Treatment for children with Sanfilippo Syndrome Type A using DNL126
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 study is testing a new treatment called DNL126 to see if it can help children with Sanfilippo Syndrome Type A feel better and improve their condition.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 26 (estimated) |
| Ages | 0 Years to 18 Years |
| Sex | All |
| Sponsor | Denali Therapeutics Inc. Industry-sponsored |
| Locations | 4 sites (Oakland, California and 3 other locations) |
| Trial ID | NCT06181136 on ClinicalTrials.gov |
What this trial studies
This multicenter, open-label Phase 1/2 study evaluates the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical efficacy of DNL126 in pediatric participants diagnosed with Mucopolysaccharidosis Type IIIA, also known as Sanfilippo Syndrome Type A. The study consists of a core period lasting 25 weeks, followed by an open-label extension lasting 72 weeks. Participants will be enrolled in two main cohorts, with the possibility of additional participants in three optional cohorts based on specific eligibility criteria related to the severity of their condition.
Who should consider this trial
Good fit: Ideal candidates for this study are pediatric patients with a confirmed diagnosis of Mucopolysaccharidosis Type IIIA, particularly those exhibiting severe phenotypes.
Not a fit: Patients with unstable or poorly controlled medical conditions may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could significantly improve the clinical outcomes and quality of life for children suffering from Sanfilippo Syndrome Type A.
How similar studies have performed: Other studies targeting similar conditions have shown promise, but this specific approach with DNL126 is novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Key Inclusion Criteria: * Confirmed diagnosis of MPS IIIA * For Cohort A2: 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 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
Where this trial is running
Oakland, California and 3 other locations
- UCSF Benioff Children's Hospital Oakland — Oakland, California, United States (Recruiting)
- University of Iowa Stead Family Children's Hospital — Iowa City, Iowa, United States (Recruiting)
- University of North Carolina at Chapel Hill — Chapel Hill, North Carolina, United States (Recruiting)
- Baylor College of Medicine and Texas Children's Hospita — Houston, Texas, United States (Recruiting)
Study contacts
- Study coordinator: Clinical Trials at Denali Therapeutics
- Email: clinical-trials@dnli.com
- Phone: Email
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.