start date: March 11, 2021
estimated completion: September 2023
last updated: September 28, 2021
phase of development:
Phase 1/Phase 2
size / enrollment: 6
study 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.
primary outcomes:
- 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 outcomes:
- Number of participants with treatment-related adverse events and serious adverse events
104 Weeks
- Biomarkers
Baseline, Week 1, Week 2, Week 4, Week 12, Week 24, Week 38, Week 52, Week 64, Week 78, Week 104
- Biomarkers
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
Baseline, Week 52, Week 104
- Change in neurodevelopmental parameters
Baseline, Week 52, Week 104
- Change in neurodevelopmental parameters
Baseline, Week 24, Week 52, Week 78, Week 104
inclusion criteria:
• Eligible Ages: 5 - 17
• Eligible Sexes: male
Inclusion Criteria:
Meets any of the following criteria:
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
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
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
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: Criteria:
Has contraindications for intracisternal injection, intracerebroventricular injection, or lumbar puncture
Has contraindications for immunosuppressive therapy
Has any neurocognitive deficit not attributable to MPS II or diagnosis of a neuropsychiatric condition
Has had prior treatment with an AAV-based gene therapy product
If receiving ELAPRASE® via intrathecal (IT) administration, must agree to discontinue IT idursulfase for the duration of the study
Has experienced a serious hypersensitivity reaction to intravenous (IV) ELAPRASE®
Is currently failing to respond to idursulfase (ELAPRASE®) IV due to neutralizing anti-idursulfase antibodies
Has received any investigational product within 30 days of Day 1 or 5 half-lives before signing of the ICF, whichever is longer
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
