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Active, not recruitingNCT04251026Updated Aug 7, 2025

A Study of Tividenofusp Alfa (DNL310) in Pediatric Participants With Hunter Syndrome

A Phase 1/2 interventional study of tividenofusp alfa in Mucopolysaccharidosis II, sponsored by Denali Therapeutics Inc.. Active, not recruiting at 7 sites in 4 countries. Open to male participants aged Up to 18 Years. Per ClinicalTrials.gov, last updated 2025-08-07.

Sponsored by Denali Therapeutics Inc. · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
47
Allocation
Non-randomized
Ages
Up to 18 Years
Sex
Male
01

Study summary

This is a multicenter, multiregional, open-label study to assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant enzyme replacement therapy (ERT), designed to treat both the peripheral and CNS manifestations of Mucopolysaccharidosis type II (MPS II; Hunter syndrome).

Participants, whose physicians feel they are deriving benefit, will have the opportunity to be reconsented into a safety extension and then an open-label extension for continued evaluation.

02

Conditions studied

  • Mucopolysaccharidosis II

Keywords

  • MPS II
  • Hunter Syndrome
  • nMPS II
03

In context

Mucopolysaccharidosis II

71 studies on the registry are indexed under Mucopolysaccharidosis II; 8 are open to participants now.

This study's enrollment of 47 is above the median of 20 across 43 interventional studies indexed under Mucopolysaccharidosis II.

Browse Mucopolysaccharidosis II studies →

Lead sponsor

Denali Therapeutics Inc. is the lead sponsor of 19 studies on the registry; 4 are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 18 Years
Sexes eligible
Male
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  • Confirmed diagnosis of MPS II
  • Cohort A: Participants aged ≥5 to ≤10 years with neuronopathic MPS II
  • Cohort B: Participants aged ≥1 to ≤18 years with non-neuronopathic MPS II, neuronopathic MPS II, or unknown phenotype
  • Cohort C: Participants aged \<4 years with neuronopathic MPS II (this cohort can include participants ≥4 to ≤18 years of age if participant is a blood relative of a participant \<4 years of age)
  • Cohort D: Participants aged ≤18 years with non-neuronopathic MPS II or neuronopathic MPS II with preexisting hepatomegaly who have never taken standard-of-care ERT
  • Cohort E: neuronopathic MPS II participants aged ≥6 years at screening, non-neuronopathic MPS II participants \<6 or ≥17 years at screening, and neuronopathic MPS II participants ≥1 to ≤18 years at screening with a history of prior haematopoietic stem cell transplantation or gene therapy who have completed at least 48 weeks in Study DNLI-E-0001
  • For participants receiving intravenous iduronate 2-sulfatase (IDS) ERT, tolerated a minimum of 4 months of therapy during the period immediately prior to screening.

Key Exclusion Criteria:

  • Unstable or poorly controlled medical condition(s) or significant medical or psychological comorbidity or comorbidities that, in the opinion of the investigator, would interfere with safe participation in the trial or interpretation of study assessments
  • Use of any CNS-targeted MPS II ERT within 3 months before study start for participants aged ≥5 years, and within 6 months before study start for participants aged \<5 years
  • Use of IDS gene therapy or stem cell therapy at any time (except for participants in Cohort E)
  • Clinically significant thrombocytopenia, other clinically significant coagulation abnormality, or significant active bleeding, or required treatment with an anticoagulant or more than two antiplatelet agents
  • Contraindication for lumbar punctures
  • Have a clinically significant history of stroke, status epilepticus, head trauma with loss of consciousness, or any CNS disease that is not MPS II-related within 1 year of screening
  • Have had a ventriculoperitoneal (VP) shunt placed, or any other brain surgery, or have a clinically significant VP shunt malfunction within 30 days of screening
  • Have any clinically significant CNS trauma or disorder that, in the opinion of the investigator, may interfere with assessment of study endpoints or make participation in the study unsafe
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
47 participants (actual)

Study arms

  • Experimental
    Cohort A

    Dose escalation followed by a consistent dose level in participants with neuronopathic MPS II

    Drug: tividenofusp alfa

  • Experimental
    Cohort B

    A consistent dose level in participants with non-neuronopathic MPS II, neuronopathic MPS II, or unknown phenotype followed by dose escalation in some participants.

    Drug: tividenofusp alfa

  • Experimental
    Cohort C

    A consistent dose level in participants with neuronopathic MPS II

    Drug: tividenofusp alfa

  • Experimental
    Cohort D

    A consistent dose level in participants with non-neuronopathic MPS II or neuronopathic MPS II

    Drug: tividenofusp alfa

  • Experimental
    Cohort E

    A consistent dose level in participants with non-neuronopathic MPS II or neuronopathic MPS II

    Drug: tividenofusp alfa

Interventions

  • Drugtividenofusp alfa

    Intravenous repeating dose

06

What researchers measure

Primary outcomes

  1. Incidence and severity of treatment-emergent adverse events (TEAEs)

    Time frame: 24 weeks, 104 weeks, and 357 weeks

  2. Change from baseline in urine total glycosaminoglycan (GAG) concentrations

    Time frame: 24 weeks, 104 weeks, and 357 weeks

  3. Incidence and severity of infusion-related reactions (IRRs)

    Time frame: 24 weeks, 104 weeks, and 357 weeks

  4. Change from baseline in concomitant medications

    Time frame: 24 weeks, 104 weeks, and 357 weeks

Secondary outcomes

  1. Percentage change from baseline in cerebrospinal fluid (CSF) of heparan sulfate

    Time frame: 24 weeks

  2. Participants with improvement in individual disease progression in the Vineland Adaptive Behavior Scale Adaptive Behavior Composite (ABC) score

    Time frame: 49 weeks

  3. Participants with improvement in individual disease progression in the Vineland Adaptive Behavior Scale subdomain scores

    Time frame: 49 weeks

  4. PK parameter: Maximum observed concentration (Cmax) of DNL310 in serum

    Time frame: 24 weeks

  5. PK parameter: Trough concentration (Cmin) of DNL310 in serum

    Time frame: 24 weeks

  6. PK parameter: Time to maximum observed concentration (tmax) of DNL310 in serum

    Time frame: 24 weeks

  7. PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of DNL310 in serum

    Time frame: 24 weeks

  8. PK parameter: Area under the concentration-time curve from time zero to infinity (AUC∞) of DNL310 in serum

    Time frame: 24 weeks

  9. PK parameter: Area under the concentration-time curve over a dosing interval (AUCτ) of DNL310 in serum

    Time frame: 24 weeks

  10. PK parameter: Apparent terminal elimination half-life (t½) of DNL310 in serum

    Time frame: 24 weeks

  11. Characterization of immunogenicity of DNL310 in serum, as measured by the incidence of anti-drug antibodies (ADAs) relative to baseline

    Time frame: 24 weeks

  12. Percent change from baseline in urine concentration of heparan sulfate (HS)

    Time frame: 24 weeks

  13. Participants with liver volume in the normal range

    Time frame: 24 weeks and 49 weeks

  14. Percentage change from baseline in liver volume

    Time frame: 24 weeks and 49 weeks

07

Study locations

7 sites
  • UCSF Benioff Children's Hospital
    Oakland, California 94609, United States
  • Ann & Robert H. Lurie Children's Hospital of Chicago
    Chicago, Illinois 60611, United States
  • UNC Children's Research Institute
    Chapel Hill, North Carolina 27514, United States
  • UPMC | Children's Hospital of Pittsburgh
    Pittsburgh, Pennsylvania 15224, United States
  • McGill University Health Centre - Royal Victoria Hospital
    Montreal, Quebec H4A 3J1, Canada
  • Erasmus Medical Center
    Rotterdam, South Holland 3015 GD, Netherlands
  • St Mary's Hospital, Manchester Academic Health Science Centre
    Manchester, M13 9WL, United Kingdom
08

References and documents

Publications

  • Muenzer J, Burton BK, Harmatz P, Rajan DS, Jones SA, van den Hout JMP, Mitchell JJ, Bhalla A, Engmann NJ, Zubizarreta I, Dong W, Model F, Watts RJ, Troyer MD, Chin PS, Ho C. An Intravenous Brain-Penetrant Enzyme Therapy for Mucopolysaccharidosis II. N Engl J Med. 2026 Jan 1;394(1):39-50. doi: 10.1056/NEJMoa2508681. PubMed 41467650 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 7, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04251026
Lead sponsor
Denali Therapeutics Inc.
Responsible party
Sponsor
First posted
Jan 31, 2020
Start date
Jul 16, 2020
Primary completion
Feb 2031 (estimated)
Completion
Feb 2031 (estimated)
Last update
Aug 7, 2025

Study contacts

Sam Lu, MD
study director · Denali Therapeutics

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is active, not recruiting, as verified in Aug 2025. You cannot join it, but the record below documents what was studied.

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