Gene therapy using modified stem cells for treating beta-thalassemia

Safety and Efficacy of Lentiviral Vector Transduction of β-globin Genetically Modified Autologous CD34+ Hematopoietic Stem Cells in Patients With Transfusion-dependent β-thalassemia

This study is testing a new gene therapy using modified stem cells to see if it can help young people with beta-thalassemia reduce their need for blood transfusions.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 3 Years to 18 Years
• Sex: All
• Sponsor: Shanghai BDgene Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Shanghai)
• Trial ID: NCT05773729 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of a gene therapy product called BD211, which involves the transplantation of autologous CD34+ hematopoietic stem cells modified to produce healthy β-globin in patients with transfusion-dependent β-thalassemia. The trial is open-label and will enroll approximately 10 participants aged 3 to 18 years. Participants will undergo myeloablative preconditioning before receiving the stem cell transplant, and their progress will be monitored over a 24-month follow-up period to assess both safety and effectiveness.

Who should consider this trial

Good fit: Ideal candidates are children and adolescents aged 3 to 18 years with transfusion-dependent β-thalassemia who are not eligible for allogeneic stem cell transplantation.

Not a fit: Patients with alfa chain genetic abnormalities or those who can financially support the treatment of erythrocyte maturation agents like luspatercept may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce or eliminate the need for blood transfusions in patients with beta-thalassemia.

How similar studies have performed: Other studies using gene therapy for beta-thalassemia have shown promising results, indicating potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. 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).
2. No eligiblity for allogeneic hematopoietic stem cell transplantation.
3. The treatment of erythrocyte maturation agent luspatercept cannot be financially supported.
4. The subjects' parents/legal guardians must be willing and able to follow the study procedures in the study protocol.
5. Good organs' functions.
6. 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:

1. Availability of voluntary, fully HLA-matched hematopoietic cell donors, unless recommended for inclusion by the Monitoring Committee.
2. HIV-1 and HIV-2 were positive, and / or HTLV-1, HTLV-2 and VSV-G antibodies were positive.
3. An active bacterial, viral, fungal or parasitic infection.
4. Contraindicated for the extraction of bone marrow under anesthesia.
5. Any malignancy, myeloproliferative, or immunodeficient disease and relevant medical history.
6. Peripheral blood white blood cell (WBC) count \< 3×10\^9/L or platelet count \< 120×10\^9/L.
7. A history of allo-transplantation.
8. Erythropoietin was used within 3 months prior to HSC cell collection.
9. Immediate family members with known or suspected familial cancer syndromes (including but not limited to breast, colorectal, ovarian, prostate, and pancreatic cancers).
10. Subjects with a diagnosis of major mental illness may had a serious disability to participate in the study.
11. Active recurrent malaria.
12. Had autoimmune diseases that may make blood transfusions difficult.
13. 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.
14. There are bleeding diseases that have not been cured.
15. The subject involved with another clinical study in a 30-day screening period.
16. Allergic to the research drug and its excipients.
17. Prior treatment with any type of gene and/or cell therapy.
18. As assessed by the investigator, the subjects or their parents are unable to comply well with the study procedures per protocol.
19. Hydroxyurea treatment within 3 months prior to hematopoietic stem cell collection.
20. Had diseases that interfere with hematopoietic stem cells collections.
21. Any other conditions being ineligible for HSC transplantation determined by the investigator.

Where this trial is running

Shanghai

• Shanghai Children's Medical Centre — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Chen Jing, M.D. — Shanghai Children's Medical Center
• Study coordinator: Chen Jing, M.D.

Conditions β-thalassemia