ACTIVE_NOT_RECRUITING

Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)

Conditions

Mucopolysaccharidosis Type IIIA Sanfilippo Syndrome MPS IIIA

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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)

Quick Facts

Study Start:2023-12-07

Study Completion:2028-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06181136

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:0 Years to 18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Principal Investigator

Ana-Claire Meyer, MD

STUDY_DIRECTOR

Denali Therapeutics

Study Locations (Sites)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609

United States

University of Iowa Stead Family Children's Hospital

Iowa City, Iowa, 52242

United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514

United States

Baylor College of Medicine and Texas Children's Hospital

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Denali Therapeutics Inc.

Ana-Claire Meyer, MD, STUDY_DIRECTOR, Denali Therapeutics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-12-07

Study Completion Date2028-08

Study Record Updates

Study Start Date2023-12-07

Study Completion Date2028-08

Terms related to this study

Keywords Provided by Researchers

Sanfilippo Syndrome
MPS IIIA

Additional Relevant MeSH Terms

Mucopolysaccharidosis Type IIIA