Gene therapy using modified stem cells for treating β-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 β-thalassemia reduce their need for blood transfusions.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 6 Years to 35 Years
• Sex: All
• Sponsor: Shanghai BDgene Co., Ltd. (industry)
• Locations: 1 site (Shanghai)
• Trial ID: NCT05776173 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 with a lentiviral vector to produce healthy β-globin in patients with transfusion-dependent β-thalassemia. The trial is open-label and will enroll approximately 10 participants aged 6 to 35 years. Participants will undergo myeloablative preconditioning before receiving the stem cell transplant, and they will be monitored for safety and effectiveness over a 24-month follow-up period.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 6 to 35 years with transfusion-dependent β-thalassemia who meet specific genetic and health criteria.

Not a fit: Patients who are eligible for allogeneic hematopoietic stem cell transplantation or have certain genetic abnormalities may not benefit from this study.

Why it matters

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

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

Eligibility criteria

Inclusion Criteria:

1. Ages 6 to 35 years old, including:

   Subjects should be able to provide an ICF. 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. The tumor genes chip detection results about acute leukemia and myeloid tumor gene mutations (panel) showed no abnormality.
3. There were candidates for HLA gene semi-compatible hematopoietic stem cell transplantation.
4. No eligiblity for allogeneic hematopoietic stem cell transplantation.
5. The treatment of erythrocyte maturation agent luspatercept cannot be financially supported.
6. The investigator confirmed that subject was willing to follow the research procedures.
7. 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. Pregnant or postpartum nursing or unable to use contraception.
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. Any other conditions being ineligible for HSC transplantation determined by the investigator.
15. The subject involved with another clinical study in a 30-day screening period.
16. Subjects who expected to become parents during the 27-month study period.
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.

Where this trial is running

Shanghai

• Shanghai Ruijin Hospital — Shanghai, China (RECRUITING)

Study contacts

• Principal investigator: Sujiang Zhang, M.D. — Ruijin Hospital, Shanghai, China
• Study coordinator: Sujiang Zhang, M.D.

Conditions: β-thalassemia Major