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

NCT05776173 | Recruiting

• 1 other identifier: BD-TDT-211002
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be intented to evaluate the safety, tolerability, and engraftment efficacy after myeloablative preconditioning and transplantation of autologous CD34+ hematopoietic stem cells transduced with a lentiviral vector encoding the human βA-T87Q-globin gene in patients with transfusion-dependent (TDT) β-thalassemia.

Conditions

β-thalassemia Major

Outcome Measures

Primary Outcomes (2)

• Red blood cell (RBCs) transfusion requirements, whether reaching TI

  Comparison of blood volume and number of transfusions in the 2 years prior to participants enrolment as baseline with blood volume and number of transfusions up to months 6, 12, and 24 after receiving transfusion of the BD211. TI defined as peripheral blood weighted average hemoglobin (Hb) \> or = 9 g/dL without pRBCs transfusion for 60 days after BD211 treatment, and transfusion is continuously halted for 12 months.

  24 months

• Total hospitalizing days at 6, 12, and 24 months (discharge after transplant)

  Total hospitalizing days at 6, 12, and 24 months after transplantation were counted.

  24 months

Secondary Outcomes (10)

• Percentage of treated participants with Transfusion-Dependent β-Thalassemia (TDT) who achieved transfusion independence for at least 6 months

  24 months

• Change in RBCs infusion from baseline at 6 to 24 months

  24 months

• Mean Hb (g/dL) at 6, 12 and 24 months after treatment

  24 months

• Change in ferritin/liver iron levels from baseline

  24 months

• Neutrophil engraftment, platelet engraftment and vector copy number

  24 months

Study Arms (1)

BD211 Single-Dose group

EXPERIMENTAL

Route of Administrate: infusion intravenously. Dosage form: injection solution. Dose: 5×10\^6 cells /kg \~ 10×10\^6 cells /kg. Frequency of administration: One dosing intravenously. Intervention: Single dose of BD211

Genetic: BD211

Interventions

BD211 GENETIC

Genetically modified CD34+ autologous stem cells were transfused intravenously with single dosing.

BD211 Single-Dose group

Eligibility Criteria

• Age: 6 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).
• The tumor genes chip detection results about acute leukemia and myeloid tumor gene mutations (panel) showed no abnormality.
• There were candidates for HLA gene semi-compatible hematopoietic stem cell transplantation.
• No eligiblity for allogeneic hematopoietic stem cell transplantation.
• The treatment of erythrocyte maturation agent luspatercept cannot be financially supported.
• The investigator confirmed that subject was willing to follow the research procedures.
• 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.

You may not qualify if:

• 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.
• Pregnant or postpartum nursing or unable to use contraception.
• History of major organ injury including:
• Any other conditions being ineligible for HSC transplantation determined by the investigator.
• The subject involved with another clinical study in a 30-day screening period.
• Subjects who expected to become parents during the 27-month study period.

Sponsors & Collaborators

• Shanghai BDgene Co., Ltd.: lead
• Ruijin Hospital: collaborator

Study Sites (1)

Shanghai Ruijin Hospital

Shanghai, 200025, China

RECRUITING

Study Officials

• Sujiang Zhang, M.D.

  Ruijin Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sujiang Zhang, M.D.

CONTACT

+86-17717285030; zbruce.zhang@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2023
• First Posted: March 20, 2023
• Study Start: August 10, 2023
• Primary Completion: March 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: June 14, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)