STXBP1-related encephalopathy
Conditions
Interventions
1. Dose climbing phase:Adeno-associated viral vector RF003 injection was injected into the lateral ventricle. Dose climbing stage: about 9-15 patients were used to explore the safe range of low, mediu
If DLT=2 cases, the climbing was stopped, and the previous dose was MTD (maximum tolerated dose). If >=2 DLTS occurred, enrollment at that dose was stopped immediately, and MTD was the previous dose l
2.Dose expansion cohort:Adeno-associated viral vector RF003 injection was injected into the lateral ventricle. Dose expansion cohort: approximately 15-21 patients for further evaluation of safety and
Sponsors
The Second Affiliated Hospital of Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
3 Years to 18 Years
Inclusion criteria
Inclusion criteria: 1.The informed consent process should comply with regulations, and the legal guardian of the subject voluntarily signs the informed consent form; 2.Age: 3 to 18 years old (inclusive of 3 years old); 3.Electroencephalogram and recorded clinical history are consistent with STXBP1 encephalopathy; 4.Genetic test results are consistent with the diagnosis of STXBP1 encephalopathy.
Exclusion criteria
Exclusion criteria: 1.If one exclusion criterion is met, the subject is excluded. 2.Organic diseases or medical histories that, in the judgment of the researcher, pose a risk to the safety of the subject, including diseases or histories of clinical significance in the cardiovascular, pulmonary, liver, kidney or reproductive systems, immune system, skeletal muscle system, nervous system (except STXBP1 encephalopathy), or other serious concurrent diseases; abnormal results of various laboratory tests before gene therapy, such as blood routine, blood biochemistry, urine routine, coagulation function, etc., which are clinically significant and judged by the researcher as not eligible for inclusion, or subjects who the researcher considers not suitable to participate in this trial (such as those with poor physical condition); 3.Unable to tolerate general anesthesia surgery; 4.Had fever or respiratory tract infection within two weeks before receiving the research product, or had vomiting or diarrhea within 24 hours before receiving the research product; 5.The subject or the guardian cannot comply with the regulations; 6.Had received gene therapy drugs within 6 months before receiving the research product; 7.The total antibody of AAV9 in blood or cerebrospinal fluid was detected by enzyme-linked immunosorbent assay (ELISA), and the total antibody titers of AAV9 in blood and cerebrospinal fluid were both = 1:50; 8.Planned to use antiviral drugs, immunoglobulin and interferon within 1 month after receiving the research product; 9.Unable to tolerate long-term use of prednisolone acetate.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence, severity, and relationship to the investigational drug of adverse events (AEs);Occurrence of Serious Adverse Events (SAE);Discontinuations or dose adjustments due to adverse events; | — |
Secondary
| Measure | Time frame |
|---|---|
| The effectiveness of intracerebroventricular injection of the adeno-associated virus vector RF003 injection solution in treating patients with STXBP1 encephalopathy;After intracerebral injection of the adeno-associated virus vector RF003 solution, the immune response of the body occurred;After intracerebral injection of the adeno-associated virus vector RF003 solution, the shedding of the virus in the body fluids was observed.; | — |
Countries
China
Contacts
Public ContactJianhua Feng
The Second Affiliated Hospital of Zhejiang University School of Medicine
Outcome results
None listed