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Clinical Trial Details — Status: Enrolling by invitation

Administrative data

NCT number NCT06075537
Other study ID # DNLI-E-0008
Secondary ID 2023-503837-23
Status Enrolling by invitation
Phase Phase 2/Phase 3
First received
Last updated
Start date September 20, 2023
Est. completion date June 2027

Study information

Verified date May 2024
Source Denali Therapeutics Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Enrolling by invitation
Enrollment 99
Est. completion date June 2027
Est. primary completion date June 2027
Accepts healthy volunteers No
Gender All
Age group N/A to 18 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
tividenofusp alfa
Intravenous repeating dose

Locations

Country Name City State
Belgium Universitair Ziekenhuis Antwerpen Edegem Antwerpen
Canada Hospital for Sick Children Toronto Ontario
Czechia Vseobecna Fakultni Nemocnice V Praze Prague
Netherlands Erasmus Medical Center - Sophia Children's Hospital Rotterdam
United States UNC Children's Research Institute Chapel Hill North Carolina
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio

Sponsors (1)

Lead Sponsor Collaborator
Denali Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence and intensity of treatment-emergent adverse events (TEAEs) 5 years
Primary Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period 5 years
Primary Incidence and intensity of infusion-related reactions (IRRs) 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. 5 years
Secondary Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration 5 years
Secondary Change from baseline in the Vineland-3 Adaptive Behavior Scale 5 years
Secondary Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score 5 years
Secondary Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT) 5 years
Secondary Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations 5 years
Secondary Liver volume within the normal range (normal vs abnormal) as measured by MRI 5 years
Secondary Spleen volume within the normal range (normal vs abnormal) as measured by MRI 5 years
Secondary Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II 5 years
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