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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Mucopolysaccharidosis Type II (MPS II)
• Intervention / Treatment: Genetic: RGX-121

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.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Patient Advocacy; Phone Number: (866) 860-0117; Email: MPSII@regenxbio.com

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • McGill University Heath Center
• United States
  • California
    • Oakland, California, United States, 94609
      • University of California San Francisco, Benioff Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events and serious adverse events	Number of participants with treatment-related adverse events and serious adverse events as assessed by CTCAE (Version 5.0)	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events and serious adverse events	Number of participants with treatment-related adverse events and serious adverse events as assessed by CTCAE (Version 5.0)	104 Weeks
Biomarkers	Change from baseline in Glycosaminoglycan levels (ng/mL)	Baseline, Week 1, Week 2, Week 4, Week 12, Week 24, Week 38, Week 52, Week 64, Week 78, Week 104
Biomarkers	Change from baseline in iduronate-2-sulfatase activity	Baseline, Week 1, Week 2, Week 4, Week 12, Week 24, Week 38, Week 52, Week 64, Week 78, Week 104
Change in neurodevelopmental parameters	Change from baseline in neurodevelopmental parameters of cognitive function as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III)	Baseline, Week 52, Week 104
Change in neurodevelopmental parameters	Change from baseline in neurodevelopmental parameters of cognitive function as measured by the Mullen Scales of Early Learning (MSEL)	Baseline, Week 52, Week 104
Change in neurodevelopmental parameters	Change from baseline in neurodevelopmental parameters as measured by the Vineland Adaptive Behavior Scales, 2nd Edition (VABS-II), Comprehensive Interview Form	Baseline, Week 24, Week 52, Week 78, Week 104

Collaborators and Investigators

• Sponsor: REGENXBIO Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2021
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (Actual): October 1, 2020

Study Record Updates

• Last Update Posted (Actual): November 18, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: gene therapy; MPS II; Hunter
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidosis II; Mucopolysaccharidoses
• Other Study ID Numbers: RGX-121-1102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No