A Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) Vs Idursulfase in Pediatric and Young Adult Participants with Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II)
- Conditions
- Mucopolysaccharidosis II
- Interventions
- Registration Number
- NCT05371613
- Lead Sponsor
- Denali Therapeutics Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 54
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open-label Treatment Phase tividenofusp alfa Participants who meet pre-specified criteria may receive DNL310 or idursulfase Cohort B: Participants with nnMPS II tividenofusp alfa - Cohort A: Participants with nMPS II tividenofusp alfa - Cohort A: Participants with nMPS II idursulfase - Cohort B: Participants with nnMPS II idursulfase - Open-label Treatment Phase idursulfase Participants who meet pre-specified criteria may receive DNL310 or idursulfase
- Primary Outcome Measures
Name Time Method Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A) 96 weeks Percent change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A) 24 weeks
- Secondary Outcome Measures
Name Time Method 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 serum neurofilament light chain (NfL) (Cohort A only) 96 weeks Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (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 Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B) 48 weeks Change from baseline in the Vineland-3 Adaptive Behavior Composite (ABC; 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
Trial Locations
- Locations (30)
Drottning Silvias Barn Och Ungdomssjukhus
🇸🇪Göteborg, Sweden
Cukurova University Medical Faculty Balcali Hospital
🇹🇷Adana, Turkey
Gazi Universitesi Tip Fakultesi
🇹🇷Çankaya, Turkey
Birmingham Women's and Children's NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Great Ormond Street Hospital for Children
🇬🇧London, United Kingdom
Hospital Infantil Universitario Niño Jesus
🇪🇸Madrid, Spain
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
Ann and Robert H Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
UNC Children's Research Institute
🇺🇸Chapel Hill, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
The University of Texas Medical School at Houston
🇺🇸Houston, Texas, United States
University of Utah, PPDS
🇺🇸Salt Lake City, Utah, United States
Sanatorio Mater Dei
🇦🇷Buenos Aires, Argentina
Women's and Children's Hospital
🇦🇺North Adelaide, Australia
Universitair Ziekenhuis Brussel
🇧🇪Jette, Brussels, Belgium
UZ Antwerpen
🇧🇪Antwerpen, Belgium
Hospital de Clínicas de Porto Alegre (HCPA) - PPDS
🇧🇷Porto Alegre, Brazil
Instituto Fernandes Figueira
🇧🇷Rio De Janeiro, Brazil
University of Alberta - Faculty of Medicine & Dentistry
🇨🇦Edmonton, Alberta, Canada
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
McGill University Health Center
🇨🇦Montreal, Quebec, Canada
Vseobecna Fakultni Nemocnice V Praze
🇨🇿Praha, Czechia
Hôpital Jeanne de Flandre
🇫🇷Lille, France
Universitätsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
SphinCS
🇩🇪Hochheim, Germany
Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Misericordia
🇮🇹Udine, Italy
Erasmus Medical Center - Sophia Children's Hospital
🇳🇱Rotterdam, Netherlands
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
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