Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)
a study on Mucopolysaccharidosis Sanfilippo Syndrome
Summary
- Eligibility
- for people ages 0-18 (full criteria)
- Location
- at UCSF
- Dates
- study startedcompletion around
- Principal Investigator
- by Paul Harmatz, MD (ucsf)
Description
Summary
This is a multicenter, open-label, Phase 1/2 study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and exploratory clinical efficacy of DNL126 in participants with Sanfilippo syndrome Type A (MPS IIIA). The core study period is 25 weeks (approximately 6 months) and is followed by a 72-week (approximately 18 month) open-label extension (OLE). Participants with MPS IIIA will be enrolled in two planned cohorts, and additional participants with MPS IIIA may be enrolled in three optional cohorts.
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)
Keywords
Mucopolysaccharidosis Type IIIA, Sanfilippo Syndrome, MPS IIIA, Mucopolysaccharidoses, Mucopolysaccharidosis III, DNL126
Eligibility
You can join if…
Open to people ages 0-18
- Confirmed diagnosis of MPS IIIA
- 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
You CAN'T join if...
- 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
Locations
- UCSF Benioff Children's Hospital Oakland
accepting new patients
Oakland California 94609 United States - Baylor College of Medicine and Texas Children's Hospita
accepting new patients
Houston Texas 77030 United States - University of Iowa Stead Family Children's Hospital
accepting new patients
Iowa City Iowa 52242 United States - University of North Carolina at Chapel Hill
accepting new patients
Chapel Hill North Carolina 27514 United States
Lead Scientist at University of California Health
- Paul Harmatz, MD (ucsf)
Details
- Status
- accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- Denali Therapeutics Inc.
- ID
- NCT06181136
- Phase
- Phase 1/2 research study
- Study Type
- Interventional
- Participants
- Expecting 20 study participants
- Last Updated