Summary

Eligibility
for males ages 2-18 (full criteria)
Location
at UCSF
Dates
study started
estimated completion
Principal Investigator
by Paul Harmatz, MD (ucsf)

Description

Summary

This is a multicenter, multiregional, open-label study to assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL310, an investigational central nervous system (CNS)-penetrant enzyme replacement therapy (ERT), designed to treat both the peripheral and CNS manifestations of Mucopolysaccharidosis type II (MPS II; Hunter syndrome). The study has three cohorts:Cohort A will enroll participants with neuronopathic MPS II aged 5 to 10 years; Cohort B will enroll participants with MPS II, either neuronopathic or non-neuronopathic, aged 2 to 18 years; and Cohort C will enroll participants with neuronopathic MPS II aged ≥2 and <4 (Cohort C can include nMPS II participants ≥4 if the participant is a sibling of a participant aged ≥2 and <4). Participants, whose physicians feel they are deriving benefit, will have the opportunity to be reconsented into a safety extension for continued evaluation.

Official Title

A Phase 1/2, Multicenter, Open-Label Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL310 in Pediatric Participants With Hunter Syndrome

Keywords

Mucopolysaccharidosis II MPS II Hunter Syndrome nMPS II Mucopolysaccharidoses DNL310

Eligibility

You can join if…

Open to males ages 2-18

  • Confirmed diagnosis of MPS II
  • Cohort A: Participants aged 5 to 10 years with neuronopathic MPS II
  • Cohort B: Participants aged 2 to 18 years with non-neuronopathic MPS II, neuronopathic MPS II, or unknown phenotype
  • Cohort C: Participants aged ≥2 to <4 years with neuronopathic MPS II (this cohort can include participants ≥4 years of age if participant is a sibling of a participant ≥2 to <4 years of age)
  • For participants receiving intravenous iduronate 2-sulfatase (IDS) ERT, tolerated a minimum of 4 months of therapy during the period immediately prior to screening.

You CAN'T join if...

  • Unstable or poorly controlled medical condition(s) or significant medical or psychological comorbidity or comorbidities that, in the opinion of the investigator, would interfere with safe participation in the trial or interpretation of study assessments
  • Use of any CNS-targeted MPS II ERT within 3 months before study start for participants aged ≥5 years, and within 6 months before study start for participants aged <5 years.
  • Use of IDS gene therapy or stem cell therapy at any time
  • Clinically significant thrombocytopenia, other clinically significant coagulation abnormality, or significant active bleeding, or required treatment with an anticoagulant or more than two antiplatelet agents
  • Contraindication for lumbar punctures
  • Have a clinically significant history of stroke, status epilepticus, head trauma with loss of consciousness, or any CNS disease that is not MPS II-related within 1 year of screening
  • Have had a ventriculoperitoneal (VP) shunt placed, or any other brain surgery, or have a clinically significant VP shunt malfunction within 30 days of screening
  • Have any clinically significant CNS trauma or disorder that, in the opinion of the investigator, may interfere with assessment of study endpoints or make participation in the study unsafe

Locations

  • UCSF Benioff Children's Hospital accepting new patients
    Oakland California 94609 United States
  • Ann & Robert H. Lurie Children's Hospital of Chicago accepting new patients
    Chicago Illinois 60611 United States

Lead Scientist at University of California Health

  • Paul Harmatz, MD (ucsf)
    Professor, Pediatrics. Authored (or co-authored) 195 research publications.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Denali Therapeutics Inc.
ID
NCT04251026
Phase
Phase 1/2
Study Type
Interventional
Last Updated