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

June 9, 2026 updated by: Denali Therapeutics Inc.

An Open-Label Extension to Investigate the Long-Term Safety, Tolerability, and Efficacy of DNL310 in Patients With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
99

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Sanatorio Mater Dei
  • Belgium
      • Jette, Belgium
        • UZ Brussel
    • Antwerpen
      • Edegem, Antwerpen, Belgium, 2650
        • Universitair Ziekenhuis Antwerpen
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada
        • University of Alberta - Faculty of Medicine & Dentistry
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H4A3J1
        • McGill University Health Center
  • Czechia
      • Prague, Czechia, 120 00
        • Vseobecna fakultni nemocnice v Praze
  • France
      • Lille, France
        • Hopital Jeanne De Flandre - Metabolic Diseases Unit
  • Germany
      • Hamburg, Germany
        • Universitätsklinikum Hamburg-Eppendorf
      • Höchheim, Germany
        • SpinCS GmbH
  • Italy
      • Cremona, Italy
        • Asst Di Cremona
      • Udine, Italy
        • Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Misericordia
  • Netherlands
      • Rotterdam, Netherlands, 3015 GD
        • Erasmus Medical Center - Sophia Children's Hospital
  • Spain
      • Barcelona, Spain
        • Hospit U. Vall d'Hebron - PPDS
  • Sweden
      • Gothenburg, Sweden
        • Drottning Silvias Barn Och Ungdomssjukhus
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye)
        • University Medical Faculty Balcali Hospital
      • Ankara, Turkey (Türkiye)
        • Gazi Universitesi Tip Fakultes
  • United Kingdom
      • Birmingham, United Kingdom
        • Birmingham Women's and Children's NHS Foundation Trust
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital
      • London, United Kingdom, WC1N 3JH
        • Great Ormond Street Hospital
      • Manchester, United Kingdom
        • Royal Manchester Children's Hospital
  • 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, 27599
        • 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, 84112
        • Huntsman Cancer Hospital

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort A2
Participants with nMPS II, aged ≥5 to ≤10 years
Drug: tividenofusp alfa
Intravenous repeating dose
Experimental: Cohort B2
Participants with nMPS II or nnMPS II, aged ≥1 to ≤18 years
Drug: tividenofusp alfa
Intravenous repeating dose
Experimental: Cohort C2
Participants with nMPS II, aged <4 years
Drug: tividenofusp alfa
Intravenous repeating dose
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
Intravenous repeating dose
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
Intravenous repeating dose
Experimental: Cohort A7
Participants with nMPS II, aged ≥2 to <6 years
Drug: tividenofusp alfa
Intravenous repeating dose
Experimental: Cohort B7
Participants with nnMPS II, aged ≥6 to <17 years
Drug: tividenofusp alfa
Intravenous repeating dose

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence and intensity of treatment-emergent adverse events (TEAEs)
Time Frame: 5 years
5 years
Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period
Time Frame: 5 years
5 years
Incidence and intensity of infusion-related reactions (IRRs)
Time Frame: 5 years
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.
5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration
Time Frame: 5 years
5 years
Change from baseline in the Vineland-3 Adaptive Behavior Scale
Time Frame: 5 years
5 years
Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score
Time Frame: 5 years
5 years
Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT)
Time Frame: 5 years
5 years
Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations
Time Frame: 5 years
5 years
Liver volume within the normal range (normal vs abnormal) as measured by MRI
Time Frame: 5 years
5 years
Spleen volume within the normal range (normal vs abnormal) as measured by MRI
Time Frame: 5 years
5 years
Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II
Time Frame: 5 years
5 years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Denali Therapeutics Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Monitor, Denali Therapeutics

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 20, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 18, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 3, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 10, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 11, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DNLI-E-0008
  • 2023-503837-23 (Other Identifier: EU Trial 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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