Gene therapy for treating β-thalassemia Major

A Phase 1 Clinical Trail of the Safety and Efficacy of Gene-modified Autologous Hematopoietic Stem Cell (BD211) Intravenous Infusion for the Treatment of Transfusion-dependent β-thalassaemia Patients

This study is testing a new gene therapy to see if it can safely help young people with severe β-thalassemia reduce their need for blood transfusions.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 3 Years to 35 Years
• Sex: All
• Sponsor: Shanghai BDgene Co., Ltd. (industry)
• Locations: 3 sites (Guangzhou, Guandong and 2 other locations)
• Trial ID: NCT06465550 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of a gene-modified autologous hematopoietic stem cell therapy called BD211 in patients with transfusion-dependent β-thalassemia. It involves a single-dose administration following myeloablative preconditioning, with a focus on engraftment efficacy and tolerability. The trial will enroll approximately 9 participants aged 3 to 35 years, who will be monitored for 18 months to assess the therapy's safety and efficacy profiles.

Who should consider this trial

Good fit: Ideal candidates are children and young adults aged 3 to 18 years with transfusion-dependent β-thalassemia who are eligible for hematopoietic stem cell transplantation but lack a suitable donor.

Not a fit: Patients who are not transfusion-dependent or those who have access to a suitable donor for allogeneic stem cell transplantation 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 treatment.

Eligibility criteria

Inclusion Criteria:

1. Participants aged 3 years (inclusive) to 18 years (exclusive), with no gender restrictions.
2. Parents/legal guardians have fully understood and voluntarily signed a written informed consent form; and it is recommended that children aged 8 and above be involved in the decision to participate in this clinical trial and obtain a written consent form.
3. Transfusion-dependent β-thalassemia patients. "Transfusion-dependent" is defined as: requiring at least 100 mL/kg of packed red blood cells annually; the genotype can be β0/β0, β0/β+, or β+/β+, diagnosed through hemoglobin studies.
4. Eligible for allogeneic hematopoietic stem cell transplantation, but without a donor or those refusing to undergo allogeneic hematopoietic stem cell transplantation.
5. Have undergone symptomatic treatment for at least the past 2 years and have retained medical records including transfusion history.
6. Stable condition and maintained an appropriate iron chelation regimen.
7. Good status of organ function.
8. Good compliance from the individual and parents/legal guardians, willing to adhere to visit schedules, trial plans, laboratory tests, and other trial procedures as stipulated in this protocol.
9. Willing to participate in long-term follow-up research.

Exclusion Criteria:

1. Has a fully HLA-matched hematopoietic stem cell donor and is willing to receive a fully HLA-matched hematopoietic stem cell transplant. Enrollment is otherwise only advised after review by the safety review committee.
2. Positive for antibodies against Human Immunodeficiency Virus 1/2 (HIV-1/HIV-2), Treponema pallidum (TP) specific antibodies, Human T-lymphotropic Virus 1 or 2 (HTLV-1/HTLV-2) antibodies, and Vesicular Stomatitis Virus G (VSV-G).
3. Positive for Hepatitis B Virus (HBV) HbsAg or HBV-DNA; Hepatitis C Virus (HCV) HCAb positive; positive nucleic acid test for Epstein-Barr Virus (EBV) or Cytomegalovirus (CMV).
4. Severe active bacterial, viral, fungal, malarial, or parasitic infections.
5. Has had, or currently has, a malignant, myeloproliferative, or immunodeficiency disorder.
6. Direct relatives with known or suspected hereditary cancer syndromes (including but not limited to breast cancer, colorectal cancer, ovarian cancer, prostate cancer, and pancreatic cancer).
7. Autoimmune diseases that could result in transfusion difficulties.
8. Major organ diseases or abnormal lab tests, including:

   1. Liver cirrhosis, fibrosis, or active hepatitis, and/or abnormal liver function tests (Serum total bilirubin (TBIL) ≥ 1.5x Upper Limit of Normal (ULN); Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≥ 2.5x ULN; Alkaline phosphatase ≥ 2.5x ULN).
   2. Heart disease, or Left Ventricular Ejection Fraction (LVEF) \< 60%.
   3. Kidney diseases, or serum creatinine ≥ 1.5ULN, creatinine clearance rate \< 30% of the normal level (measured or calculated by the Cockcroft-Gault equation).
   4. Endocrine disorders, such as insulin-dependent diabetes, hyperthyroidism, or hypothyroidism.
   5. Severe iron overload, serum ferritin ≥ 5000 ng/mL.
   6. Cardiac T2\* \< 20 ms, and/or liver iron content (LIC) ≥ 15mg/g liver weight by MRI.
   7. Significant pulmonary hypertension diagnosed clinically according to guidelines, requiring clinical medical intervention.
9. Uncorrected bleeding disorders.
10. Severe psychiatric disorders.
11. Peripheral blood white cell (WBC) count \< 3x10\^9/L or platelets count \< 120x10\^9/L.
12. Received hydroxyurea treatment within the last 3 months before stem cell collection.
13. Used erythropoiesis-stimulating agents within the 3 months prior to HSC collection.
14. History of allogeneic transplantation.
15. Previously received any type of gene and/or cell therapy.
16. Participating in another clinical trial and is within a 30-day screening period.
17. Has contraindications to anesthesia.
18. Has contraindications to hematopoietic stem cell collection.
19. Allergic to the investigational drug or its excipients.
20. Any other conditions determined by the investigator as unsuitable for participation in this clinical trial.

Where this trial is running

Guangzhou, Guandong and 2 other locations

• Sun Yat-sen Memorial Hospital — Guangzhou, Guandong, China (RECRUITING)
• The First Affiliated Hospital of Guangxi Medical University — Nanning, Guangxi, China (RECRUITING)
• Shanghai Ruijin Hospital, Shanghai Jiaotong University — Shanghai, Shanghai City, China (RECRUITING)

Study contacts

• Principal investigator: Sujiang Zhang, M.D. — Shanghai Ruijin Hospital, Shanghai Jiaotong University
• Study coordinator: fujun Li

Conditions: β-thalassemia