Single-Dose AAV-MECP2 Safety/Tolerability and Efficacy in Rett Syndrome

Launched by GUANGZHOU WOMEN AND CHILDREN'S MEDICAL CENTER · Feb 26, 2025

Keywords

ClinConnect Summary

This clinical trial is investigating a new gene therapy called AAV-MECP2 for treating Rett Syndrome, a severe condition that affects girls and leads to social and developmental challenges. The study aims to understand how safe and effective a single injection of this therapy is in girls aged 4 to 10 who have been diagnosed with Rett Syndrome due to specific genetic mutations. The researchers will test two different doses of the therapy and will include three participants for each dose to see how well they tolerate it and whether it helps improve their symptoms.

To be eligible for the trial, participants must be female, between 4 and 10 years old, and have a confirmed diagnosis of Rett Syndrome with a specific gene mutation. They also need to have completed all required vaccinations before joining the study. Participants and their guardians will need to consent to the procedures involved, which include a spinal injection and providing some biological samples for testing. It’s important to note that girls with certain other health issues or conditions may not be able to participate. If you think your child might be eligible and are interested in learning more, please talk to your doctor for further information.

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • 1. 4-10 years old (at the time of signing the informed consent form), female, who meets the typical RTT diagnosis criteria in 2010.
• • 2. Gene testing confirms functional loss mutations in the MECP2 gene.
• • 3. Complete all Class I vaccination required by the national regulations before the age of enrollment, and the final dose of vaccination must be completed at least 42 days before enrollment.
• • 4. Participate in this study with the informed consent of the guardian, understand the risks of intrathecal injection procedures, and agree to collect blood, urine, and cerebrospinal fluid biological samples required for the experiment, as well as receive necessary blood or blood product treatment or other necessary medical treatment if necessary for the condition.
• Exclusion Criteria:
• • 1. Suffering from neurodevelopmental disorders other than MECP2 gene functional loss mutations, or pathogenic gene mutations other than MECP2 gene functional loss mutations discovered by whole exome sequencing.
• • 2. Abnormal neurological function caused by traumatic brain injury or suffocation and hypoxia.
• • 3. Through MRI scan, brain tumors or intracranial space-occupying lesions are detected.
• • 4. Comprehensive abnormal psychomotor development has occurred within 6 months after birth.
• • 5. Diagnosed as atypical RTT.
• • 6. Has MECP2 gene mutation, but clinical diagnosis does not match RTT.
• • 7. Need invasive respiratory support.
• • 8. There are contraindications for lumbar puncture or intrathecal injection, including high cerebrospinal fluid pressure, obvious skin infection at the puncture site, trauma, epidural abscess, severe spinal lesions, deformities, spinal cord compression, bleeding tendency (bleeding tendency caused by the use of heparin, warfarin, etc.
• • 9. Have experienced status epilepticus (\>30 minutes) or recurrent unstable seizure control (\>2 generalized seizures per week) in the past 3 months.
• • 10. In addition to RTT, there are other unstable systemic diseases, including active bacteria, fungi, or HIV, hepatitis A, hepatitis B infection.
• • 11. There are significant laboratory indicators with abnormalities: any detection value of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), alkaline phosphatase (ALP) is ≥ 2 times the upper limit of normal (ULN).
• • 12. Total bilirubin ≥ 1.5 × ULN.
• • 13. Creatinine ≥ 159 μ mol/L.
• • 14. Hemoglobin (Hb)\<80g/L.
• • 15. Prothrombin time (PT) prolonged by ≥ 3 seconds.
• • 16. Prolonged activated partial thromboplastin time (APTT) by ≥ 10 seconds.
• • 17. Fasting blood glucose ≥ 7.0 mmol/L.
• • 18. HbA1c≥6.5%.
• • 19. Platelet values are outside the range of 100-300×109/L.
• • 20. Serum anti AAV neutralizing antibody titer\>1:50 (ELISA immunoassay).
• • 21. Systemic use of immunosuppressive drugs (cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immune globulin, and rituximab) other than protocol-specified prophylaxis within 3 months prior to enrollment.
• • 22. Previously received gene therapy.
• • 23. Plan to make changes in clinical medication during this clinical trial, participate in other clinical trials, or have received other investigational drug treatments within 30 days or 5 half lives (whichever is longer) before enrollment.
• • 24. Known allergy to investigational drug.
• • 25. Any condition that, in the opinion of the Investigator, patients are not appropriate to participate in the study.