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

Mucopolysaccharidosis Type IIIA Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06181136
• Other study ID #: DNLI-I-0001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 7, 2023
• Est. completion date: August 2028

Study information

• Verified date: April 2024
• Source: Denali Therapeutics Inc.
• Contact: Clinical Trials at Denali Therapeutics
• Phone: Email
• Email: clinical-trials[@]dnli.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 8
• Est. completion date: August 2028
• Est. primary completion date: August 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

Key Inclusion Criteria:

• Confirmed diagnosis of MPS IIIA

Key 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

• 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 within 30 days of screening or intended use of genistein 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

Related Conditions & MeSH terms

• Mucopolysaccharidoses
• Mucopolysaccharidosis III
• Mucopolysaccharidosis Type IIIA

Intervention

Drug:
• DNL126
intravenous repeating dose

Locations

Country	Name	City	State
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Baylor College of Medicine and Texas Children's Hospita	Houston	Texas
United States	University of Iowa Stead Family Children's Hospital	Iowa City	Iowa
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California

Sponsors (1)

Lead Sponsor	Collaborator
Denali Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs)		Up to 97 weeks
Primary	Number of participants with clinically significant treatment emergent laboratory test abnormalities.		Up to 97 weeks
Primary	Number of participants with treatment emergent vital sign abnormalities.		Up to 97 weeks
Primary	Number of participants with clinically significant treatment emergent abnormalities in 12-lead ECG results.		Up to 97 weeks
Primary	Number of participants with clinically significant treatment emergent abnormalities in physical examination.		Up to 97 weeks
Primary	Number of participants with clinically significant treatment emergent abnormalities in neurological examination.		Up to 97 weeks
Primary	Incidence and severity of infusion-related reactions (IRRs)		Up to 97 weeks
Secondary	Percentage change from baseline in cerebrospinal fluid (CSF) concentration of heparan sulfate (HS)		Up to 97 weeks
Secondary	Participants with CSF HS concentration within the normal range		Up to 97 weeks
Secondary	Percentage change from baseline in urine concentration of HS (normalized to creatinine)		Up to 97 weeks
Secondary	Participants with urine HS concentration (normalized to creatinine) within the normal range		Up to 97 weeks
Secondary	Participants with liver volume within the normal range		Up to 97 weeks
Secondary	Change from baseline in liver volume		Up to 97 weeks
Secondary	Participants with spleen volume within the normal range		Up to 97 weeks
Secondary	Change from baseline in spleen volume		Up to 97 weeks
Secondary	Maximum concentration (Cmax)	DNL126 serum PK parameters	Up to 97 weeks
Secondary	time to maximum observed concentration (Tmax)	DNL126 serum PK parameters	Up to 97 weeks
Secondary	area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast)	DNL126 serum PK parameters	Up to 97 weeks
Secondary	area under the concentration-time curve from time zero to infinity (AUC8; single dose only)	DNL126 serum PK parameters	Up to 97 weeks
Secondary	DNL126 serum PK parameters	area under the concentration-time curve over a dosing interval (AUCt; multiple doses only)	Up to 97 weeks
Secondary	apparent terminal elimination half-life (t½)	DNL126 serum PK parameters	Up to 97 weeks
Secondary	Incidence of anti-drug antibodies (ADAs) relative to baseline		Up to 97 weeks