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

Plain-language summary

This study examines a single-dose gene therapy (AAV-MECP2), given by an injection into the spinal fluid, for its safety, tolerability and efficacy in children with Rett syndrome. Girls aged 4-10 with a typical RTT diagnosis and confirmed loss-of-function mutations in the MECP2 gene may take part. Run by Guangzhou Women and Children's Medical Center, this Early Phase 1 study is active but not currently recruiting.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Early Phase 1

Status

Active, not recruiting

Sponsor

Guangzhou Women and Children's Medical Center

Intervention

Intrathecal injection of AAV-MECP2 for the treatment of Rett syndrome

Start date

1/14/2025

Estimated completion

10/23/2029

Countries

China

Related genes

Locations

• Guangzhou, China

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

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) \< 80 g/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 ×10\^9/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.