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

June 19, 2024 updated by: Shanghai BDgene Co., Ltd.

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 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an open-label, single-dose study of BD211 in patients with transfusion-dependent β-thalassemia aged 3 to 35 years. It is estimated that 9 subjects will be enrolled. BD211 is a gene modified gene therapy product designed to produce healthy β-globin in red blood cells in beta-thalassemia patients. The total follow-up duration was 18 months, the safe endpoints and effectiveness endpoints will be used to assess the safety and efficacy profiles in patients with transfusion-dependent β-thalassemia.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Guandong
      • Guangzhou, Guandong, China, 510120
        • Recruiting
        • Sun Yat-sen Memorial Hospital
        • Contact:
          • Jianpei Fang, M.D.
    • Guangxi
      • Nanning, Guangxi, China, 530021
        • Recruiting
        • The First Affiliated Hospital of Guangxi Medical University
        • Contact:
          • Yongrong Lai, M.D.
    • Shanghai City
      • Shanghai, Shanghai City, China, 200025
        • Recruiting
        • Shanghai Ruijin Hospital, Shanghai Jiaotong University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: BD211 Single-Dose group
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
Genetically modified CD34+ autologous stem cells were transfused intravenously with single dosing.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean time from BD211 treatment to successful neutrophil engraftment, as well as the number and percentage of participants with successful neutrophil engraftment.
Time Frame: 18 months
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.
Time Frame: 18 months
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)
Time Frame: 18 months
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
BD211 transplant-related mortality (TRM) and overall survival (OS) after BD211 treatment.
Time Frame: 18 months
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.
Time Frame: 18 months
RCL positivity rate = number of RCL positive cases ÷ total number of BD211 treatment × 100%.
18 months
Mean duration (days) after participants reached TI
Time Frame: 18 months
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
Time Frame: 18 months
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
Time Frame: 12 months~18months
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
Time Frame: 12 months~18months
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.
Time Frame: 18 months
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
Time Frame: 18 months
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
Time Frame: 18 months
qPCR method were used to measure the VCN level of the BD211 lentivirus vector in peripheral blood.
18 months
Total number of days hospitalized from the discharge day from LAFR to 18 months after BD211 administration
Time Frame: 18 months
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.
Time Frame: 18 months
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
Dose-response relationship
Time Frame: 18 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shanghai BDgene Co., Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sujiang Zhang, M.D., Shanghai Ruijin Hospital, Shanghai Jiaotong University
  • Principal Investigator: Jianpei Fang, M.D., Sun Yat-sen Memorial Hospital,Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 5, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 12, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 13, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 20, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 24, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 19, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BD-TDT-211005

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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