Recruiting
Phase 2
Phase 3

Tividenofusp Alfa vs. Idursulfase

Sponsor:

Denali Therapeutics Inc.

Code:

NCT05371613

Conditions

Mucopolysaccharidosis II

Eligibility Criteria

Sex: All

Age: 2 - 25

Healthy Volunteers: Not accepted

Interventions

tividenofusp alfa

idursulfase

Study Details

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

Study ID

NCT05371613

Start date

Jul 21, 2022

Status verified date

Aug, 2025

Completion date

Dec, 2027

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 2 - 25

Healthy Volunteers: Not accepted

Key Inclusion Criteria:

  • 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 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 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

Enrollment

63 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort A: Participants with nMPS II

experimental: Cohort B: Participants with nnMPS II

experimental: Open-label Treatment Phase

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

Interventions

tividenofusp alfa

Intravenous repeating dose

idursulfase

Intravenous repeating dose

Primary outcome measure

  • Percent change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A) [ Time Frame: 24 weeks ]
  • Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A) [ Time Frame: 96 weeks ]

Central Contacts and Locations

Central contacts

Clinical Trials at Denali Therapeutics

clinical-trials@dnli.com

Locations

UCSF Benioff Children's Hospital Oakland

Recruiting

Oakland, California, United States, 94609

Contacts

Marissa Evans

Marissa.Evans@ucsf.edu

Principal Investigator:

Paul Harmatz, MD

Ann and Robert H Lurie Children's Hospital of Chicago

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Lindsey Lang

llang@luriechildrens.org

312-227-6712

Principal Investigator:

Barbara Burton, MD

Hackensack University Medical Center

Recruiting

Hackensack, New Jersey, United States, 07601

Contacts

Susan Mathus

susan.mathus@hmhn.org

Principal Investigator:

Helio Pedro, MD

UNC Children's Research Institute

Recruiting

Chapel Hill, North Carolina, United States, 27514

Contacts

Lindsay Torrice

Lindsay_torrice@med.unc.edu

Principal Investigator:

Joseph Muenzer, MD

Cincinnati Children's Hospital Medical Center

Recruiting

Cincinnati, Ohio, United States, 45229

Contacts

Laurie Bailey

laurie.bailey@cchmc.org

Principal Investigator:

Nancy Leslie, MD

Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Genevieve Nesom

nesomg@chop.edu

Principal Investigator:

Can Ficicioglu, MD

The University of Texas Medical School at Houston

Recruiting

Houston, Texas, United States, 77030

Contacts

Marilyn Garcia

marilyn.garcia@uth.tmc.edu

Principal Investigator:

Paul Hillman, MD

University of Utah, PPDS

Recruiting

Salt Lake City, Utah, United States, 84132

Contacts

Carrie Bailey

carrie.bailey@hsc.utah.edu

Principal Investigator:

David Viskochil, MD

University of Alberta - Faculty of Medicine & Dentistry

Recruiting

Edmonton, Alberta, Canada

Contacts

Kathy Schellevis

schellev@ualberta.ca

Principal Investigator:

Saadet Andrews, MD

Hospital for Sick Children

Recruiting

Toronto, Ontario, Canada, M5G1X8

Contacts

Ashley Wilson

ashley.wilson@sickkids.ca

Principal Investigator:

Michal Inbar-Feigenberg, MD

McGill University Health Center

Recruiting

Montreal, Quebec, Canada, H4A3J1

Contacts

Christine Gannon

christine.gannon@muhc.mcgill.ca

Patricia Deeb

patricia.deeb@muhc.mcgill.ca

Principal Investigator:

John Mitchell, MD

More Information

Sponsor

Denali Therapeutics Inc.

Last update posted

Aug 5, 2025

Last verified

Aug, 2025

Keywords

  • Hunter Syndrome
  • MPS II
  • nMPS II
  • nnMPS II

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Denali Therapeutics Inc. on 2025-08-05.