Status:
ACTIVE_NOT_RECRUITING
Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)
Lead Sponsor:
Denali Therapeutics Inc.
Conditions:
Mucopolysaccharidosis Type IIIA
Eligibility:
All Genders
Up to 18 years
Phase:
PHASE1
PHASE2
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 synd...
Eligibility Criteria
Inclusion
- Key
- 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
- 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
Key Trial Info
Start Date :
December 7 2023
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 1 2028
Estimated Enrollment :
20 Patients enrolled
Trial Details
Trial ID
NCT06181136
Start Date
December 7 2023
End Date
August 1 2028
Last Update
December 5 2025
Active Locations (4)
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1
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States, 94609
2
University of Iowa Stead Family Children's Hospital
Iowa City, Iowa, United States, 52242
3
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27514
4
Baylor College of Medicine and Texas Children's Hospital
Houston, Texas, United States, 77030