A Phase 3, Open-Label Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of RGX 121 in Pediatric Participants With Neuronopathic MPS II (Hunter Syndrome)
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, efficacy, and pharmacodynamic dose ranging study to determine whether RGX-121 is safe, effective and well-tolerated by patients with MPS II (Hunter Syndrome)
• The participant'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 study-related procedures being performed.
• Is a male ≥ 4 months to \< 5 years of age on Day 1.
• Has a documented diagnosis of MPS II, with a confirmed neuronopathic phenotype.
• Has a BSID-III Cognitive Composite score at or below -1SD (85) from the normative mean.
• Has 2 consecutive neurodevelopment assessments that support a decline on MSEL Visual Reception, Expressive Language, or Fine Motor, or BSID-III Cognitive, Expressive Communication, or Fine Motor of ≥ 1 SD on serial neurodevelopment testing administered between 3 to 36 months apart. Evidence for neurodevelopmental decline can be provided from historical medical records.
• Has a relative clinically diagnosed with neuronopathic MPS II who has the same IDS variant(s) as the participant AND the participant, in the opinion of a geneticist, has inherited a neuronopathic form of MPS II. Evidence for support of a relative with neuronopathic MPS II should be provided through medical record documentation of neurodevelopmental function at or below -2 SD from the normative mean. If standard scores are unavailable to document SD from the normative mean, a developmental quotient (AEq/chronological age × 100) of ≤ 60 can be used to document neuronopathic MPS II.
• Has documented variant(s) in IDS known to result in a neuronopathic phenotype. The participant's neuronopathic phenotype will be confirmed by an independent genetic review, with documented supporting evidence from previously reported cases of the same variant(s).
• Has sufficient auditory and visual capacity, with or without aids, to complete the required protocol testing, and be compliant with wearing the aid, if applicable, on testing days.
• Able to ambulate 100 meters independently without use of assistive devices, if the participant is, based on the judgement of the investigator, of a chronological age at screening at which independent ambulation would typically be expected in a child with neuronopathic MPS II.
• Provision of signed and dated informed consent form (ICF) and willingness to comply with all study procedures and availability for the duration of the study.