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

A Long-term Follow-up Study of an Open-label, Single-arm, Single-dose Escalation Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Intracerebroventricular Injection of RB001 in Participants With SHANK3-related Phelan-McDermid Syndrome.

Status

Enrolling by invitation

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07690527

Acronym

RB001-101-LTFU

Enrollment

Registered

2026-07-08

Start date

2026-08-01

Completion date

2031-12-01

Last updated

2026-07-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Phelan-McDermid Syndrome, SHANK3 Haploinsufficiency

Keywords

AAV, SHANK3, Phelan-McDermid Syndrome, Gene therapy, 22q13.3 deletion syndrome

Brief summary

This is a long-term follow-up study of participants in the RB001-101 gene replacement therapy clinical trial for Children With SHANK3-related Phelan-McDermid Syndrome (PMS). Participants will roll over from the parent study into this long-term study for continuous safety monitoring and preliminary efficacy assessment for up to 5 years.

Detailed description

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.

Interventions

BIOLOGICALRB001

The study enrolled up to 2 cohorts, evaluating a higher or lower dose

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Single group assignment: an open-label, single arm, dose-escalation clinical study to evaluating the long-term safety, tolerability and preliminary efficacy of a single intracerebroventricular Injection of RB001

Eligibility

Sex/Gender

ALL

Healthy volunteers

Inclusion criteria

* Patients with SHANK3-related Phelan-McDermid Syndrome who have completed the last follow-up visit (Week 52 post-dosing) in the RB001-101 study.

Exclusion criteria

* Some conditions deemed unsuitable for participation in this study by the investigator

Design outcomes

Primary

Measure	Time frame	Description
To evaluate the safety and tolerability of a single intracerebroventricular injection of RB001	1 to 5 years	Types, severity, and incidence of adverse events (AEs) and serious adverse events (SAEs)

Secondary

Measure	Time frame	Description
To evaluate the changes on Clinical Global Impression Scale - Severity (CGI-S) after a single intracerebroventricular injection of RB001	1 to 5 years	Clinical Global Impression Scale (CGI) severity item provided with a seven-point scale of severity of patient's clinical condition (1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.)
To evaluate the changes on Clinical Global Impression Scale - Improvement (CGI-I) after a single intracerebroventricular injection of RB001	1 to 5 years	Clinical Global Impression Scale (CGI) Improvement item provided with a seven-point scale of improvement of patient's clinical condition (1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment.)
To evaluate the changes on Patient's Global Impressions of Improvement (PGI-I) after a single intracerebroventricular injection of RB001	1 to 5 years	The PGI-I consists of a single item in which participants or their parents rate the participant's overall health status relative to baseline using a 7 point scale, scale anchors correspond to those of the CGI-I: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse
To evaluate the changes on Childhood Autism Rating Scale (CARS-2) after a single intracerebroventricular injection of RB001	1 to 5 years	The CARS2 is a clinician completed rating scale based on direct observation of the child's behavior in standardized contexts. It comprises 15 descriptive items assessing domains including relating to people, imitation, emotional response, body use, object use, and adaptation to change. Each item is scored from 0 to 4, with 0 indicating no abnormality and 4 indicating severe abnormality. The rater integrates behavioral observations with an overall clinical impression of severity to compute a total score ranging from 15 to 60, and converted into a T-score through norm-referenced comparison. Higher T-scores indicate a higher level of autism severity, and a T-score \>40 indicates the presence of moderate or above autism related symptoms.
To evaluate the changes on Autism Behavior Checklist (ABC) after a single intracerebroventricular injection of RB001	1 to 5 years	The ABC is a clinician rated instrument based on direct observation of the child's behavior. It includes 57 items distributed across five domains: sensory, relating, body and object use, language, and self#help behavior. Each item is rated as either "yes" (present) or "no" (absent), based on whether the behavior is observed. The total score is calculated by summing the weighted scores of items endorsed as "yes" (item weights vary from 1 to 4). Higher total scores indicate greater autism#related behavioral impairment. The score is interpreted as follows: total \< 53 = negative (low risk), 53-67 = suspicious (moderate risk), and ≥ 68 = positive (high clinical concern for autism spectrum disorder).
To evaluate the changes on Griffith developmental assessment scale - Chinese (GDS-C) after a single intracerebroventricular injection of RB001	1 to 5 years	the Griffiths Developmental Assessment Scale - Chinese Version (GDS-C) is accessed by certified examiners. The scale evaluates 240 age-standardized tasks across six domains (Locomotor, Personal-Social, Language, Eye-Hand Coordination, Performance, and Practical Reasoning). Tasks are scored 0 or 1 (1=pass, 0=fail), with raw scores converted to Developmental Quotients (DQ) using China-specific norms (2020 revision). DQ\<85 suggests potential mild developmental delay, while a multi-domain DQ\<70 indicates significant developmental delay.
To evaluate the changes on Peabody developmental motor scales - 2nd Edition (PDMS-2) after a single intracerebroventricular injection of RB001	1 to 5 years	The PDMS-2 is a standardized, norm#referenced clinical tool used to assess gross and fine motor development in children. Certified clinicians administer age appropriate items across five domains: reflexes, stationary, locomotion, grasping, and object manipulation. each item is scored based on the child's level of performance, and raw scores are converted to standard scores, percentiles, and composite motor quotients including the gross motor quotient, fine motor quotient, and total motor quotient. Motor quotients are norm#referenced with a mean of 100 and standard deviation of 15. A motor quotient \< 85 indicates potential mild motor delay, while a quotient \< 70 suggests significant motor developmental impairment.
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	1 to 5 years	the certified neuropsychologist conducts assessments under standardized conditions and assigns scores based on five scales (Verbal Comprehension, Visual Spatial, Fluid/Quantitative Reasoning, Working Memory, Processing Speed) to derive a Full Scale IQ. Scores are norm-referenced (mean=100, SD=15), with higher values indicating superior cognitive ability. IQ\<85 suggests potential mild cognitive delay, while IQ\<70 indicates significant cognitive delay.
To evaluate the changes on Adaptive Behavior Assessment System-Second Edition (ABAS-2) after a single intracerebroventricular injection of RB001	1 to 5 years	To evaluate changes of functional adaptive behaviors from baseline at weeks 12, 26, and 52 after RB001 injection, the Adaptive Behavior Assessment System-Second Edition (ABAS-2) is administered. the rater (usually the Guardian) score the child's daily living skills across 10 domains (Communication, Self-Care, Social, etc.) using age-specific questionnaires. Items are scored 0-3 based on frequency of competent performance, and raw scores normalized to standard scores based on ages (mean=100, SD=15). The General Adaptive Composite (GAC) serves as the primary secondary endpoint. CAG \< 85 suggests potential mild delay, while CAG ≤ 70 indicates significant delay.
To evaluate the changes on Social Life Ability Scale For Infant-Junior Middle School Student (S-M) after a single intracerebroventricular injection of RB001	1 to 5 years	To evaluate adaptive functioning from baseline at weeks 12, 26, and 52 after RB001 injection, the Social Life Ability Scale for Infants-Junior Middle School Students (S-M Scale) is administered. Parents or primary caregivers observe the child's daily behaviors and score 132 specific items across six functional domains (Independent Living Skills, Motor Abilities, Practical Task Performance, Communication Skills, Self-Management, and Socialization). Each item is scored 0 or 1 (1 = pass, 0 = fail) based on observed capability. The total score (0-132) is calculated by summing all items, with higher scores indicating better adaptive functioning. A standard score ≤9 (equivalent to a raw score ≤70; ≥2 SD below the norm) suggests significant impairment in social adaptive abilities.
To evaluate the changes on Child Behavior Checklist (CBCL) after a single intracerebroventricular injection of RB001	1 to 5 years	To evaluate behavioral/emotional problems from baseline at weeks 12, 26, and 52 after RB001 injection, the Child Behavior Checklist (CBCL) is administered. Parents or caregivers rate the child's behaviors using 113+ problem items across empirically based syndromes (Anxious/Depressed, Withdrawn/Depressed, Somatic Complaints, Social Problems, Thought Problems, Attention Problems, Rule-Breaking Behavior, and Aggressive Behavior). Each item is scored 0-2 (0 = not true, 1 = sometimes true, 2 = very/often true). The total problem score (0-240) is calculated by summing all items, with higher scores indicating greater behavioral/emotional impairment. A T-score \>63 (\>90th percentile) suggests clinical concern, and \>70 (\>98th percentile) indicates. (T-scores (M = 50, SD = 10) are derived from normative samples).
To evaluate the changes on Children's sleep habits questionnaire(CSHQ) after a single intracerebroventricular injection of RB001	1 to 5 years	The CSHQ is a validated parent report screening tool used to assess sleep patterns and common sleep disturbances in children. Parents or primary caregivers rate their child's recent sleep behaviors across multiple domains, including bedtime resistance, sleep onset latency, sleep duration, night wakings, sleep anxiety, parasomnias, sleep disordered breathing, and daytime sleepiness. The questionnaire consists of 45 items, each scored on a frequency scale based on how often the behavior occurred during the past week: 1 = frequently (5-7 times), 2 = sometimes (2-4 times), and 3 = rarely (0-1 times). The total score is computed using the established scoring criteria; higher score indicate more severe sleep problems.
To evaluate AAV neutralizing antibodies after a single intracerebroventricular injection of RB001	1 to 5 years	To evaluate AAV neutralizing antibodies (Abs) titer after RB001 injection. blood samples will be collected at each time point. Antibodies will be quantified using cell-coculture method.

Countries

China

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Jul 14, 2026