start date: September 27, 2018
estimated completion: May 2024
last updated: November 9, 2021
phase of development:
Phase 1/Phase 2
size / enrollment: 18
study description: MPS II is a rare X-linked recessive genetic disease caused by mutations in the iduronate-2-sulfatase gene (IDS). 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) where it may be secreted by transduced cells which may cross-correct non-transduced cells by taking up the functional enzyme. This is a Phase I/II, first-in-human, multicenter, open-label, single arm dose escalation study of RGX-121. Three, one time doses of RGX-121 will be studied in approximately 18 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.-121.
primary outcomes:
- Safety: 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 4.03).
- 24 Weeks
secondary outcomes:
- Safety: Number of participants with treatment-related adverse events
104 Weeks
- Biomarkers
Baseline, Week 2, Week 4, Week 8, Week 24, Week 48, Week 56, Week 104
- Biomarkers
Baseline, Week 1, Week 2, Week 4, Week 8, Week 24, Week 32, Week 48, Week 56, Week 104
- Change in neurodevelopmental parameters
Baseline, Week 48, Week 78, Week 104
- Change in neurodevelopmental parameters
Baseline, Week 48, Week 78, Week 104
- Change in neurodevelopmental parameters
Baseline, Week 48, Week 78, Week 104
inclusion criteria:
• Eligible Ages: 4 - 5
• Eligible Sexes: male
Inclusion Criteria:
Must meet any of the following criteria:
a. Has a documented diagnosis of MPS II AND has a neurocognitive testing score ≤ 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 administered between 3 to 36 months apart (Bayley or Kaufman) OR
c. 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
d. 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
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: Criteria:
Has contraindications for intracisternal injection, intracerebroventricular 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
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
