A Phase 1 Study of Gene-modified Autologous Hematopoietic Stem Cell (BD211) Treating β-thalassemia Major

NCT06465550 | Recruiting Phase 1

• 1 other identifier: BD-TDT-211005
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

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

Outcome Measures

Primary Outcomes (3)

• Mean time from BD211 treatment to successful neutrophil engraftment, as well as the number and percentage of participants with successful neutrophil engraftment.

  Definition of successful neutrophil engraftment: A consistent absolute neutrophil count (ANC) recovery of ≥0.5×10\^9/L over three consecutive days.

  18 months

• Mean time from BD211 treatment to successful platelet engraftment, as well as the number and percentage of participants with successful platelet engraftment.

  Definition of successful platelet engraftment: No platelet transfusion for 7 days with platelet counts of ≥20×10\^9/L in three consecutive measurements.

  18 months

• Proportion of participants achieving transfusion independence (TI)

  TI defined as "hemoglobin (Hb) ≥ 90g/L without any transfusion of packed red blood cells (pRBCs) for 12 months at any time during the study period after BD211 treatment"; proportion of participants with TI = number of participants with TI ÷ total number of BD211 treatment.

  18 months

Secondary Outcomes (12)

• BD211 transplant-related mortality (TRM) and overall survival (OS) after BD211 treatment.

  18 months

• Incidence of aberrant replication competent lentivirus (RCL) or malignant transformation induced by vector insertion after BD211 treatment.

  18 months

• Total number of days hospitalized from the discharge day from LAFR to 18 months after BD211 administration

  18 months

• Types, numbers and incidence rate of adverse events (AEs) and serious adverse events (SAEs) that occurred within 18 months after BD211 adminstration.

  18 months

• Mean duration (days) after participants reached TI

  18 months

Study Arms (1)

BD211 Single-Dose group

EXPERIMENTAL

Route of Administrate: infusion intravenously. Dosage form: injection solution. Dose: ≥ 5×10\^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: 3 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants aged 3 years (inclusive) to 18 years (exclusive), with no gender restrictions.
• 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.
• 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.
• Eligible for allogeneic hematopoietic stem cell transplantation, but without a donor or those refusing to undergo allogeneic hematopoietic stem cell transplantation.
• Have undergone symptomatic treatment for at least the past 2 years and have retained medical records including transfusion history.
• Stable condition and maintained an appropriate iron chelation regimen.
• Good status of organ function.
• 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.
• Willing to participate in long-term follow-up research.

You may not qualify if:

• 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.
• 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).
• 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).
• Severe active bacterial, viral, fungal, malarial, or parasitic infections.
• Has had, or currently has, a malignant, myeloproliferative, or immunodeficiency disorder.
• 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).
• Autoimmune diseases that could result in transfusion difficulties.
• Major organ diseases or abnormal lab tests, including:
• 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).
• Heart disease, or Left Ventricular Ejection Fraction (LVEF) \< 60%.
• Kidney diseases, or serum creatinine ≥ 1.5ULN, creatinine clearance rate \< 30% of the normal level (measured or calculated by the Cockcroft-Gault equation).
• Endocrine disorders, such as insulin-dependent diabetes, hyperthyroidism, or hypothyroidism.
• Severe iron overload, serum ferritin ≥ 5000 ng/mL.
• Cardiac T2\* \< 20 ms, and/or liver iron content (LIC) ≥ 15mg/g liver weight by MRI.
• Significant pulmonary hypertension diagnosed clinically according to guidelines, requiring clinical medical intervention.

Sponsors & Collaborators

• Shanghai BDgene Co., Ltd.: lead

Study Sites (3)

Sun Yat-sen Memorial Hospital

Guangzhou, Guandong, 510120, China

RECRUITING

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530021, China

RECRUITING

Shanghai Ruijin Hospital, Shanghai Jiaotong University

Shanghai, Shanghai City, 200025, China

RECRUITING

Study Officials

• Sujiang Zhang, M.D.

  Shanghai Ruijin Hospital, Shanghai Jiaotong University

  PRINCIPAL INVESTIGATOR

• Jianpei Fang, M.D.

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

fujun Li

CONTACT

+86-19121311061; fujun.li@bdgene.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2024
• First Posted: June 20, 2024
• Study Start: January 5, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 24, 2024

Record last verified: 2024-06

Locations

CN (3)