Mucopolysaccharidosis Type IIIAPhase 1/2NCT06181136
Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)
A Phase 1/2 study testing DNL126 and Prophylactic immunomodulatory therapy in people with Mucopolysaccharidosis Type IIIA, run by Denali Therapeutics Inc. at 4 sites in United States.
Trial summary
This is a multicenter, open-label, Phase 1/2 study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of DNL126 in participants with Sanfilippo syndrome Type A (MPS IIIA). Read more about this study
- Who is it for?
- Ages 0 to 18 years
- Conditions the study is for
- Mucopolysaccharidosis Type IIIA
- What is being tested?
- DNL126 and Prophylactic immunomodulatory therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 4 sitesUnited States
- Study dates
- 7 Dec 2023to Jul 2032
- 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 0 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Confirmed diagnosis of MPS IIIA
- For Cohorts A2 and C1: No more than 1 participant may have predictors of a slow-progressing phenotype
- For Cohort A3: Approximately 2 participants will have predictors of the slow-progressing phenotype
- For Cohort B1: Have a severe phenotype based on having at least one of the following:
- An older sibling with the same genotype and severe MPS IIIA, in the opinion of the investigator
- A definitive genotype indicative of severe MPS IIIA, in the opinion of the investigator
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- Clinical symptoms of MPS IIIA prior to 28 months of age that, in the opinion of the investigator, are indicative of severe MPS IIIA
- For Cohort B2: Are an older sibling of a participant in Cohort B1 (who has already been confirmed to be eligible for dosing) with MPS IIIA, the same causative genotype, and who has severe MPS IIIA in the opinion of the investigator
- For Cohort C1: Have up-to-date age-specific vaccination status, including SARS-CoV-2 (COVID-19) vaccines, according to country-specific guidelines at the time of the screening visit.
Who cannot join
- Have 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
- Have lost the ability to walk independently, in the opinion of the investigator
- Are unable to take the majority of nutrition via mouth, in the opinion of the investigator
- For Cohort B only: Are homozygous or compound heterozygous for the N-sulfoglucosamine sulfohydrolase (SGSH) S298P mutation or any other mutation known to be associated with slow-progressing phenotype
- Have used any CNS-targeted MPS IIIA enzyme replacement therapy (ERT) (eg, intrathecal SGSH or TfR-mediated SGSH delivery to CNS) within 3 months before Day 1
- Have a prior history of hematopoietic stem cell transplantation
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- Have a prior history of gene therapy
- Have used genistein or anakinra within 7 days of screening or intended use of genistein or anakinra during the study
- Have a documented likely pathogenic mutation sufficient to cause disease (eg, taking into account zygosity) of other genes that are known to be associated with developmental delay, seizures, or other significant CNS disorders
- Have clinically significant thrombocytopenia, other clinically significant coagulation abnormality, significant active bleeding, or require treatment with an anticoagulant or more than two antiplatelet agents
- Contraindication for lumbar punctures
- Contraindication for MRI scan
- Have a clinically significant history of stroke, status epilepticus, head trauma with loss of consciousness, or any clinically significant CNS disease that is not MPS IIIA-related within 3 months of screening
- Have had a ventriculoperitoneal (VP) shunt placed or a clinically significant VP shunt malfunction within 30 days of screening
- Have any clinically significant CNS trauma or disorder, including severe untreated intracranial hypertension or brain surgery, 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
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
Lindsay Torrice, 919-966-1135, Lindsay_torrice@med.unc.edu
- Recruiting
Baylor College of Medicine and Texas Children's Hospital
Houston, Texas, 77030
Varsha Yallamanchi, 832-824-3323, varsha.yallamanchi@bcm.edu
Katherine Ann Asuncion, 832-824-1421, KatherineAnn.Asuncion@bcm.edu
- Recruiting
University of Iowa Stead Family Children's Hospital
Iowa City, Iowa, 52242
Lauren VanOpdorp, 319-467-8197, lauren-vanopdorp@uiowa.edu
- Recruiting
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Ivy Lee Hung, 510-428-3885 ext. 5156, Ivy.LeeHung@ucsf.edu
About this study
Official title: A Phase 1/2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)
This is a multicenter, open-label, Phase 1/2 study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of DNL126 in participants with Sanfilippo syndrome Type A (MPS IIIA). In Part 1, the core study period is 25 weeks (approximately 6 months); followed by an open-label extension (OLE), which extends through Week 97 (approximately 18 months); and a long-term extension (LTE), which extends through Week 241 (Year 5). In Part 2, the core study period is 25 weeks in duration followed by an OLE, which extends through Week 49, and an LTE, which extends through Week 241 (Year 5). Participants with MPS IIIA will be enrolled in three planned cohorts, and additional participants with MPS IIIA may be enrolled in three optional cohorts.
The study will enroll up to approximately 30 participants in total: 26 participants in Part 1 (Cohorts A1, A2, A3, B1, and B2 - not enrolling) and 4 participants in Part 2 (Cohort C1 - actively enrolling).
- Conditions
- Mucopolysaccharidosis Type IIIA
- Being tested
- DNL126, Prophylactic immunomodulatory therapy
- Keywords
- Sanfilippo Syndrome, MPS IIIA
- Medical subject headings
- Mucopolysaccharidosis III
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNL126Drug
intravenous repeating dose
Prophylactic immunomodulatory therapyDrug
Per local prescribing information
| Study group | Role | What they receive |
|---|---|---|
| Cohort A1 | Experimental | Participants with MPS IIIA Receives: Drug: DNL126 |
| Cohort A2 | Experimental | Participants with MPS IIIA Receives: Drug: DNL126 |
| Cohort A3 | Experimental | Participants with MPS IIIA Receives: Drug: DNL126 |
| Cohort B1 | Experimental | Participants with MPS IIIA Receives: Drug: DNL126 |
| Cohort B2 | Experimental | Participants with MPS IIIA Receives: Drug: DNL126 |
| Cohort C1 | Experimental | Participants with MPS IIIA Receives: Drug: DNL126; Drug: Prophylactic immunomodulatory therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Change from baseline in the natural logarithm of cerebrospinal fluid (CSF) heparan sulfate (HS) concentration
Measured: 49 weeks
Secondary outcomes (4)
Part 1: Change from baseline in the natural logarithm of urine HS (normalized to creatinine) concentration
Measured: 49 weeks
Part 1: Change from baseline in liver volume multiples of normal
Measured: 49 weeks
Part 1: Change from baseline in the natural logarithm of serum neurofilament light chain (NfL) concentration
Measured: 73 weeks
Part 1: Participants with CSF HS concentration within the normal range
Measured: 49 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2023
- Study start7 Dec 2023
- Primary completionJul 2032 (estimated)
- Study completionJul 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mucopolysaccharidosis Type IIIAStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Denali Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ana-Claire Meyer, MD, Study director, Denali Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06181136
- Sponsor's protocol ID
- DNLI-I-0001
- Status last verified
- Oct 2026
- First submitted
- 4 Dec 2023
- Last updated
- 2 Nov 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 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)
- ClinicalTrials.gov ID
- NCT06181136
- Acronym / sponsor ID
- DNLI-I-0001
- Conditions
- Mucopolysaccharidosis Type IIIA
- Keywords
- Sanfilippo Syndrome, MPS IIIA
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Denali Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 7 Dec 2023 (actual)
- Primary completion
- Jul 2032 (estimated)
- Study completion
- Jul 2032 (estimated)
- First posted
- 26 Dec 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 multicenter, open-label, Phase 1/2 study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of DNL126 in participants with Sanfilippo syndrome Type A (MPS IIIA). In Part 1, the core study period is 25 weeks (approximately 6 months); followed by an open-label extension (OLE), which extends through Week 97 (approximately 18 months); and a long-term extension (LTE), which extends through Week 241 (Year 5). In Part 2, the core study period is 25 weeks in duration followed by an OLE, which extends through Week 49, and an LTE, which extends through Week 241 (Year 5). Participants with MPS IIIA will be enrolled in three planned cohorts, and additional participants with MPS IIIA may be enrolled in three optional cohorts.
The study will enroll up to approximately 30 participants in total: 26 participants in Part 1 (Cohorts A1, A2, A3, B1, and B2 - not enrolling) and 4 participants in Part 2 (Cohort C1 - actively enrolling).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort A1 | Experimental | Drug: DNL126Participants with MPS IIIA |
| Cohort A2 | Experimental | Drug: DNL126Participants with MPS IIIA |
| Cohort A3 | Experimental | Drug: DNL126Participants with MPS IIIA |
| Cohort B1 | Experimental | Drug: DNL126Participants with MPS IIIA |
| Cohort B2 | Experimental | Drug: DNL126Participants with MPS IIIA |
| Cohort C1 | Experimental | Drug: DNL126, Drug: Prophylactic immunomodulatory therapyParticipants with MPS IIIA |
Who may qualify
- Ages
- 0 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Confirmed diagnosis of MPS IIIA
- For Cohorts A2 and C1: No more than 1 participant may have predictors of a slow-progressing phenotype
- For Cohort A3: Approximately 2 participants will have predictors of the slow-progressing phenotype
- For Cohort B1: Have a severe phenotype based on having at least one of the following:
- For Cohort B2: Are an older sibling of a participant in Cohort B1 (who has already been confirmed to be eligible for dosing) with MPS IIIA, the same causative genotype, and who has severe MPS IIIA in the opinion of the investigator
Key exclusion criteria (15 listed)
- Have 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
- Have lost the ability to walk independently, in the opinion of the investigator
- Are unable to take the majority of nutrition via mouth, in the opinion of the investigator
- For Cohort B only: Are homozygous or compound heterozygous for the N-sulfoglucosamine sulfohydrolase (SGSH) S298P mutation or any other mutation known to be associated with slow-progressing phenotype
- Have used any CNS-targeted MPS IIIA enzyme replacement therapy (ERT) (eg, intrathecal SGSH or TfR-mediated SGSH delivery to CNS) within 3 months before Day 1
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 |
|---|---|---|
| DNL126intravenous repeating dose | Drug | Cohort A1, Cohort A2, Cohort A3, Cohort B1, Cohort B2, Cohort C1 |
| Prophylactic immunomodulatory therapyPer local prescribing information | Drug | Cohort C1 |
Primary outcome
Part 1: Change from baseline in the natural logarithm of cerebrospinal fluid (CSF) heparan sulfate (HS) concentration
Time frame: 49 weeks
4 secondary outcomes
Part 1: Change from baseline in the natural logarithm of urine HS (normalized to creatinine) concentration
Time frame: 49 weeks
Part 1: Change from baseline in liver volume multiples of normal
Time frame: 49 weeks
Part 1: Change from baseline in the natural logarithm of serum neurofilament light chain (NfL) concentration
Time frame: 73 weeks
Part 1: Participants with CSF HS concentration within the normal range
Time frame: 49 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 2 Nov 2026.
- Individual participant dataSharing planned: No
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Single Injection of rAAV9-CMV-hNAGLUop Gene for Patients With Mucopolysaccharidosis (MPS) IIIB
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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.
Ana-Claire Meyer, MD study director
Denali Therapeutics
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DNL126 and Prophylactic immunomodulatory therapy in people with Mucopolysaccharidosis Type IIIA, run by Denali Therapeutics Inc. at 4 sites in United States.
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 9 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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?
Contact Clinical Trials at Denali Therapeutics (Email, clinical-trials@dnli.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Change from baseline in the natural logarithm of cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (time frame: 49 weeks). 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 2 Nov 2026.