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Mucopolysaccharidosis IIPhase 1/2NCT04251026

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

A Phase 1/2 study testing tividenofusp alfa in people with Mucopolysaccharidosis II, run by Denali Therapeutics Inc. at 7 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages Up to 18 years, men only
Conditions the study is for
Mucopolysaccharidosis II
What is being tested?
tividenofusp alfa
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
7 sitesin 4 countries
Study dates
16 Jul 2020to Feb 2031
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 18 years
  • Men only
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

7 sites in 4 countries.

7 sites in 4 countries

United States4 sites

  • UNC Children's Research Institute

    Chapel Hill, North Carolina, 27514

  • Ann & Robert H. Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

  • UCSF Benioff Children's Hospital

    Oakland, California, 94609

  • UPMC | Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15224

Other trials in United States

Canada1 site

  • McGill University Health Centre - Royal Victoria Hospital

    Montreal, Quebec, H4A 3J1

Other trials in Canada

Netherlands1 site

  • Erasmus Medical Center

    Rotterdam, South Holland, 3015 GD

Other trials in Netherlands

United Kingdom1 site

  • St Mary's Hospital, Manchester Academic Health Science Centre

    Manchester, M13 9WL

Other trials in United Kingdom

About this study

Official title: A Phase 1/2, Multicenter, Open-Label Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL310 in Pediatric Participants With Hunter Syndrome

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.

Being tested
tividenofusp alfa
Keywords
MPS II, Hunter Syndrome, nMPS II
Medical subject headings
Mucopolysaccharidosis II, Sudden Infant Death

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tividenofusp alfaDrug

    Intravenous repeating dose

Study groups in NCT04251026
Study groupRoleWhat they receive
Cohort AExperimentalDose escalation followed by a consistent dose level in participants with neuronopathic MPS II
Receives: Drug: tividenofusp alfa
Cohort BExperimentalA consistent dose level in participants with non-neuronopathic MPS II, neuronopathic MPS II, or unknown phenotype followed by dose escalation in some participants.
Receives: Drug: tividenofusp alfa
Cohort CExperimentalA consistent dose level in participants with neuronopathic MPS II
Receives: Drug: tividenofusp alfa
Cohort DExperimentalA consistent dose level in participants with non-neuronopathic MPS II or neuronopathic MPS II
Receives: Drug: tividenofusp alfa
Cohort EExperimentalA consistent dose level in participants with non-neuronopathic MPS II or neuronopathic MPS II
Receives: Drug: tividenofusp alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 24 weeks, 104 weeks, and 357 weeks

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

    Measured: 24 weeks, 104 weeks, and 357 weeks

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

    Measured: 24 weeks, 104 weeks, and 357 weeks

  4. Change from baseline in concomitant medications

    Measured: 24 weeks, 104 weeks, and 357 weeks

Secondary outcomes (14)

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

    Measured: 24 weeks

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

    Measured: 49 weeks

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

    Measured: 49 weeks

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

    Measured: 24 weeks

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

    Measured: 24 weeks

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

    Measured: 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

    Measured: 24 weeks

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

    Measured: 24 weeks

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

    Measured: 24 weeks

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

    Measured: 24 weeks

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

    Measured: 24 weeks

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

    Measured: 24 weeks

  13. Participants with liver volume in the normal range

    Measured: 24 weeks and 49 weeks

  14. Percentage change from baseline in liver volume

    Measured: 24 weeks and 49 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2020
  2. Study start16 Jul 2020
  3. Primary completionFeb 2031 (estimated)
  4. Study completionFeb 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04251026
Sponsor's protocol ID
DNLI-E-0002
Other IDs
2023-508619-22-00, 2019-004909-27, 2019, 2023
Status last verified
Aug 2025
First submitted
28 Jan 2020
Last updated
7 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing tividenofusp alfa in people with Mucopolysaccharidosis II, run by Denali Therapeutics Inc. at 7 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, Canada, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of treatment-emergent adverse events (TEAEs) (time frame: 24 weeks, 104 weeks, and 357 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04251026, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2025.

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