COMPASS: A Study to Determine the Efficacy and Safety of DNL310 vs Idursulfase in Pediatric Participants With Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II)
Study Details
Study Description
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 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2/Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort A: Participants with nMPS II
|
Drug: DNL310
Intravenous repeating dose
Drug: Idursulfase
Intravenous repeating dose
|
| Experimental: Cohort B: Participants with nnMPS II
|
Drug: DNL310
Intravenous repeating dose
Drug: Idursulfase
Intravenous repeating dose
|
| Experimental: Open-label Treatment Phase Participants who meet pre-specified criteria may receive DNL310 or idursulfase |
Drug: DNL310
Intravenous repeating dose
Drug: Idursulfase
Intravenous repeating dose
|
Outcome Measures
Primary Outcome Measures
- Percent change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A only) [24 weeks]
- Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A only) [96 weeks]
Secondary Outcome Measures
- 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 distance walked in the Six-Minute Walk Test (6MWT; Cohort B only) [48 weeks]
- Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (Cohorts A and B) [up to 48 weeks]
- Liver volume within the normal range (normal vs abnormal) as measured by magnetic resonance imaging (MRI) (Cohorts A and B) [48 weeks]
- Spleen volume within the normal range (normal vs abnormal) as measured by MRI (Cohorts A and B) [48 weeks]
- Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B) [48 weeks]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Participants aged ≥2 to <6 years (Cohort A) or ≥6 to <17 years (Cohort B)
-
Confirmed diagnosis of MPS II (for Cohort A, nMPS II; for Cohort B, nnMPS II)
-
Be on maintenance enzyme replacement therapy (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 imagings (MRIs)
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCSF Benioff Children's Hospital Oakland | Oakland | California | United States | 94609 |
| 2 | UNC Children's Research Institute | Chapel Hill | North Carolina | United States | 27514 |
Sponsors and Collaborators
- Denali Therapeutics Inc.
Investigators
- Study Director: Jose Alcantara Rodriguez, PharmD, Denali Therapeutics Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DNLI-E-0007