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) (COMPASS)

September 4, 2026 updated by: Denali Therapeutics Inc.

A Phase 2/3, Multicenter, Double-Blind, Randomized Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic or Non-Neuronopathic Mucopolysaccharidosis Type II

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Sanatorio Mater Dei
  • Belgium
    • Antwerpen
      • Antwerp, Antwerpen, Belgium, 2650
        • UZ Antwerpen
    • Brussels Capital
      • Jette, Brussels Capital, Belgium, 1090
        • Universitair Ziekenhuis Brussel
  • Brazil
      • Porto Alegre, Brazil
        • Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada
        • University of Alberta - Faculty of Medicine & Dentistry
    • Ontario
      • Toronto, Ontario, Canada, M5G1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H4A3J1
        • McGill University Health Center
  • Czechia
      • Prague, Czechia, 128 08
        • Vseobecna fakultni nemocnice v Praze
  • France
      • Lille, France, 59000
        • Hôpital Jeanne de Flandre
  • Germany
      • Cottbus, Germany
        • Medizinische Universität Lausitz - Carl Thiem
    • Hochheim
      • Höchheim, Hochheim, Germany, 65239
        • SphinCS
  • Italy
      • Udine, Italy, 33100
        • Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Misericordia
  • Netherlands
    • Rotterdam
      • Rotterdam, Rotterdam, Netherlands, 3000
        • Erasmus Medical Center - Sophia Children's Hospital
  • Spain
    • Barcelona
      • Barcelona, Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron
    • Madrid
      • Madrid, Madrid, Spain, 28009
        • Hospital Infantil Universitario Nino Jesus
  • Sweden
      • Gothenburg, Sweden, 416 85
        • Drottning Silvias Barn Och Ungdomssjukhus
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 1330
        • Cukurova University Medical Faculty Balcali Hospital
      • Çankaya, Turkey (Türkiye), 06500
        • Gazi Universitesi Tip Fakultesi
  • United Kingdom
      • Birmingham, United Kingdom
        • Birmingham Women's and Children's NHS Foundation Trust
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital
      • Salford, United Kingdom, M6 8HD
        • Salford Royal Hospital
    • London
      • London, London, United Kingdom, WC1N 3JH
        • Great Ormond Street Hospital for Children
  • United States
    • California
      • Oakland, California, United States, 94609
        • UCSF Benioff Children's Hospital Oakland
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann and Robert H Lurie Children's Hospital of Chicago
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • UNC Children's Research Institute
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas Medical School at Houston
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah, PPDS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 16 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort A: Participants with nMPS II
Drug: tividenofusp alfa
Intravenous repeating dose
Drug: idursulfase
Intravenous repeating dose
Experimental: Cohort B: Participants with nnMPS II
Drug: tividenofusp alfa
Intravenous repeating dose
Drug: idursulfase
Intravenous repeating dose
Experimental: Open-label Treatment Phase
Participants who meet pre-specified criteria may receive DNL310 or idursulfase
Drug: tividenofusp alfa
Intravenous repeating dose
Drug: idursulfase
Intravenous repeating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A)
Time Frame: 96 weeks
96 weeks
Ratio to baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A)
Time Frame: 24 weeks
24 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)(Cohort A only)
Time Frame: 96 weeks
96 weeks
Change from baseline in distance walked in the Six-Minute Walk Test (6MWT; Cohort B only)
Time Frame: 48 weeks
48 weeks
Liver volume within the normal range (normal vs abnormal) as measured by magnetic resonance imaging (MRI) (Cohorts A and B)
Time Frame: 48 weeks
48 weeks
Spleen volume within the normal range (normal vs abnormal) as measured by MRI (Cohorts A and B)
Time Frame: 48 weeks
48 weeks
Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B)
Time Frame: 48 weeks
48 weeks
Change from baseline in the Vineland-3 Adaptive Behavior Composite (ABC) score (Cohort A only)
Time Frame: 96 weeks
96 weeks
Ratio to baseline in serum neurofilament light chain (NfL) (Cohort A only)
Time Frame: 96 weeks
96 weeks
Ratio to baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (normalized to creatinine) (Cohorts A and B)
Time Frame: up to 48 weeks
up to 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Denali Therapeutics Inc.

Investigators

  • Study Director: Jose Alcantara Rodriguez, PharmD, Denali Therapeutics Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 21, 2022

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

May 9, 2022

First Submitted That Met QC Criteria

May 9, 2022

First Posted (Actual)

May 12, 2022

Study Record Updates

Last Update Posted (Actual)

September 9, 2026

Last Update Submitted That Met QC Criteria

September 4, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DNLI-E-0007
  • 2024-510990-21-00 (Ctis)
  • 2021-005200-35 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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