Mucopolysaccharidosis IIPhase 2/3NCT06075537
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 study testing tividenofusp alfa in people with Mucopolysaccharidosis II, run by Denali Therapeutics Inc. at 30 sites in 14 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages Up to 18 years
- 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
- 99 participants
- Where
- 30 sitesin 14 countries
- Study dates
- 20 Sep 2023to Jun 2027
- Phase
- Phase 2/3
- 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
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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
Trial locations and contacts
30 sites in 14 countries. Contact the study team or a site near you to ask about taking part.
30 sites in 14 countries
United States8 sites
UNC Children's Research Institute
Chapel Hill, North Carolina, 27599
Ann and Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Hackensack University Medical Center
Hackensack, New Jersey, 07601
The University of Texas Medical School at Houston
Houston, Texas, 77030
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Huntsman Cancer Hospital
Salt Lake City, Utah, 84112
United Kingdom4 sites
Birmingham Women's and Children's NHS Foundation Trust
Birmingham
Royal Free Hospital
London, NW3 2QG
Great Ormond Street Hospital
London, WC1N 3JH
Royal Manchester Children's Hospital
Manchester
Canada3 sites
University of Alberta - Faculty of Medicine & Dentistry
Edmonton, Alberta
McGill University Health Center
Montreal, Quebec, H4A3J1
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Belgium2 sites
Universitair Ziekenhuis Antwerpen
Edegem, Antwerpen, 2650
UZ Brussel
Jette
Germany2 sites
Universitätsklinikum Hamburg-Eppendorf
Hamburg
SpinCS GmbH
Höchheim
Italy2 sites
ASST di Cremona
Cremona
Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Misericordia
Udine
Turkey (Türkiye)2 sites
University Medical Faculty Balcali Hospital
Adana
Gazi Universitesi Tip Fakultes
Ankara
Netherlands1 site
Erasmus Medical Center - Sophia Children's Hospital
Rotterdam, 3015 GD
About this study
Official title: 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.
- Conditions
- Mucopolysaccharidosis II
- Being tested
- tividenofusp alfa
- Keywords
- Hunter Syndrome, MPS II, nMPS II, nnMPS 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 group | Role | What they receive |
|---|---|---|
| Cohort A2 | Experimental | Participants with nMPS II, aged ≥5 to ≤10 years Receives: Drug: tividenofusp alfa |
| Cohort B2 | Experimental | Participants with nMPS II or nnMPS II, aged ≥1 to ≤18 years Receives: Drug: tividenofusp alfa |
| Cohort C2 | Experimental | Participants with nMPS II, aged <4 years Receives: Drug: tividenofusp alfa |
| Cohort D2 | Experimental | Participants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT Receives: Drug: tividenofusp alfa |
| Cohort E2 | Experimental | 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 Receives: Drug: tividenofusp alfa |
| Cohort A7 | Experimental | Participants with nMPS II, aged ≥2 to <6 years Receives: Drug: tividenofusp alfa |
| Cohort B7 | Experimental | Participants with nnMPS II, aged ≥6 to <17 years Receives: Drug: tividenofusp alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and intensity of treatment-emergent adverse events (TEAEs)
Measured: 5 years
Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period
Measured: 5 years
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.
Measured: 5 years
Secondary outcomes (8)
Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration
Measured: 5 years
Change from baseline in the Vineland-3 Adaptive Behavior Scale
Measured: 5 years
Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score
Measured: 5 years
Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT)
Measured: 5 years
Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations
Measured: 5 years
Liver volume within the normal range (normal vs abnormal) as measured by MRI
Measured: 5 years
Spleen volume within the normal range (normal vs abnormal) as measured by MRI
Measured: 5 years
Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2023
- Study start20 Sep 2023
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mucopolysaccharidosis IIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 99 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Denali Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Denali Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06075537
- Sponsor's protocol ID
- DNLI-E-0008
- Other IDs
- 2023-503837-23, 2023
- Status last verified
- Oct 2026
- First submitted
- 18 Sep 2023
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06075537
- Acronym / sponsor ID
- DNLI-E-0008
- Conditions
- Mucopolysaccharidosis II
- Keywords
- Hunter Syndrome, MPS II, nMPS II, nnMPS II
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 99 participants (estimated)
- Lead sponsor
- Denali Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Sep 2023 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 10 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cohort A2 | Experimental | Drug: tividenofusp alfaParticipants with nMPS II, aged ≥5 to ≤10 years |
| Cohort B2 | Experimental | Drug: tividenofusp alfaParticipants with nMPS II or nnMPS II, aged ≥1 to ≤18 years |
| Cohort C2 | Experimental | Drug: tividenofusp alfaParticipants with nMPS II, aged <4 years |
| Cohort D2 | Experimental | Drug: tividenofusp alfaParticipants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT |
| Cohort E2 | Experimental | Drug: tividenofusp alfaParticipants 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 |
| Cohort A7 | Experimental | Drug: tividenofusp alfaParticipants with nMPS II, aged ≥2 to <6 years |
| Cohort B7 | Experimental | Drug: tividenofusp alfaParticipants with nnMPS II, aged ≥6 to <17 years |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- 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 (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tividenofusp alfaIntravenous repeating dose | Drug | Cohort A2, Cohort A7, Cohort B2, Cohort B7, Cohort C2, Cohort D2, Cohort E2 |
Primary outcome
Incidence and intensity of treatment-emergent adverse events (TEAEs)
Time frame: 5 years
Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period
Time frame: 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.
8 secondary outcomes
Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration
Time frame: 5 years
Change from baseline in the Vineland-3 Adaptive Behavior Scale
Time frame: 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
Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT)
Time frame: 5 years
Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations
Time frame: 5 years
Liver volume within the normal range (normal vs abnormal) as measured by MRI
Time frame: 5 years
Spleen volume within the normal range (normal vs abnormal) as measured by MRI
Time frame: 5 years
Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Denali TherapeuticsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Medical Monitor study director
Denali Therapeutics
30 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing tividenofusp alfa in people with Mucopolysaccharidosis II, run by Denali Therapeutics Inc. at 30 sites in 14 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 2 inclusion and 1 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: enrolling by invitation, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, United Kingdom, Canada, Belgium, Germany and 9 more countries. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 intensity of treatment-emergent adverse events (TEAEs) (time frame: 5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Oct 2026.