Mucopolysaccharidosis II
Conditions
Keywords
Hunter Syndrome, MPS II, nMPS II, nnMPS II
Brief summary
This is a multiregional open-label extension (OLE) to assess the safety, tolerability, and efficacy of long-term treatment with tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant intravenous (IV) enzyme replacement therapy (ERT) for Hunter syndrome (MPS II). Participants who complete at least through the Week 49 visit in Study DNLI-E-0002 and do not discontinue study intervention early and participants who complete Study DNLI-E-0007 will be enrolled in this OLE. All participants will receive DNL310 for up to 5 years from the time of entry in this OLE. Participants, site staff, and the Sponsor will remain blinded to the original treatment assignment for participants entering this OLE from Study DNLI-E-0007.
Interventions
Intravenous repeating dose
Sponsors
Denali Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * For participants from Study DNLI-E-0002 only: Completed at least through the Week 49 visit in Study DNLI-E-0002 and did not discontinue study intervention early * For participants from Study DNLI-E-0007 only: Completed the treatment period of 96 weeks in Cohort A for nMPS II participants and 48 weeks in Cohort B for nnMPS II participants Key
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and intensity of treatment-emergent adverse events (TEAEs) | 5 years | — |
| Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period | 5 years | — |
| Incidence and intensity of infusion-related reactions (IRRs) | 5 years | The intensity of IRRs will be assessed following each infusion of DNL310 using the categories of Mild, Moderate and Severe. IRRs will be summarized overall as well as stratified by intensity. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration | 5 years |
| Change from baseline in the Vineland-3 Adaptive Behavior Scale | 5 years |
| Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score | 5 years |
| Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT) | 5 years |
| Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations | 5 years |
| Liver volume within the normal range (normal vs abnormal) as measured by MRI | 5 years |
| Spleen volume within the normal range (normal vs abnormal) as measured by MRI | 5 years |
| Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II | 5 years |
Countries
Argentina, Belgium, Canada, Czechia, France, Germany, Italy, Netherlands, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Monitor
Denali Therapeutics
Outcome results
None listed