Long-Term Follow-Up Study for RB001 Gene Therapy Study in Children With SHANK3-related Phelan McDermid Syndrome (PMS)

RB001 is an adeno-associated virus (AAV) based gene therapy product. In the preceding RB001-101 clinical study (NCT07014020), 8 participants have been dosed. To date, no serious adverse events have been observed in any participant, and preliminary improvements were noted. In accordance with guidelines for gene therapy products and pediatric rare diseases, long-term follow-up is mandatory to monitor delayed adverse events, assess durability of efficacy, and evaluate long-term developmental benefits. Therefore, we designed this long-term follow-up (LTFU) study, which will roll over participants from the parent study to continuously track the long-term risks and benefits of RB001, providing critical long-term evidence for clinical application.

This is a long-term, safety and preliminary efficacy follow-up study of participants in the RB001-101 gene replacement therapy clinical trial for children with SHANK3-related Phelan-McDermid Syndrome (PMS), delivering RB001 via intracerebroventricular injection. Participants will roll over from the parent study into this long-term study for continuous safety and preliminary efficacy monitoring for a total of 5 years. The last visit of the parent study or early discontinuation from the parent study will serve as the visit at which the informed consent form process is conducted for this long-term follow-up study. Participants will return to the research center for follow-up visits every six months for 5 years (after RB001 administration). Additionally, patient record transfers from their local physician and/or neurologist will be requested in conjunction with these study visits for review by the investigator. If the patient is unable to return to the original investigative site, the sponsor will arrange with the patient's local established physician to serve as an additional investigator to conduct the required assessments.

• To evaluate the changes on Clinical Global Impression Scale - Severity (CGI-S) after a single intracerebroventricular injection of RB001 [Time frame: 1 to 5 years]
• To evaluate the changes on Clinical Global Impression Scale - Improvement (CGI-I) after a single intracerebroventricular injection of RB001 [Time frame: 1 to 5 years]
• To evaluate the changes on Patient's Global Impressions of Improvement (PGI-I) after a single intracerebroventricular injection of RB001 [Time frame: 1 to 5 years]
• To evaluate the changes on Childhood Autism Rating Scale (CARS-2) after a single intracerebroventricular injection of RB001 [Time frame: 1 to 5 years]
• To evaluate the changes on Autism Behavior Checklist (ABC) after a single intracerebroventricular injection of RB001 [Time frame: 1 to 5 years]
• To evaluate the changes on Griffith developmental assessment scale - Chinese (GDS-C) after a single intracerebroventricular injection of RB001 [Time frame: 1 to 5 years]
• To evaluate the changes on Peabody developmental motor scales - 2nd Edition (PDMS-2) after a single intracerebroventricular injection of RB001 [Time frame: 1 to 5 years]
• To evaluate the changes on Wechsler Preschool and Primary Scale of Intelligence (WPPSI) or Wechsler Intelligence Scale for Children (WISC) after a single intracerebroventricular injection of RB001 [Time frame: 1 to 5 years]
• To evaluate the changes on Adaptive Behavior Assessment System-Second Edition (ABAS-2) after a single intracerebroventricular injection of RB001 [Time frame: 1 to 5 years]
• To evaluate the changes on Social Life Ability Scale For Infant-Junior Middle School Student (S-M) after a single intracerebroventricular injection of RB001 [Time frame: 1 to 5 years]
• To evaluate the changes on Child Behavior Checklist (CBCL) after a single intracerebroventricular injection of RB001 [Time frame: 1 to 5 years]
• To evaluate the changes on Children's sleep habits questionnaire(CSHQ) after a single intracerebroventricular injection of RB001 [Time frame: 1 to 5 years]