Clinical Trials/NCT06181136

NCT06181136

Active, not recruiting

Phase 1

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)

Denali Therapeutics Inc.4 sites in 1 country20 target enrollmentDecember 7, 2023

ConditionsMucopolysaccharidosis Type IIIA

InterventionsDNL126

DrugsDNL126

Overview

Phase: Phase 1
Intervention: DNL126
Conditions: Mucopolysaccharidosis Type IIIA
Sponsor: Denali Therapeutics Inc.
Enrollment: 20
Locations: 4
Primary Endpoint: Percentage change from baseline in cerebrospinal fluid (CSF) concentration of heparan sulfate (HS)
Status: Active, not recruiting
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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). 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 193 (Year 4). Participants with MPS IIIA will be enrolled in two planned cohorts, and additional participants with MPS IIIA may be enrolled in three optional cohorts.

Registry

clinicaltrials.gov

Start Date

December 7, 2023

End Date

August 1, 2028

Last Updated

4 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Denali Therapeutics Inc.

Responsible Party

Sponsor

Eligibility Criteria

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

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

Arms & Interventions

Cohort A1

Participants with MPS IIIA

Intervention: DNL126

Cohort A2

Participants with MPS IIIA

Intervention: DNL126

Cohort A3

Participants with MPS IIIA

Intervention: DNL126

Cohort B1

Participants with MPS IIIA

Intervention: DNL126

Cohort B2

Participants with MPS IIIA

Intervention: DNL126

Outcomes

Primary Outcomes

Percentage change from baseline in cerebrospinal fluid (CSF) concentration of heparan sulfate (HS)

Time Frame: 49 weeks

Secondary Outcomes

Percentage change from baseline in urine concentration of HS (normalized to creatinine)(49 weeks)
Change from baseline in liver volume(49 weeks)
Percentage change from baseline in serum neurofilament light chain (NfL) concentration(73 weeks)
Participants with CSF HS concentration within the normal range(49 weeks)