Clinical trial
A Phase 1/2/3 Multicenter, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamics of RGX-121 in Pediatric Subjects With MPS II (Hunter Syndrome)
Name
RGX-121-101
Description
RGX-121 is a gene therapy which is intended to deliver a functional copy of the iduronate-2-sulfatase gene (IDS) to the central nervous system. This study is a safety and efficacy, dose ranging study to determine whether RGX-121 is safe, effective and well-tolerated by patients with MPS II.
Trial arms
Trial start
2018-09-27
Estimated PCD
2024-05-01
Trial end
2025-05-01
Status
Active (not recruiting)
Phase
Early phase I
Treatment
RGX-121
Recombinant adeno-associated virus serotype 9 capsid containing human iduronate-2-sulfatase expression cassette
Arms:
Part 1: RGX-121 Dose 1, Part 1: RGX-121 Dose 2, Part 1: RGX-121 Dose 2 Expanded Cohort, Part 1: RGX-121 Dose 3, Part 1: RGX-121 Dose 3 Expanded Cohort, Part 2: RGX-121 Pivotal Expansion
Size
48
Primary endpoint
Part 1 Safety
24 Weeks
Part 2 Biomarkers
52 Weeks
Part 2 Biomarkers
104 weeks
Part 2 Neurodevelopmental parameters
52 Weeks
Part 2 Neurodevelopmental parameters
104 weeks
Eligibility criteria
Part 1 Inclusion Criteria:
* The subject's legal guardian(s) is (are) willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
* Is a male ≥4 months to \< 5 years of age on Day 1
* Must meet any of the following criteria:
* Has a documented diagnosis of MPS II and a has a neurocognitive testing score ≤ 77 (Bayley or Kaufman), OR
* 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 (Bayley or Kaufman) OR
* Has a relative clinically 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 OR
* Has documented mutation (s) in IDS that in the opinion of a geneticist is always known to result in a neuronopathic phenotype AND in the opinion of a clinician has a severe form of MPS II
Part 2 Inclusion Criteria:
* The subject's legal guardian(s) is (are) willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
* Is a male ≥4 months to \< 5 years of age on Day 1
* Has a documented diagnosis of neuronopathic MPS II. Neuronopathic MPS II can be documented with any of the following methods:
* Has a BSID-III Cognitive Composite score at or below -1 SD (85) from normative mean
* Has two consecutive neurodevelopmental assessments that support a decline on MSEL visual receptive, expressive language, or fine motor, or BSID-III cognition, expressive language, or fine motor ≥ 1 SD on serial neurocognitive testing administered between 3 to 36 months apart
* Has a relative clinically diagnosed with neuronopathic MPS II who has the same IDS mutation as the subject AND the subject, in the opinion of a geneticist, has inherited a neuronopathic form of MPS II
* Has documented mutation(s) in IDS known to result in a neuronopathic phenotype
Part 1 Exclusion Criteria:
* Has contraindications for intracisternal (IC) injection, intracerebroventricular (ICV) 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
* Has had prior treatment with an AAV-based gene therapy product
* Received ELAPRASE® via intrathecal (IT) administration within 4 months of signing the ICF or experienced a serious hypersensitivity reaction to ELAPRASE®
* Has received any investigational product within 30 days of Day 1 or 5 half-lives before signing the ICF, whichever is longer
Part 2 Exclusion Criteria:
* Has a contraindication for an IC injection, ICV 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
* Has had prior treatment with an AAV-based gene therapy product
* Is receiving idursulfase (ELAPRASE®) via intrathecal (IT) administration, or a blood brain barrier-crossing enzyme replacement therapy. Subjects receiving IT ELAPRASE® or a blood brain barrier-crossing ERT may enroll if they agree to discontinue these therapies starting at least 3 months prior to dosing with RGX-121, and for the 24 months of follow-up
* Has received any investigational product within 30 days of Day 1 or 5 half-lives before signing the ICF, whichever is longer
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2', 'PHASE3'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Dose escalation', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'Open Label'}}, 'enrollmentInfo': {'count': 48, 'type': 'ESTIMATED'}}
Updated at
2023-11-18
1 organization
1 product
1 indication
Product
RGX-121Indication
Mucopolysaccharidosis Type IIOrganization
REGENXBIO