Natural History Study of Participants With Sanfilippo Syndrome Type IIIC

A Combination Retrospective and Prospective Natural History Study of Participants With Sanfilippo Syndrome Mucopolysaccharidosis Type IIIC (MPS IIIC)

This study is planned to document, through retrospective and prospective data collection, syndrome progression in children and young adults with MPS IIIC.

This is a multi-center, natural history study of subjects with Sanfilippo syndrome type C or MPS IIIC. This study will combine a retrospective review of medical records and an ongoing collection of clinical data on an observational basis. Real-world data will be collected at home using a recording device.

Participants will be asked to attend clinic visits in person on a yearly basis. In clinic visits will include neurocognitive, developmental, behavioral, biochemical, imaging measures as well as retrospective medical record analysis.

At 6-month intervals between clinic visits, participants will be contacted remotely for some safety assessments (e.g., collecting information about concomitant medications, concurrent illnesses, and procedure-related adverse events [AEs] and serious AEs [SAEs] since last clinic visit).

At 6-month intervals, caregivers will complete questionnaires and record home video assessments using a dedicated, compliant study application (app) called C-RARE (Recording Application for Real-World Evidence). The C-RARE app consists of 9 tasks of Activities of Daily Living and socialization as well as three parent reported Sanfilippo specific questionnaires.

The objectives of this study are:

• To enhance the understanding of the natural history and progression of MPS IIIC syndrome on behavior, cognitive abilities, mobility, vision, hearing, speech, and expressive and receptive language
• To define and categorize clinical endpoints that may be used in future clinical trials

Inclusion Criteria:

Confirmed diagnosis of Sanfilippo syndrome type C disease by all of the following:

• Deficiency in heparan-alpha-glucosaminide N-acetyltransferase enzyme activity
• Has presented with signs/symptoms consistent with Sanfilippo syndrome type C, or, for individuals who have not presented with signs/symptoms of disease (eg, siblings of known patients), the determination of eligibility will be at the discretion of the Sponsor in conjunction with the site Investigator
• Genomic DNA analysis demonstrating homozygous or compound heterozygous, pathogenic and/or potentially pathogenic variants in the HGSNAT gene
• Accumulated GAG HS in urine
• Written informed consent from parent or legal guardian and assent from patient, if required
• Parent/legal guardian willing to accompany the patient to all study visits
• Ability to comply with protocol requirements, in the opinion of the Investigator
• Negative urine pregnancy test at screening (nonsterile females of childbearing potential only).

Functional abilities:

• Able to take food or liquid by mouth, able to walk with or without assistance.
• Has an age equivalent on the Vineland Adaptive Behavior Scales (VABS) of ≥1 year.

Exclusion Criteria:

Patients who meet any of the following criteria will not be eligible to participate in the study:

• Have received an investigational drug within 30 days prior to the Baseline Visit
• Concomitant illness or medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the patient's ability to comply with protocol requirements, the patient's well-being or safety, or the interpretability of the patient's clinical data
• The presence of significant non-MPS IIIC-related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study