RB001 Gene Therapy Study in Children With SHANK3-related Phelan McDermid Syndrome (PMS)

NCT07014020 | Recruiting

• 2 other identifiers: RB001-1012025R0116-0002
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first in human, open-label, dose-escalation study to evaluate the safety, tolerability, and clinical activity of a single dose of RB001 administered via intracerebroventricular (ICV) injection in pediatric with SHANK3 related Phelan-McDermid Syndrome. Clinical data will be evaluated for safety, tolerability, and preliminary efficacy of RB001 in participants with SHANK3 related PMS.

Conditions

Phelan-McDermid Syndrome; SHANK3 Haploinsufficiency

Keywords

AAV; SHANK3; Phelan-Mecdermid Syndrome; 22q13.3 deletion syndrome

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of a single intracerebroventricular injection of RB001 through week 52

  Types, severity, and incidence of adverse events (AEs) and serious adverse events (SAEs) within 52 weeks after RB001 injection

  52 weeks

Secondary Outcomes (15)

• To evaluate the changes on Clinical Global Impression Scale - Severity (CGI-S) after a single intracerebroventricular injection of RB001 through week 52

  52 weeks

• To evaluate the changes on Clinical Global Impression Scale - Improvement (CGI-I) after a single intracerebroventricular injection of RB001 through week 52

  52 weeks

• To evaluate the changes on Patient's Global Impressions of Improvement (PGI-I) after a single intracerebroventricular injection of RB001 through week 52

  52 weeks

• To evaluate the changes on Childhood Autism Rating Scale (CARS-2) after a single intracerebroventricular injection of RB001 through week 52

  52 weeks

• To evaluate the changes on Autism Behavior Checklist (ABC) after a single intracerebroventricular injection of RB001 through week 52

  52 weeks

Other Outcomes (5)

• To evaluate changes in sleep patterns after a single intracerebroventricular injection of RB001 through week 52

  52 weeks

• To evaluate changes in facial processing and emotional perception abilities after a single intracerebroventricular injection of RB001 through week 52

  52 weeks

• To evaluate the changes in olfactory performances after a single intracerebroventricular injection of RB001 through week 52

  52 weeks

Study Arms (1)

RB001

EXPERIMENTAL

Once intracerebroventricular injection; The duration of the study is about 14 months for each subject, including a 2-month screening period, an inpatient period from Day 1 (Dosing) to Day 7 post-administration and a subsequent 12-month outpatient follow-up period.

Genetic: RB001

Interventions

RB001 GENETIC

The study will enroll up to 2 cohorts, evaluating a starting dose plus a higher or lower dose

RB001

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age ≥3 years and \<18 years (at the time of signing informed consent), any gender
• Genetic test and clinical confirmed diagnosis of SHANK3-related PMS
• Meets diagnostic criteria for moderate or more severe Autism Spectrum Disorder (ASD)
• Intelligence Quotient (IQ) score \<70 or Developmental Quotient (DQ) (excluding gross motor) average score \<70
• Willing to provide biological samples required for the study (e.g., blood, urine)
• Consent to hospitalization for intracerebroventricular injection surgery
• The holders of parental authority who are able to understand and willing to comply with study requirements and procedures, voluntarily participating and signing the informed consent

You may not qualify if:

• A pediatric participant who meets any of the following criteria will be excluded from this study:
• Previous or current participation in other PMS drug clinical trials or other AAV gene therapy clinical studies
• Has known allergic constitution, including allergy or hypersensitivity to prednisone acetate, other glucocorticosteroids, their excipients, or local anesthetics
• Subjects with status epilepticus within 3 months prior to enrollment
• Subjects requiring invasive or non-invasive ventilatory support
• Serum anti-AAV neutralizing antibody titer \>1:200
• Significant laboratory abnormalities: alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT) with any value above the upper limit of normal; total bilirubin above the upper limit of normal; creatinine ≥159 μmol/L; hemoglobin (Hb) \<80 g/L; prothrombin time (PT) prolonged by ≥3 seconds; activated partial thromboplastin time (APTT) prolonged by ≥10 seconds; fasting blood glucose ≥7.0 mmol/L; glycated hemoglobin (HbA1c) ≥6.5%; platelets (PLT) \<100×10\^9/L
• Subjects with liver disease or history of heart disease that may pose drug-related risks as assessed by the investigator
• Subjects deemed unsuitable for intracerebroventricular administration or with other special circumstances as assessed by the investigator
• Positive for human immunodeficiency virus antibody, hepatitis B surface antigen, hepatitis C antibody, syphilis antibody, active TORCH virus infection, or active Epstein-Barr virus infection
• Concomitant use of any of the following medications within 90 days prior to administration, or planned immunosuppressive treatment within 3 months after starting the trial, except for prophylactic medications specified in the protocol (cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab, etc. )
• Other conditions deemed unsuitable for participation in this study by the investigator

Sponsors & Collaborators

• Peking University First Hospital: lead
• Shenzhen Reborngene Therapeutics Co., Ltd.: collaborator
• Shenzhen Institutes of Advanced Technology ,Chinese Academy of Sciences: collaborator

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Conditions

Telomeric 22q13 Monosomy Syndrome

Central Study Contacts

Dongliang Li

CONTACT

17639843553; 17639843553@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Physician

Model Details: An Open-label, Single Arm, Dose-Escalation Clinical Study to Evaluating the Safety, Tolerability and Preliminary Efficacy of a Single Intracerebroventricular Injection of RB001

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: June 10, 2025
• Study Start: June 16, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 30, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)