Safety and Efficacy of Gene Modified Autologous Hematopoietic Stem Cells to Treat Transfusion-dependent Beta-thalassemia

This is an open-label, single-dose study of BD211 in patients with transfusion-dependent β-thalassemia aged 3 to 18 years. It is estimated that 10 subjects will be enrolled. BD211 is a gene modified gene therapy product designed to produce healthy β-globin in red blood cells in beta-thalassemia patients. The total follow-up duration was 24 months, the safe endpoints and effectiveness endpoints will be used to assess the safety and efficacy profiles in patients with transfusion-dependent β-thalassemia.

Inclusion criteria

• Ages 3 to 18 years old, including:

The parents or legal guardians must be able to understand and provide ICFs. If available, it is strongly recommended that children aged ≥8 years in treatment decisions and obtain written ICFs and be clearly documented; Diagnosed as Transfusion Dependent β-thalassemia with any genotype (β0, β+, βE/β0, βS/S, βS/β0, βS/β+), confirmed the Hb analysis. No alfa chain genetic abnormalities. Subjects must stabilize and maintain an appropriate iron chelation regimen. Transfusion-dependent types are defined as requiring at least 100 mL/kg/ year of red blood cells (pRBCs).

• No eligiblity for allogeneic hematopoietic stem cell transplantation.
• The treatment of erythrocyte maturation agent luspatercept cannot be financially supported.
• The subjects' parents/legal guardians must be willing and able to follow the study procedures in the study protocol.
• Good organs' functions.
• Having complete medical records including a history of blood transfusions testified subject received treatment and followed up for at least two years prior to screening .

Exclusion criteria

• Availability of voluntary, fully HLA-matched hematopoietic cell donors, unless recommended for inclusion by the Monitoring Committee.
• HIV-1 and HIV-2 were positive, and / or HTLV-1, HTLV-2 and VSV-G antibodies were positive.
• An active bacterial, viral, fungal or parasitic infection.
• Contraindicated for the extraction of bone marrow under anesthesia.
• Any malignancy, myeloproliferative, or immunodeficient disease and relevant medical history.
• Peripheral blood white blood cell (WBC) count < 3×10^9/L or platelet count < 120×10^9/L.
• A history of allo-transplantation.
• Erythropoietin was used within 3 months prior to HSC cell collection.
• Immediate family members with known or suspected familial cancer syndromes (including but not limited to breast, colorectal, ovarian, prostate, and pancreatic cancers).
• Subjects with a diagnosis of major mental illness may had a serious disability to participate in the study.
• Active recurrent malaria.
• Had autoimmune diseases that may make blood transfusions difficult.
• History of major organ injury including:

Liver disease, transaminase > 3 times the upper limit of normal. (If the liver biopsy does not reveal evidence of widespread bridging fibrosis, cirrhosis, or acute hepatitis, this indicator will not be used as a criterion for the exclusion); Widely bridging fibrosis, histopathological evidence of acute hepatitis or cirrhosis showed in liver biopsy Heart disease, left ventricular ejection fraction < 25%; Kidney disease, creatinine clearance < 30% normal level; Of severe iron overload, confirmed by the study doctor; An heart MRI detection of T2 * < 10 ms; Significant pulmonary hypertension needing clinical medical intervention.

• There are bleeding diseases that have not been cured.
• The subject involved with another clinical study in a 30-day screening period.
• Allergic to the research drug and its excipients.
• Prior treatment with any type of gene and/or cell therapy.
• As assessed by the investigator, the subjects or their parents are unable to comply well with the study procedures per protocol.
• Hydroxyurea treatment within 3 months prior to hematopoietic stem cell collection.
• Had diseases that interfere with hematopoietic stem cells collections.
• Any other conditions being ineligible for HSC transplantation determined by the investigator.