Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)
- Conditions
- Mucopolysaccharidosis Type IIIA
- Registration Number
- NCT06181136
- Lead Sponsor
- Denali Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 20
Key Inclusion Criteria:<br><br> - Confirmed diagnosis of MPS IIIA<br><br> - For Cohort B1: Have a severe phenotype based on having at least one of the<br> following:<br><br> - An older sibling with the same genotype and severe MPS IIIA, in the opinion of<br> the investigator<br><br> - A definitive genotype indicative of severe MPS IIIA, in the opinion of the<br> investigator<br><br> - Clinical symptoms of MPS IIIA prior to 28 months of age that, in the opinion of<br> the investigator, are indicative of severe MPS IIIA<br><br> - For Cohort B2: Are an older sibling of a participant in Cohort B1 (who has already<br> been confirmed to be eligible for dosing) with MPS IIIA, the same causative<br> genotype, and who has severe MPS IIIA in the opinion of the investigator<br><br>Key Exclusion Criteria:<br><br> - Have unstable or poorly controlled medical condition(s) or significant medical or<br> psychological comorbidity or comorbidities that, in the opinion of the investigator,<br> would interfere with safe participation in the trial or interpretation of study<br> assessments<br><br> - Have lost the ability to walk independently, in the opinion of the investigator<br><br> - Are unable to take the majority of nutrition via mouth, in the opinion of the<br> investigator<br><br> - For Cohort B only: Are homozygous or compound heterozygous for the<br> N-sulfoglucosamine sulfohydrolase (SGSH) S298P mutation or any other mutation known<br> to be associated with slow-progressing phenotype<br><br> - Have used any CNS-targeted MPS IIIA enzyme replacement therapy (ERT) (eg,<br> intrathecal SGSH or TfR-mediated SGSH delivery to CNS) within 3 months before Day 1<br><br> - Have a prior history of hematopoietic stem cell transplantation<br><br> - Have a prior history of gene therapy<br><br> - Have used genistein or anakinra within 7 days of screening or intended use of<br> genistein or anakinra during the study<br><br> - Have a documented likely pathogenic mutation sufficient to cause disease (eg, taking<br> into account zygosity) of other genes that are known to be associated with<br> developmental delay, seizures, or other significant CNS disorders<br><br> - Have clinically significant thrombocytopenia, other clinically significant<br> coagulation abnormality, significant active bleeding, or require treatment with an<br> anticoagulant or more than two antiplatelet agents<br><br> - Contraindication for lumbar punctures<br><br> - Contraindication for MRI scan<br><br> - Have a clinically significant history of stroke, status epilepticus, head trauma<br> with loss of consciousness, or any clinically significant CNS disease that is not<br> MPS IIIA-related within 3 months of screening<br><br> - Have had a ventriculoperitoneal (VP) shunt placed or a clinically significant VP<br> shunt malfunction within 30 days of screening<br><br> - Have any clinically significant CNS trauma or disorder, including severe untreated<br> intracranial hypertension or brain surgery, that, in the opinion of the<br> investigator, may interfere with assessment of study endpoints or make participation<br> in the study unsafe
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs);Number of participants with clinically significant treatment emergent laboratory test abnormalities.;Number of participants with treatment emergent vital sign abnormalities.;Number of participants with clinically significant treatment emergent abnormalities in 12-lead ECG results.;Number of participants with clinically significant treatment emergent abnormalities in physical examination.;Number of participants with clinically significant treatment emergent abnormalities in neurological examination.;Incidence and severity of infusion-related reactions (IRRs)
- Secondary Outcome Measures
Name Time Method Percentage change from baseline in cerebrospinal fluid (CSF) concentration of heparan sulfate (HS);Participants with CSF HS concentration within the normal range;Percentage change from baseline in urine concentration of HS (normalized to creatinine);Participants with urine HS concentration (normalized to creatinine) within the normal range;Participants with liver volume within the normal range;Change from baseline in liver volume;Participants with spleen volume within the normal range;Change from baseline in spleen volume;Maximum concentration (Cmax);time to maximum observed concentration (Tmax);area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast);area under the concentration-time curve from time zero to infinity (AUC8; single dose only);DNL126 serum PK parameters;apparent terminal elimination half-life (t½);Incidence of anti-drug antibodies (ADAs) relative to baseline