Natural History to Assess Disease in Patients With MPS IIIC

Observational Study to Assess Disease Symptoms and Progression in Participants With Sanfilippo Syndrome Type C (Mucopolysaccharidosis Type III [MPS III] C)

This is a REMOTE prospective observational study of participants with MPS IIIC.

No investigational medicinal product will be administered as part of this study.

Patients functional abilities will be captured using video recordings taken by patients legal representative or caregiver using a dedicated clinical video application downloaded from the internet onto a smartphone. The video application is called C-RARE.

Electronic observer-reported outcome (ObsRO) questionnaires will be completed by the legal representatives or caregivers via C-RARE.

The study will last two years with videos and questionnaires taken every 6 months for a total of 5 time points. Data will then be reviewed and measured for functional change using a scoring scale designed for the use of this study.

The study will be conducted remotely; no in-person visits are required. Approximately 35 participants with MPS IIIC will be enrolled in the study through a study site in the United States of America (USA). Enrollment of the first 25 participants with age ≤10 years will help ensure that the data collected from these younger participants will provide a better understanding of the early phase of the disease that may be relevant for future drug development. The remaining 10 participants will be between 11 to 25 years of age. The cutoff for the study is 25 years old. Participants speaking either Spanish, Portuguese, German, French or English may enroll in the study.

At Screening (Visit 1), the site coordinator based at UT Southwestern will review the laboratory report with a confirmed diagnosis of Hgsnat-deficiency MPS IIIC and a mutational analysis report demonstrating homozygous or compound heterozygous, pathogenic, and/or potentially pathogenic variants in the Hgsnat gene to assess the eligibility of the participants. After confirming diagnosis by the site coordinator, the caregiver or legal representative(s) will read and sign the informed consent form electronically, and when possible, the participant will provide adult or pediatric assent electronically.

At Baseline (Visit 2), the legal representative(s) or caregiver will be asked to complete electronic demographics and medical record questionnaire via the C-RARE App.

At Baseline (Visit 2) and at 6-month intervals (from Visit 3 through the end of the study), the legal representative(s) or caregiver will be asked to complete questionnaires and record home video assessments using a dedicated study app called C-RARE. Functional and cognitive abilities will be captured in the home environment by video and PEDI-CAT, an electronic a caregiver reported outcome assessment.

The legal representative(s) or caregiver will be provided with a C-RARE kit (via mailing), which includes a manual and props, as well as training for using the app. Baseline at-home visit (demographics, medical/surgical history, concomitant medications/therapy history, video and PEDI-CAT assessment, and ObsRO) should be completed at Visit 2. At-home Visit 3 to Visit 6 (video, PEDI-CAT assessment, and ObsRO) should be completed within a 14-day period for each visit. The legal representative(s) or caregiver will be provided with the timeline for each visit.

The study population will include participants with a confirmed diagnosis of MPS IIIC. Participants will be recruited for approximately 3 months by patient organizations. The patient organizations will provide participants with details of the site coordinator at UTSW. Participant-level data will be obtained through C-RARE app and PEDI-CAT.

Inclusion Criteria:

• 1. ≥1 year and ≤ 25 years of age 2. Confirmed diagnosis of MPS IIIC by all of the following:

  1. Deficiency in the Hgsnat enzyme activity

  2. Genetic analysis demonstrating homozygous or compound heterozygous, pathogenic, and/or potentially pathogenic variants in the Hgsnat gene

  3. Signs/symptoms consistent with MPS IIIC, or individuals who have not presented with signs/symptoms of disease but meet inclusion criteria 2a and 2b 3. Electronic informed consent from legal representative(s) or caregivers and when possible, pediatric or adult assent from the participant 4. One of the legal representative(s) or the caregivers is willing to perform at home visits and assessments per instruction 5. Ability to comply with protocol requirements, in the opinion of the Investigator 6. Able to take food or liquid by mouth, able to walk with or without assistance 7. Participants must have health insurance 8. Caregiver willing and able to comply with protocol requirements, including performing at-home visits and assessments 9. Participants must have smart phone or tablet and reliable internet connection 10. Have one of these languages as their first language: English, Spanish, French, German or Portuguese

     Exclusion Criteria:

     1. Have received prior gene therapy or ERT for the treatment of MPS IIIC ever or any other investigational drug for any reason within 30 days prior to the Screening visit (Visit 1)
     2. Have concomitant illness or medical condition that, in the opinion of the Investigator, might compromise the participant's ability to comply with protocol requirements or the participant's wellbeing or safety, or the interpretability of the participant's clinical data