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NCT Number: NCT05371613

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)

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.

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Key information

Conditions

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

Age range

2 year–25 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Sanatorio Mater Dei, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

tividenofusp alfa

Drug

Intravenous repeating dose

idursulfase

Drug

Intravenous repeating dose

Primary outcomes

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

    Time frame: 24 weeks

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

    Time frame: 96 weeks

Secondary outcomes

  1. Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)(Cohort A only)

    Time frame: 96 weeks

  2. Change from baseline in the Vineland-3 Adaptive Behavior Composite (ABC; Cohort A only)

    Time frame: 96 weeks

  3. Change from baseline in serum neurofilament light chain (NfL) (Cohort A only)

    Time frame: 96 weeks

  4. Change from baseline in distance walked in the Six-Minute Walk Test (6MWT; Cohort B only)

    Time frame: 48 weeks

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

    Time frame: up to 48 weeks

  6. Liver volume within the normal range (normal vs abnormal) as measured by magnetic resonance imaging (MRI) (Cohorts A and B)

    Time frame: 48 weeks

  7. Spleen volume within the normal range (normal vs abnormal) as measured by MRI (Cohorts A and B)

    Time frame: 48 weeks

  8. Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B)

    Time frame: 48 weeks

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trials at Denali Therapeutics

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Denali Therapeutics Inc.

Industry

Registry information

Official study title

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

Acronym: COMPASS

Important dates

Study start
2022
Primary completion
2027
Study completion
2027
First posted
May 12, 2022
Registry last updated
Aug 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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