An Open-label Study of a Gene Therapy Product (Vebeglogene Autotemcel) in Transfusion Dependent Beta-Thalassemia

An Open-label Clinical Trial of Ex Vivo Beta-globin Lentiviral Vector Transduction of Autologous CD34+HSPCs (Vebeglogene Autotemcel) for the Treatment of Transfusion Dependent Beta-thalassemia Patients

This is an interventional study to evaluate the safety and efficacy of autologous Hematopoietic Stem and Progenitor Cells (HSPCs) transduced with lentiviral vector encoding functional hemoglobin subunit beta (HBB) gene in patients with transfusion-dependent beta-thalassemia.

The participant's autologous HSPCs will be transduced with the self-inactivating lentiviral vector, carrying the functional HBB gene.

Study duration per participant is approximately 27 months including an approximately 30-day screening/baseline period, an approximately 60-day mobilization and product manufacture, an approximately 10-day myeloablative conditioning, 1 treatment day, and an approximately 24-month study observation period.

The endpoints will be used to assess the safety and efficacy profiles in patients with transfusion-dependent beta-thalassemia.

Inclusion Criteria:

• Patients or parent(s)/legal guardian(s) willing and able to complete the informed consent process and comply with study procedures and visit schedules.
• Diagnosis of beta-thalassemia and a history of RBCs transfusions.
• Documented baseline, or pretransfusion, Hb≤7 g/dL.
• Availability of an adequate and well-documented transfusion history.

Exclusion Criteria:

• Active bacterial, viral, fungal, or parasitic infection.
• A white blood cell (WBC) counts<3×10^9/L, and/or platelet counts<100×10^9/L not related to hypersplenism.
• Uncorrected bleeding disorder.
• Presence of severe diseases that judged not compatible with the study procedures, such as severe hepatic disease, kidney disease, lung disease, and/or cardiovascular disease.
• Uncontrolled seizure disorder.
• Any evidence of severe iron overload that, in the investigator's opinion, warrants exclusion.
• Prior autologous hematopoietic stem cell transplantation.
• Prior receipt of gene therapy.