Mucopolysaccharidosis IIPhase 2/3COMPASSNCT05371613
A Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II)
A Phase 2/3 study testing tividenofusp alfa and idursulfase in people with Mucopolysaccharidosis II, run by Denali Therapeutics Inc. at 30 sites in 14 countries.
Trial summary
This is a Phase 2/3, multiregional, two-arm, double-blind, randomized, active (standard-of-care)-controlled study of the efficacy and safety of tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant enzyme-replacement therapy (ERT) for mucopolysaccharidosis type II (MPS II). Read more about this study
- Who is it for?
- Ages 2 to 25 years
- Conditions the study is for
- Mucopolysaccharidosis II
- What is being tested?
- tividenofusp alfa and idursulfase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 30 sitesin 14 countries
- Study dates
- 21 Jul 2022to Dec 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 2 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participants aged ≥2 to <6 years (Cohort A) or ≥6 to <26 years (Cohort B)
- Confirmed diagnosis of MPS II (for Cohort A, nMPS II; for Cohort B, nnMPS II)
- Have no history of treatment with enzyme replacement therapy (ERT) OR not have received continuous ERT for 4 months prior to screening OR be on maintenance ERT and have tolerated idursulfase for a minimum of 4 months prior to screening
Who cannot join
- Have a documented mutation of other genes or genetic diagnosis accounting for developmental delay
- Previously received an iduronate 2-sulfatase (IDS) gene therapy or stem cell therapy
- Received any CNS-targeted MPS ERT within 6 months prior to screening
- Have a contraindication for lumbar punctures and/or magnetic resonance imaging (MRI)
- Participated in any other investigational drug study or used an investigational drug within 60 days prior to screening or intend to receive another investigational drug during the study
Trial locations and contacts
30 sites in 14 countries.
30 sites in 14 countries
United States8 sites
UNC Children's Research Institute
Chapel Hill, North Carolina, 27514
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
University of Utah, PPDS
Salt Lake City, Utah, 84132
United Kingdom4 sites
Birmingham Women's and Children's NHS Foundation Trust
Birmingham
Great Ormond Street Hospital for Children
London, London, WC1N 3JH
Royal Free Hospital
London, NW3 2QG
Salford Royal Hospital
Salford, M6 8HD
Canada3 sites
University of Alberta - Faculty of Medicine & Dentistry
Edmonton, Alberta
McGill University Health Center
Montreal, Quebec, H4A3J1
Hospital for Sick Children
Toronto, Ontario, M5G1X8
Belgium2 sites
UZ Antwerpen
Antwerp, Antwerpen, 2650
Universitair Ziekenhuis Brussel
Jette, Brussels Capital, 1090
Germany2 sites
Medizinische Universität Lausitz - Carl Thiem
Cottbus
SphinCS
Höchheim, Hochheim, 65239
Spain2 sites
Hospital Universitario Vall d'Hebron
Barcelona, Barcelona, 08035
Hospital Infantil Universitario Niño Jesus
Madrid, Madrid, 28009
Turkey (Türkiye)2 sites
Cukurova University Medical Faculty Balcali Hospital
Adana, 1330
Gazi Universitesi Tip Fakultesi
Çankaya, 06500
Italy1 site
Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Misericordia
Udine, 33100
Netherlands1 site
Erasmus Medical Center - Sophia Children's Hospital
Rotterdam, Rotterdam, 3000
About this study
Official title: A Phase 2/3, Multicenter, Double-Blind, Randomized Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic or Non-Neuronopathic Mucopolysaccharidosis Type II
This is a Phase 2/3, multiregional, two-arm, double-blind, randomized, active (standard-of-care)-controlled study of the efficacy and safety of tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant enzyme-replacement therapy (ERT) for mucopolysaccharidosis type II (MPS II).
Participants may also qualify to enter an open-label treatment phase with DNL310 or idursulfase based on pre-specified criteria.
- Conditions
- Mucopolysaccharidosis II
- Being tested
- tividenofusp alfa, idursulfase
- 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
idursulfaseDrug
Intravenous repeating dose
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: Participants with nMPS II | Experimental | Not described Receives: Drug: tividenofusp alfa; Drug: idursulfase |
| Cohort B: Participants with nnMPS II | Experimental | Not described Receives: Drug: tividenofusp alfa; Drug: idursulfase |
| Open-label Treatment Phase | Experimental | Participants who meet pre-specified criteria may receive DNL310 or idursulfase Receives: Drug: tividenofusp alfa; Drug: idursulfase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio to baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A)
Measured: 24 weeks
Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A)
Measured: 96 weeks
Secondary outcomes (8)
Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)(Cohort A only)
Measured: 96 weeks
Change from baseline in the Vineland-3 Adaptive Behavior Composite (ABC) score (Cohort A only)
Measured: 96 weeks
Ratio to baseline in serum neurofilament light chain (NfL) (Cohort A only)
Measured: 96 weeks
Change from baseline in distance walked in the Six-Minute Walk Test (6MWT; Cohort B only)
Measured: 48 weeks
Ratio to baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (normalized to creatinine) (Cohorts A and B)
Measured: up to 48 weeks
Liver volume within the normal range (normal vs abnormal) as measured by magnetic resonance imaging (MRI) (Cohorts A and B)
Measured: 48 weeks
Spleen volume within the normal range (normal vs abnormal) as measured by MRI (Cohorts A and B)
Measured: 48 weeks
Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B)
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2022
- Study start21 Jul 2022
- Primary completionDec 2027 (estimated)
- Study completionDec 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Denali Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jose Alcantara Rodriguez, PharmD, Study director, Denali Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05371613
- Sponsor's protocol ID
- DNLI-E-0007
- Other IDs
- 2024-510990-21-00, 2021-005200-35
- Acronym
- COMPASS
- Status last verified
- Sep 2026
- First submitted
- 9 May 2022
- Last updated
- 9 Sep 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 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2/3, Multicenter, Double-Blind, Randomized Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic or Non-Neuronopathic Mucopolysaccharidosis Type II
- ClinicalTrials.gov ID
- NCT05371613
- Acronym / sponsor ID
- COMPASS / DNLI-E-0007
- Conditions
- Mucopolysaccharidosis II
- Keywords
- Hunter Syndrome, MPS II, nMPS II, nnMPS II
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Denali Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 21 Jul 2022 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 12 May 2022 (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 Phase 2/3, multiregional, two-arm, double-blind, randomized, active (standard-of-care)-controlled study of the efficacy and safety of tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant enzyme-replacement therapy (ERT) for mucopolysaccharidosis type II (MPS II).
Participants may also qualify to enter an open-label treatment phase with DNL310 or idursulfase based on pre-specified criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Participants with nMPS II | Experimental | Drug: tividenofusp alfa, Drug: idursulfase |
| Cohort B: Participants with nnMPS II | Experimental | Drug: tividenofusp alfa, Drug: idursulfase |
| Open-label Treatment Phase | Experimental | Drug: tividenofusp alfa, Drug: idursulfaseParticipants who meet pre-specified criteria may receive DNL310 or idursulfase |
Who may qualify
- Ages
- 2 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Participants aged ≥2 to <6 years (Cohort A) or ≥6 to <26 years (Cohort B)
- Confirmed diagnosis of MPS II (for Cohort A, nMPS II; for Cohort B, nnMPS II)
- Have no history of treatment with enzyme replacement therapy (ERT) OR not have received continuous ERT for 4 months prior to screening OR be on maintenance ERT and have tolerated idursulfase for a minimum of 4 months prior to screening
Key exclusion criteria (5 listed)
- Have a documented mutation of other genes or genetic diagnosis accounting for developmental delay
- Previously received an iduronate 2-sulfatase (IDS) gene therapy or stem cell therapy
- Received any CNS-targeted MPS ERT within 6 months prior to screening
- Have a contraindication for lumbar punctures and/or magnetic resonance imaging (MRI)
- Participated in any other investigational drug study or used an investigational drug within 60 days prior to screening or intend to receive another investigational drug during the study
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 A: Participants with nMPS II, Cohort B: Participants with nnMPS II, Open-label Treatment Phase |
| idursulfaseIntravenous repeating dose | Drug | Cohort A: Participants with nMPS II, Cohort B: Participants with nnMPS II, Open-label Treatment Phase |
Primary outcome
Ratio to baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A)
Time frame: 24 weeks
Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A)
Time frame: 96 weeks
8 secondary outcomes
Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)(Cohort A only)
Time frame: 96 weeks
Change from baseline in the Vineland-3 Adaptive Behavior Composite (ABC) score (Cohort A only)
Time frame: 96 weeks
Ratio to baseline in serum neurofilament light chain (NfL) (Cohort A only)
Time frame: 96 weeks
Change from baseline in distance walked in the Six-Minute Walk Test (6MWT; Cohort B only)
Time frame: 48 weeks
Ratio to baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (normalized to creatinine) (Cohorts A and B)
Time frame: up to 48 weeks
Liver volume within the normal range (normal vs abnormal) as measured by magnetic resonance imaging (MRI) (Cohorts A and B)
Time frame: 48 weeks
Spleen volume within the normal range (normal vs abnormal) as measured by MRI (Cohorts A and B)
Time frame: 48 weeks
Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B)
Time frame: 48 weeks
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 9 Sep 2026.
- Denali TherapeuticsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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
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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. This study is not recruiting at the moment.
Jose Alcantara Rodriguez, PharmD study director
Denali Therapeutics Inc.
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 and idursulfase 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 3 inclusion and 5 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 9 Sep 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?
Ratio to baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A) (time frame: 24 weeks). The study lists 2 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 9 Sep 2026.