RB001 gene therapy for children with SHANK3-related Phelan-McDermid syndrome
An Open-label, Single Arm, Dose-Escalation Clinical Study to Evaluating the Safety, Tolerability and Preliminary Efficacy of a Single Intracerebroventricular Injection of RB001 for the Treatment of SHANK3-related Phelan McDermid Syndrome.
This trial will test whether a single RB001 gene therapy injection into the brain is safe and can help children aged 3 to 17 with SHANK3-related Phelan-McDermid syndrome.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 8 (estimated) |
| Ages | 3 Years to 18 Years |
| Sex | All |
| Sponsor | Peking University First Hospital Academic / other |
| Drugs / interventions | rituximab, methotrexate, cyclophosphamide, prednisone |
| Locations | 1 site (Beijing, Beijing Municipality) |
| Trial ID | NCT07014020 on ClinicalTrials.gov |
What this trial studies
This first-in-human, open-label, dose-escalation trial delivers an AAV vector carrying an optimized SHANK3-minigene by intracerebroventricular (ICV) injection to pediatric participants with genetically confirmed SHANK3-related Phelan-McDermid syndrome. Up to eight children aged 3 to under 18 will receive a single surgical ICV administration and be monitored for safety, tolerability, biomarker changes, and preliminary clinical activity. Clinical assessments, biological samples, and follow-up visits will be used to track adverse events and signals of benefit over time. The intervention is supported by animal data showing restored SHANK3 expression and improved behavior in SHANK3-mutant models, but human efficacy is unproven.
Who should consider this trial
Good fit: Ideal candidates are children aged 3 to under 18 with genetically and clinically confirmed SHANK3-related Phelan-McDermid syndrome, moderate-or-greater ASD, IQ or developmental quotient below 70, and caregivers willing to consent and accept hospital admission for ICV surgery and follow-up.
Not a fit: Patients without SHANK3-related PMS, those with only mild symptoms, prior participation in AAV or PMS drug trials, or those with contraindications to neurosurgery or severe comorbidities are unlikely to benefit from this study.
Why it matters
Potential benefit: If successful, RB001 could restore SHANK3 expression in the brain and improve developmental, language, or behavioral symptoms in affected children.
How similar studies have performed: This is the first reported human trial targeting SHANK3 replacement; animal studies showed benefit, and AAV gene therapies for other neurogenetic disorders have demonstrated clinical success, but human data for SHANK3 are not yet available.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Exclusion Criteria: 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
Where this trial is running
Beijing, Beijing Municipality
- Peking University First Hospital — Beijing, Beijing Municipality, China (Recruiting)
Study contacts
- Study coordinator: Dongliang Li
- Email: 17639843553@163.com
- Phone: 17639843553
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.