for males ages 5-17 (full criteria)
at Oakland, California and other locations
study started
completion around
Principal Investigator
by Paul Harmatz
Headshot of Paul Harmatz
Paul Harmatz



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.

Official Title

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)


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.


Mucopolysaccharidosis Type II (MPS II), MPS II, gene therapy, Hunter, Mucopolysaccharidosis II, Mucopolysaccharidoses, RGX-121


You can join if…

Open to males ages 5-17

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

You CAN'T join if...

  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


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

Lead Scientist at UCSF

  • Paul Harmatz
    Dr. Paul Harmatz is a gastroenterologist who specializes in mucopolysaccharidoses (MPS) and other lysosomal storage diseases (genetic disorders in which a lack of certain enzymes results in progressive damage to cells and organ systems). He leads a team of specialists who diagnose and care for patients with these rare diseases, offering therapies such as weekly enzyme infusion.


in progress, not accepting new patients
Start Date
Completion Date
Phase 1/2 research study
Study Type
Expecting 6 study participants
Last Updated