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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
intravenous repeating dose
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States
University of Iowa Stead Family Children's Hospital
Iowa City, Iowa, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Baylor College of Medicine and Texas Children's Hospital
Houston, Texas, United States
Percentage change from baseline in cerebrospinal fluid (CSF) concentration of heparan sulfate (HS)
Time frame: 49 weeks
Percentage change from baseline in urine concentration of HS (normalized to creatinine)
Time frame: 49 weeks
Change from baseline in liver volume
Time frame: 49 weeks
Percentage change from baseline in serum neurofilament light chain (NfL) concentration
Time frame: 73 weeks
Participants with CSF HS concentration within the normal range
Time frame: 49 weeks
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