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RGX-121 Gene Therapy in Patients With MPS II (Hunter Syndrome)

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ClinicalTrials.gov Identifier: NCT03566043
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : July 12, 2018
Sponsor:
Information provided by (Responsible Party):
Regenxbio Inc.

Brief Summary:
RGX-121 is a gene therapy which is intended to deliver a functional copy of the iduronate-2-sulfatase (IDS) gene to the central nervous system. This study is a safety and dose ranging study to determine whether RGX-121 is safe and tolerated by patients with 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) is then expected to be secreted by transduced cells which are then expected to cross-correct non-transduced cells by taking up the functional enzyme. This is a Phase I/II, first-in-human, multicenter, open-label, dose escalation study of RGX-121. Two, one time doses of RGX-121 will be studied in approximately 6 pediatric subjects who have severe MPS II. 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-121.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 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 RGX-121 in Pediatric Subjects With MPS II (Hunter Syndrome)
Estimated Study Start Date : July 2018
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2021


Arm Intervention/treatment
Experimental: Dose 1
1.3x10^10 GC/g brain mass of RGX-121
Genetic: RGX-121
Recombinant adeno-associated virus serotype 9 capsid containing human iduronate-2-sulfatase expression cassette

Experimental: Dose 2
6.5x10^10 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. 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 as assessed by CTCAE (Version 4.03).


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. Biomarkers [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 24, Week 48, Week 56, Week 104 ]
    Change from baseline in Glycosaminoglycan levels (ng/mL)

  3. Biomarkers [ Time Frame: Baseline, Week 1, Week 2, Week 4, Week 8, Week 24, Week 32, Week 48, Week 56, Week 104 ]
    Change from baseline in iduronate-2-sulfatase activity

  4. Change in neurodevelopmental parameters [ Time Frame: Baseline, Week 48, Week 78, Week 104 ]
    Change from baseline in neurodevelopment parameters of cognitive, behavioral and adaptive function as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) or Kaufman Assessment Battery for Children, 2nd Edition (KABC-II). Based on their mean age equivalence score on the Vineland Adaptive Behavior Scales (outcome #7) , the child will be assessed using either the BSID-III (for scores of <36 months or </=42 months and unable to complete the KABC-II) OR the KABC-II (for scores of >/= 36 months).

  5. Change in neurodevelopmental parameters [ Time Frame: Baseline, Week 48, Week 78, Week 104 ]
    Change from baseline in neurodevelopment parameters of cognitive, behavioral and adaptive function as measured by the Mullen Scales of Early Learning (MSEL)

  6. Change in neurodevelopmental parameters [ Time Frame: Baseline, Week 48, Week 78, Week 104 ]
    Change from baseline in neurodevelopment parameters of cognitive, behavioral and adaptive function as measured by the Vineland Adaptive Behavior Scales, 2nd Edition, Comprehensive Interview Form



Information from the National Library of Medicine

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Ages Eligible for Study:   4 Months to 5 Years   (Child)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Genetic-based gender identity
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must meet any of the following criteria:
  • a. Has a documented diagnosis of MPS II and a has a neurocognitive testing score > 55 and ≤ 77 (Bayley or Kaufman), OR
  • b. Has a documented diagnosis of MPS II AND has a decline of ≥ 1 standard deviation on serial neurocognitive testing (Bayley or Kaufman) and a testing score > 55, OR
  • c. Has a relative diagnosed with severe MPS II who has the same IDS mutation as the subject AND in the opinion of a geneticist has inherited a severe form of MPS II
  • Patient's legal guardian must be willing and able to provide written, signed informed consent.
  • Is ≥4 months to <5 years of age.

Exclusion Criteria:

  • Has contraindications for intracisternal injection or lumbar puncture
  • Has contraindications for immunosuppressive therapy
  • Has neurocognitive deficit not attributable to MPS II or diagnosis of a neuropsychiatric condition
  • Has a (cerebral) ventricular shunt that may impact the proper dosing of the subject
  • Received hematopoietic stem cell transplantation
  • Received ELAPRASE® via intrathecal (IT) administration within 4 months of signing the ICF or experienced a serious hypersensitivity reaction to ELAPRASE®
  • Has a platelet count <100,000 per microliter (µL), absolute neutrophil count <1.3 × 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 subject 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): NCT03566043


Contacts
Contact: Jacob Wesley, Pharm D, MS 240-552-8181 patientadvocacy@regenxbio.com

Locations
United States, Pennsylvania
Children's Hospital of Pittsburgh - UPMC: Program for Neurodevelopment in Rare Disorders Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Jodi Martin - Research Coordinator    412-692-6351    sausjl@upmc.edu   
Contact: Dr. Maria Escolar - Principal Investigator       maria.escolar@chp.edu   
Sponsors and Collaborators
Regenxbio Inc.

Responsible Party: Regenxbio Inc.
ClinicalTrials.gov Identifier: NCT03566043     History of Changes
Other Study ID Numbers: RGX-121-101
First Posted: June 21, 2018    Key Record Dates
Last Update Posted: July 12, 2018
Last Verified: July 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 II
gene therapy
Hunter

Additional relevant MeSH terms:
Mucopolysaccharidoses
Mucopolysaccharidosis II
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