Mucopolysaccharidosis II
Conditions
Keywords
Hunter Syndrome, MPS II, nMPS II, nnMPS II
Brief summary
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.
Interventions
Intravenous repeating dose
DRUGidursulfase
Intravenous repeating dose
Sponsors
Denali Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion 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 Key
Exclusion criteria
* 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) * Participated in any other investigational drug study or used an investigational drug within 60 days prior to screening or intend to receive another investigational drug during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A) | 96 weeks |
| Ratio to baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A) | 24 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B) | 48 weeks |
| Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)(Cohort A only) | 96 weeks |
| Change from baseline in the Vineland-3 Adaptive Behavior Composite (ABC) score (Cohort A only) | 96 weeks |
| Ratio to baseline in serum neurofilament light chain (NfL) (Cohort A only) | 96 weeks |
| Change from baseline in distance walked in the Six-Minute Walk Test (6MWT; Cohort B only) | 48 weeks |
| Liver volume within the normal range (normal vs abnormal) as measured by magnetic resonance imaging (MRI) (Cohorts A and B) | 48 weeks |
| Ratio to baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (normalized to creatinine) (Cohorts A and B) | up to 48 weeks |
| Spleen volume within the normal range (normal vs abnormal) as measured by MRI (Cohorts A and B) | 48 weeks |
Countries
Argentina, Belgium, Brazil, Canada, Czechia, France, Germany, Italy, Netherlands, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORJose Alcantara Rodriguez, PharmD
Denali Therapeutics Inc.
Outcome results
None listed