A Phase 1 Study of Gene-modified Autologous Hematopoietic Stem Cell (BD211) Treating β-thalassemia Major
NCT Number: NCT06465550
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: β-thalassemia
Interventions: GENETIC: BD211
Sponsor: Shanghai BDgene Co., Ltd.
Sex: ALL
Age: CHILD, ADULT
Enrollment: 9
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-01-05
Completion Date: 2026-12
Locations: Sun Yat-sen Memorial Hospital, Guangzhou, Guandong, 510120, China|The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China|Shanghai Ruijin Hospital, Shanghai Jiaotong University, Shanghai, Shanghai City, 200025, China

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.

Primary Outcome Measures: 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 Outcome Measures: BD211 transplant-related mortality (TRM) and overall survival (OS) after BD211 treatment., TRM = number of BD211 transplant-related deaths ÷ total number of BD211 treatment x 100% OS = number of all-cause deaths after BD211 treatment ÷ total number of BD211 treatment x 100%, 18 months|Incidence of aberrant replication competent lentivirus (RCL) or malignant transformation induced by vector insertion after BD211 treatment., RCL positivity rate = number of RCL positive cases ÷ total number of BD211 treatment × 100%., 18 months|Total number of days hospitalized from the discharge day from LAFR to 18 months after BD211 administration, The number of days of all-cause hospitalisation was calculated for each participant from the start of discharge from the transplantation unit after successful neutrophil and platelet engraftment to 18 months after BD211 treatment ., 18 months|Types, numbers and incidence rate of adverse events (AEs) and serious adverse events (SAEs) that occurred within 18 months after BD211 adminstration., AEs and SAEs were evaluated per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.The frequency, severity, and correlation of AEs and SAEs with the investigational drug based on laboratory results and clinical manifestations were determined., 18 months|Mean duration (days) after participants reached TI, Mean duration after reaching TI = sum of duration after reaching TI for all participants ÷ total number of participants., 18 months|Mean time required from BD211 treatment (D0) to achieve TI, Mean time required from BD211 treatment (D0) to achieve TI = sum of time required from BD211 infusion (D0) to achieve TI ÷ total number of participants., 18 months|Mean Hb values after BD211 treatment, Mean Hb of participants per month = sum of Hb (g/L) values of all participants per month ÷ total number of participants, 12 months~18months|Proportion of participants with 60% and 80% reduction in blood transfusions from baseline, The mean blood transfusion volume (mL/kg/year) in the 2 years prior to enrolment was used as the baseline, and compared with the mean blood transfusion volume (mL/kg/year) in the M12\~M18 period after receiving the BD211 infusion, and the proportion of participants whose blood transfusion volume was reduced by 60% and 80%, respectively, was calculated., 12 months~18months|Change in ferritin levels from baseline., Change in mean serum ferritin levels compared to baseline values at 6 months, 12 months and 18 months after BD211 treatment., 18 months|Expression of βA-T87Q globin protein in whole blood, HPLC method was used to measure the expression of βA-T87Q globin protein in peripheral blood., 18 months|Mean VCN of the BD211 lentivirus vector in peripheral blood, qPCR method were used to measure the VCN level of the BD211 lentivirus vector in peripheral blood., 18 months|Dose-response relationship, The relationship between the BD211 dose and efficacy endpoints including TI outcome and expressed level of βA-T87Q globin protein (primarily PD biomarker) in blood were analyzed., 18 months