ClinicalTrials.gg
Enrolling by invitationNCT06075537Updated Nov 9, 2026

An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of Tividenofusp Alfa (DNL310) in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007

A Phase 2/3 interventional study of tividenofusp alfa in Mucopolysaccharidosis II, sponsored by Denali Therapeutics Inc.. Enrolling by invitation at 31 sites in 14 countries. Open to participants aged Up to 18 Years. Per ClinicalTrials.gov, last updated 2026-11-09.

Sponsored by Denali Therapeutics Inc. · Phase 2/3, Interventional, and Treatment

Updated Nov 9, 2026First site in Brazil2 sites addedGo to Updates ↓
Phase
Phase 2/3
Study type
Interventional
Enrollment
99
Allocation
Non-randomized
Ages
Up to 18 Years
Sex
All
01

Study summary

This is a multiregional open-label extension (OLE) to assess the safety, tolerability, and efficacy of long-term treatment with tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant intravenous (IV) enzyme replacement therapy (ERT) for Hunter syndrome (MPS II). Participants who complete at least through the Week 49 visit in Study DNLI-E-0002 and do not discontinue study intervention early and participants who complete Study DNLI-E-0007 will be enrolled in this OLE. All participants will receive DNL310 for up to 5 years from the time of entry in this OLE. Participants, site staff, and the Sponsor will remain blinded to the original treatment assignment for participants entering this OLE from Study DNLI-E-0007.

02

Conditions studied

  • Mucopolysaccharidosis II

Keywords

  • Hunter Syndrome
  • MPS II
  • nMPS II
  • nnMPS II
03

In context

Mucopolysaccharidosis II

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

This study's planned enrollment of 99 is above the median of 22 across 48 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; 5 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
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  • For participants from Study DNLI-E-0002 only: Completed at least through the Week 49 visit in Study DNLI-E-0002 and did not discontinue study intervention early
  • For participants from Study DNLI-E-0007 only: Completed the treatment period of 96 weeks in Cohort A for nMPS II participants and 48 weeks in Cohort B for nnMPS II participants

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
05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
99 participants (estimated)

Study arms

  • Experimental
    Cohort A2

    Participants with nMPS II, aged ≥5 to ≤10 years

    Drug: tividenofusp alfa

  • Experimental
    Cohort B2

    Participants with nMPS II or nnMPS II, aged ≥1 to ≤18 years

    Drug: tividenofusp alfa

  • Experimental
    Cohort C2

    Participants with nMPS II, aged \<4 years

    Drug: tividenofusp alfa

  • Experimental
    Cohort D2

    Participants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT

    Drug: tividenofusp alfa

  • Experimental
    Cohort E2

    Participants with nMPS II, aged ≥6 years; participants with nnMPS II, aged \<6 or ≥17 years; or participants with nMPS II, aged ≥1 to ≤18 years, with a history of prior HSCT or gene therapy and have completed at least 48 weeks in Study DNLI-E-0001

    Drug: tividenofusp alfa

  • Experimental
    Cohort A7

    Participants with nMPS II, aged ≥2 to \<6 years

    Drug: tividenofusp alfa

  • Experimental
    Cohort B7

    Participants with nnMPS II, aged ≥6 to \<17 years

    Drug: tividenofusp alfa

Interventions

06

What researchers measure

Primary outcomes

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

    Time frame: 5 years

  2. Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period

    Time frame: 5 years

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

    The intensity of IRRs will be assessed following each infusion of DNL310 using the categories of Mild, Moderate and Severe. IRRs will be summarized overall as well as stratified by intensity.

    Time frame: 5 years

Secondary outcomes

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

    Time frame: 5 years

  2. Change from baseline in the Vineland-3 Adaptive Behavior Scale

    Time frame: 5 years

  3. Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score

    Time frame: 5 years

  4. Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT)

    Time frame: 5 years

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

    Time frame: 5 years

  6. Liver volume within the normal range (normal vs abnormal) as measured by MRI

    Time frame: 5 years

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

    Time frame: 5 years

  8. Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II

    Time frame: 5 years

07

Study locations

31 sites
08

References and documents

Individual participant data

Plan to share: No

09

Updates

2 registry updates since Sep 25, 2026
Sites
2 sites added — first site in Brazil
Show 2 added (1 Brazil, 1 United Kingdom)
  • Hospital Clinicas Porto Alegre · Porto Alegre, Brazil
  • Salford Royal Hospital · Salford, United Kingdom
across 2 updates, Oct 27, 2026 – Nov 9, 2026
Show all 2 updates
  1. Nov 9, 2026
    1 site added
    Show site
    • Salford Royal Hospital · Salford, United Kingdom
    + 1 other change: verification date
  2. Oct 27, 2026
    1 site added — first site in Brazil
    Show site
    • Hospital Clinicas Porto Alegre · Porto Alegre, Brazil
    + 2 other changes: identifiers and verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT06075537
Lead sponsor
Denali Therapeutics Inc.
Responsible party
Sponsor
First posted
Oct 10, 2023
Start date
Sep 20, 2023
Primary completion
Jun 2027 (estimated)
Completion
Jun 2027 (estimated)
Last update
Nov 9, 2026

Study contacts

Medical Monitor
study director · Denali Therapeutics

Oversight

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

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

No contact was published for this record. The registry link below has the sponsor’s details.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Tividenofusp alfa

Start the discussion