Recruiting

Phase 1

Phase 2

DNL126Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)

Sponsor:

Denali Therapeutics Inc.

Code:

NCT06181136

Conditions

Mucopolysaccharidosis Type IIIA

Eligibility Criteria

Sex: All

Age: 0 - 18

Healthy Volunteers: Not accepted

Interventions

DNL126

Prophylactic immunomodulatory therapy

Study Details

Brief 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). 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

Study ID

NCT06181136

Start date

Dec 7, 2023

Status verified date

Oct, 2026

Completion date

Jul, 2032

Anticipated

Primary completion date

Jul, 2032

Anticipated

Eligibility Criteria

Sex: All

Age: 0 - 18

Healthy Volunteers: Not accepted

Key Inclusion Criteria:

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
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.

Key Exclusion Criteria:

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
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

Study Design

Enrollment

30 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort A1

Participants with MPS IIIA

experimental: Cohort A2

Participants with MPS IIIA

experimental: Cohort A3

Participants with MPS IIIA

experimental: Cohort B1

Participants with MPS IIIA

experimental: Cohort B2

Participants with MPS IIIA

experimental: Cohort C1

Participants with MPS IIIA

Interventions

DNL126

intravenous repeating dose

Prophylactic immunomodulatory therapy

Per local prescribing information

Primary outcome measure

Part 1: Change from baseline in the natural logarithm of cerebrospinal fluid (CSF) heparan sulfate (HS) concentration [ Time Frame: 49 weeks ]

Central Contacts and Locations

Central contacts

Clinical Trials at Denali Therapeutics

Email clinical-trials@dnli.com

Locations

UCSF Benioff Children's Hospital Oakland

Recruiting

Oakland, California, United States, 94609

Contacts

Ivy Lee Hung

510-428-3885 Ivy.LeeHung@ucsf.edu

University of Iowa Stead Family Children's Hospital

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Lauren VanOpdorp

319-467-8197 lauren-vanopdorp@uiowa.edu

University of North Carolina at Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 27514

Contacts

Lindsay Torrice

919-966-1135 Lindsay_torrice@med.unc.edu

Baylor College of Medicine and Texas Children's Hospital

Recruiting

Houston, Texas, United States, 77030

Contacts

Varsha Yallamanchi

832-824-3323 varsha.yallamanchi@bcm.edu

Katherine Ann Asuncion

832-824-1421 KatherineAnn.Asuncion@bcm.edu

More Information

Sponsor

Denali Therapeutics Inc.

Last update posted

Nov 2, 2026

Last verified

Oct, 2026

Keywords

Sanfilippo Syndrome
MPS IIIA

Trial information was received from ClinicalTrials.gov and was last updated on 2026-11-03. This information was provided to ClinicalTrials.gov by Denali Therapeutics Inc. on 2026-11-02. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.