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)

NCT05371613 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: DNLI-E-00072024-510990-21-002021-005200-35
• Study Type: interventional
• Target: 63
• Locations: 15 countries
• Sites: 32

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.

Conditions

Mucopolysaccharidosis II

Keywords

Hunter Syndrome; MPS II; nMPS II; nnMPS II

Outcome Measures

Primary Outcomes (2)

• Percent change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A)

  24 weeks

• Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A)

  96 weeks

Secondary Outcomes (8)

• 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; Cohort A only)

  96 weeks

• Change from 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

• Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (Cohorts A and B)

  up to 48 weeks

Study Arms (3)

Cohort A: Participants with nMPS II

EXPERIMENTAL

Drug: tividenofusp alfa; Drug: idursulfase

Cohort B: Participants with nnMPS II

EXPERIMENTAL

Drug: tividenofusp alfa; Drug: idursulfase

Open-label Treatment Phase

EXPERIMENTAL

Participants who meet pre-specified criteria may receive DNL310 or idursulfase

Drug: tividenofusp alfa; Drug: idursulfase

Interventions

tividenofusp alfa DRUG

Intravenous repeating dose

Cohort A: Participants with nMPS II; Cohort B: Participants with nnMPS II; Open-label Treatment Phase

idursulfase DRUG

Intravenous repeating dose

Cohort A: Participants with nMPS II; Cohort B: Participants with nnMPS II; Open-label Treatment Phase

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Denali Therapeutics Inc.: lead

Study Sites (32)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

RECRUITING

Ann and Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

UNC Children's Research Institute

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

The University of Texas Medical School at Houston

Houston, Texas, 77030, United States

RECRUITING

University of Utah, PPDS

Salt Lake City, Utah, 84132, United States

RECRUITING

Sanatorio Mater Dei

Buenos Aires, Argentina

RECRUITING

Women's and Children's Hospital

North Adelaide, Australia

WITHDRAWN

UZ Antwerpen

Antwerp, Antwerpen, 2650, Belgium

RECRUITING

Universitair Ziekenhuis Brussel

Jette, Brussels Capital, 1090, Belgium

RECRUITING

Hospital de Clínicas de Porto Alegre (HCPA) - PPDS

Porto Alegre, Brazil

RECRUITING

Instituto Fernandes Figueira

Rio de Janeiro, Brazil

WITHDRAWN

University of Alberta - Faculty of Medicine & Dentistry

Edmonton, Alberta, Canada

RECRUITING

Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

RECRUITING

McGill University Health Center

Montreal, Quebec, H4A3J1, Canada

RECRUITING

Vseobecna Fakultni Nemocnice V Praze

Prague, 128 08, Czechia

RECRUITING

Hôpital Jeanne de Flandre

Lille, 59000, France

RECRUITING

SphinCS

Höchheim, Hochheim, 65239, Germany

RECRUITING

Medizinische Universität Lausitz - Carl Thiem

Cottbus, Germany

RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Misericordia

Udine, 33100, Italy

RECRUITING

Erasmus Medical Center - Sophia Children's Hospital

Rotterdam, Rotterdam, 3000, Netherlands

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

RECRUITING

Hospital Infantil Universitario Niño Jesus

Madrid, Madrid, 28009, Spain

RECRUITING

Drottning Silvias Barn Och Ungdomssjukhus

Gothenburg, 416 85, Sweden

RECRUITING

Cukurova University Medical Faculty Balcali Hospital

Adana, 1330, Turkey (Türkiye)

RECRUITING

Gazi Universitesi Tip Fakultesi

Çankaya, 06500, Turkey (Türkiye)

RECRUITING

Great Ormond Street Hospital for Children

London, London, WC1N 3JH, United Kingdom

RECRUITING

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, United Kingdom

RECRUITING

Royal Free Hospital

London, NW3 2QG, United Kingdom

RECRUITING

Salford Royal Hospital

Salford, M6 8HD, United Kingdom

RECRUITING

Related Links

• Denali Therapeutics

MeSH Terms

Conditions

Mucopolysaccharidosis II; Sudden Infant Death

Interventions

idursulfase

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infant Death

Study Officials

• Jose Alcantara Rodriguez, PharmD

  Denali Therapeutics Inc.

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials at Denali Therapeutics

CONTACT

clinical-trials@dnli.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2022
• First Posted: May 12, 2022
• Study Start: July 21, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); SE (1); TU (2); ES (2); CA (3); GB (4); CZ (1); BR (2); AU (1); AR (1); NL (1); US (8); DE (2); FR (1); IT (1)