SHANK3-related Phelan-McDermid syndrome
Conditions
Interventions
Cohort 1:Intracerebroventricular Injection of RB001, drug titer: 4 x 10^13vg/mL, delivery volume: 5mL, dose: 2x10^14vg/person
Cohort 2:Intracerebroventricular Injection of RB001, drug titer: 4 x 10^13vg/mL, delivery volume: 10mL, dose: 4x10^14vg/person
Sponsors
Peking University First Hospital
Eligibility
Sex/Gender
All
Age
3 Years to 18 Years
Inclusion criteria
Inclusion criteria: 1) Age >=3 years and <18 years (at the time of signing informed consent), any gender; 2) Genetic test and clinical confirmed diagnosis of SHANK3-related PMS; 3) Meets diagnostic criteria for moderate or more severe Autism Spectrum Disorder (ASD); 4) Intelligence Quotient (IQ) score <70 or Developmental Quotient (DQ) (excluding gross motor) average score <70; 5) Willing to provide biological samples required for the study (e.g., blood, urine); 6) Consent to hospitalization for intracerebroventricular injection surgery; 7) 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
Exclusion criteria: A pediatric participant who meets any of the following criteria will be excluded from this study: 1) Previous or current participation in other PMS drug clinical trials or other AAV gene therapy clinical studies; 2) Has known allergic constitution, including allergy or hypersensitivity to prednisone acetate, other glucocorticosteroids, their excipients, or local anesthetics; 3) Subjects with status epilepticus within 3 months prior to enrollment; 4) Subjects requiring invasive or non-invasive ventilatory support; 5) Serum anti-AAV neutralizing antibody titer >1:200; 6) Significant laboratory abnormalities: alanine aminotransferase (ALT), aspartate aminotransferase (AST), ?-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; 7) Subjects with liver disease or history of heart disease that may pose drug-related risks as assessed by the investigator; 8) Subjects deemed unsuitable for intracerebroventricular administration or with other special circumstances as assessed by the investigator; 9) 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; 10) 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); 11) Other conditions deemed unsuitable for participation in this study by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluation of the safety and tolerability of different dose levels of RB001 after a single lateral ventricular administration up to week 52; | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation of preliminary efficacy of different dose levels of RB001 after single lateral ventricular administration through 52 weeks in subjects with SHANK3-associated PMS;Evaluation of Adeno-associated disease (AAV) viral load in SHANK3-associated PMS subjects after single lateral ventricular administration of RB001 at different dose levels up to week 52;Evaluation of adeno-associated virus (AAV) viral shedding in SHANK3-associated PMS subjects after single lateral ventricular administration of RB001 at different dose levels up to week 52;Evaluation of immunogenic saliva, urine, and fecal tests in SHANK3-associated PMS subjects after a single lateral ventricular administration of RB001 at different dose levels through week 52; | — |
Countries
China
Contacts
Public ContactYe Wu
Peking University First Hospital
Outcome results
None listed