970
Recruitment Status : Recruiting
First Posted : October 1, 2020
Last Update Posted : May 6, 2022
Sponsor:
Information provided by (Responsible Party):
Regenxbio Inc.

Brief Summary:
RGX-121 is a gene therapy which is designed to deliver a functional copy of the iduronate-2-sulfatase (IDS) gene to the central nervous system. This study is a phase I/II study to determine whether RGX-121 is safe, well tolerated, and potentially effective in children five years of age and over who have severe MPS II.

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis Type II (MPS II) Genetic: RGX-121 Phase 1 Phase 2

Detailed Description:
MPS II is a rare X-linked recessive genetic disease caused by mutations in the iduronate-2-sulfatase (IDS) gene. Enzyme replacement therapy (ERT) with recombinant idursulfase (ELAPRASE®) is the only approved product for the treatment of Hunter syndrome; however, ERT as currently administered does not cross the blood brain barrier and is therefore unable to address the unmet need in MPS II patients with CNS (neurocognition and behavior) involvement. RGX-121 is designed to deliver a healthy gene to cells in the CNS and iduronate-2-sulfatase (I2S) may then be secreted by transduced cells which may cross-correct non-transduced cells by taking up the functional enzyme. This is a Phase I/II, multicenter, open-label, single arm study of RGX-121. Approximately 6 children (≥ 5 years to < 18 years of age) who have severe (neuronopathic) MPS II could be enrolled into a single dose cohort and will receive a single dose of RGX-121 administered by IC or ICV injection. Safety will be the primary focus for the initial 24 weeks after treatment (primary study period). Following completion of the primary study period, participants will continue to be assessed (safety and efficacy) for up to a total of 104 weeks following treatment with RGX-121.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single-arm
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of RGX-121 in Children 5 Years of Age and Older With MPS II (Hunter Syndrome)
Actual Study Start Date : March 11, 2021
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : January 2024


Arm Intervention/treatment
Experimental: Single Arm
6.5 × 10^10 GC/g brain mass of RGX-121
Genetic: RGX-121
Recombinant adeno-associated virus serotype 9 capsid containing human iduronate-2-sulfatase expression cassette




Primary Outcome Measures :
  1. 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 as assessed by CTCAE (Version 5.0)


Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events and serious adverse events [ Time Frame: 104 Weeks ]
    Number of participants with treatment-related adverse events and serious adverse events as assessed by CTCAE (Version 5.0)

  2. Biomarkers [ Time Frame: Baseline, Week 1, Week 2, Week 4, Week 12, Week 24, Week 38, Week 52, Week 64, Week 78, Week 104 ]
    Change from baseline in Glycosaminoglycan levels (ng/mL)

  3. Biomarkers [ Time Frame: Baseline, Week 1, Week 2, Week 4, Week 12, Week 24, Week 38, Week 52, Week 64, Week 78, Week 104 ]
    Change from baseline in iduronate-2-sulfatase activity

  4. Change in neurodevelopmental parameters [ Time Frame: Baseline, Week 52, Week 104 ]
    Change from baseline in neurodevelopmental parameters of cognitive function as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III)

  5. Change in neurodevelopmental parameters [ Time Frame: Baseline, Week 52, Week 104 ]
    Change from baseline in neurodevelopmental parameters of cognitive function as measured by the Mullen Scales of Early Learning (MSEL)

  6. Change in neurodevelopmental parameters [ Time Frame: Baseline, Week 24, Week 52, Week 78, Week 104 ]
    Change from baseline in neurodevelopmental parameters as measured by the Vineland Adaptive Behavior Scales, 2nd Edition (VABS-II), Comprehensive Interview Form



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Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Meets any of the following criteria:

  1. Has a documented diagnosis of MPS II AND a neurocognitive testing score ≤ 1 ½ standard deviation (SD) from the test normative mean (BSID-III: 77 and MSEL Visual Reception: 35), OR
  2. Has a documented diagnosis of MPS II AND has a decline of ≥ 1 standard deviation on serial neurocognitive testing administered between 3 to 36 months apart (BSID-III Cognitive or MSEL Visual Reception), OR
  3. Has a relative clinically diagnosed with neuronopathic MPS II who has the same IDS mutation as the participant AND the participant in the opinion of a geneticist has inherited a neuronopathic form of MPS II, OR
  4. Has documented mutation(s) in IDS that in the opinion of a geneticist is known to result in a neuronopathic phenotype AND in the opinion of a clinician has a neuronopathic form of MPS II

Exclusion Criteria:

  1. Has contraindications for intracisternal injection, intracerebroventricular injection, or lumbar puncture
  2. Has contraindications for immunosuppressive therapy
  3. Has any neurocognitive deficit not attributable to MPS II or diagnosis of a neuropsychiatric condition
  4. Has had prior treatment with an AAV-based gene therapy product
  5. If receiving ELAPRASE® via intrathecal (IT) administration, must agree to discontinue IT idursulfase for the duration of the study
  6. Has experienced a serious hypersensitivity reaction to intravenous (IV) ELAPRASE®
  7. Is currently failing to respond to idursulfase (ELAPRASE®) IV due to neutralizing anti-idursulfase antibodies
  8. Has received any investigational product within 30 days of Day 1 or 5 half-lives before signing of the ICF, whichever is longer
  9. Has a platelet count <100,000 per microliter (µL), absolute neutrophil count <1.0 × 103/µL, or aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN at screening unless the participant has a previously known history of Gilbert's syndrome

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): NCT04571970


Contacts
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Contact: Patient Advocacy (866) 860-0117 MPSII@regenxbio.com

Locations
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United States, California
University of California San Francisco, Benioff Children's Hospital Recruiting
Oakland, California, United States, 94609
Contact: Matt Thura       matt.thura@ucsf.edu   
Principal Investigator: Dr. Paul Harmatz         
Canada, Quebec
McGill University Heath Center Recruiting
Montréal, Quebec, Canada, H4A 3J1
Contact: Dorothy McKelvey    514-934-1934 ext 23833    dorothy.mckelvey@muhc.mcgill.ca   
Principal Investigator: Dr. John Mitchell         
Sponsors and Collaborators
Regenxbio Inc.
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Responsible Party: Regenxbio Inc.
ClinicalTrials.gov Identifier: NCT04571970    
Other Study ID Numbers: RGX-121-1102
First Posted: October 1, 2020    Key Record Dates
Last Update Posted: May 6, 2022
Last Verified: May 2022
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 II
gene therapy
Hunter
Additional relevant MeSH terms:
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Mucopolysaccharidosis II
Mucopolysaccharidoses
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System