A Natural History Study of Biomarkers and Clinical Outcomes in Mucopolysaccharidosis Type IIIA (MPS IIIA; Sanfilippo Syndrome)

Study Overview
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Brief Summary
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This protocol is a decentralized, single cohort, natural history and biomarker study enrolling up to 20 participants with MPS IIIA (Sanfilippo syndrome). At least 10 participants ( 50%) must be less than four years old at the time of the Parent/LAR consent. The study will have a screening process and 7 study visits, e.g. home visits, that will consist of serum collection and completion of a remote assessment of the Vineland Adaptive Behavior Scales 3rd Edition (Vineland-3) MPS IIIA remains a devastating disease with a high unmet medical need. There is currently a limited number of available data to adequately characterize the progression of the disease. Analysis of blood biospecimens and adaptive behavior in this study will help researchers better understand the clinical progression of MPS IIIA. A better understanding of disease progression may assist in developing novel therapies for rare genetic disorders.

Official Title
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A Natural History Study of Biomarkers and Clinical Outcomes in Mucopolysaccharidosis Type IIIA (MPS IIIA)

Conditions
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Mucopolysaccharidosis III-A

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of enrollment is as follows: All participants must be between 4 months and < 14 years at time of consent At least 10 participants (ie, approx. 50% of expected total population) must be between 4 months old and < 4 years old at the time of consent The participant has a confirmed diagnosis of Mucopolysaccharidosis Type IIIA (MPS IIIA) (i.e., Sanfilippo syndrome) based on at least 2 out of the 3 following criteria: Documented reduced N-sulphoglucosamine sulphohydrolase (SGSH) activity in plasma, white blood cells, and/or skin fibroblasts consistent with MPS IIIA (10% or less of the lower limit of the normal range based on the testing laboratory) Documented likely pathogenic variant of the SGSH gene Documented elevated heparan sulfate levels in urine and/or blood Participants and their families are willing to complete 7 blood draws and 7 Vineland-3 collections Exclusion Criteria: Known history of HIV, hepatitis, or other infectious diseases Taken an investigational product in the last 30 days Experienced excess blood loss, including blood donation, defined as 80 mL in the last month or 160 mL in the previous two months Undergone an MPS IIIA gene therapy at any time unless prior Sponsor or designee's approval has been received Documented loss of activity of sulfatases other than N-sulphoglucosamine sulphohydrolase (SGSH), indicating multiple sulfatase deficiency Known genetic or acquired disorder associated with developmental delay, seizures or other significant CNS dysfunction that would be expected to confound the clinical or biomarker assessments

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br>Participants with MPS IIIA | Other: No intervention<br>* No intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of adaptive behavior as measured by remote administration of the Vineland-3 Adaptive Behavior Scales (Vineland-3) |  | 96 weeks | 
| Change from baseline in levels of blood-based biomarkers in serum |  | 96 weeks |