This is a Phase 2/3, multiregional, two-arm, double-blind, randomized, active (standard-of-care)-controlled study of the efficacy and safety of tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant enzyme-replacement therapy (ERT) for mucopolysaccharidosis type II (MPS II).
Participants may also qualify to enter an open-label treatment phase with DNL310 or idursulfase based on pre-specified criteria.
Participants aged ≥2 to <6 years (Cohort A) or ≥6 to <26 years (Cohort B)
Confirmed diagnosis of MPS II (for Cohort A, nMPS II; for Cohort B, nnMPS II)
Have no history of treatment with enzyme replacement therapy (ERT) OR not have received continuous ERT for 4 months prior to screening OR be on maintenance ERT and have tolerated idursulfase for a minimum of 4 months prior to screening
Have a documented mutation of other genes or genetic diagnosis accounting for developmental delay
Previously received an iduronate 2-sulfatase (IDS) gene therapy or stem cell therapy
Received any CNS-targeted MPS ERT within 6 months prior to screening
Have a contraindication for lumbar punctures and/or magnetic resonance imaging (MRI)
Denali Therapeutics Inc.
Lead sponsor