β-thalassemiaPhase 1NCT06465550
A Phase 1 Study of Gene-modified Autologous Hematopoietic Stem Cell (BD211) Treating β-thalassemia Major
A Phase 1 study testing BD211 in people with β-thalassemia, run by Shanghai BDgene Co., Ltd. at 3 sites in China.
Trial 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)… Read more about this study
- Who is it for?
- Ages 3 to 35 years
- Conditions the study is for
- β-thalassemia
- What is being tested?
- BD211
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 3 sitesChina
- Study dates
- 5 Jan 2024to Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
- Uncorrected bleeding disorders.
- Severe psychiatric disorders.
- Peripheral blood white cell (WBC) count < 3x10^9/L or platelets count < 120x10^9/L.
- Received hydroxyurea treatment within the last 3 months before stem cell collection.
- Used erythropoiesis-stimulating agents within the 3 months prior to HSC collection.
- History of allogeneic transplantation.
- Previously received any type of gene and/or cell therapy.
- Participating in another clinical trial and is within a 30-day screening period.
- Has contraindications to anesthesia.
- Has contraindications to hematopoietic stem cell collection.
- Allergic to the investigational drug or its excipients.
- Any other conditions determined by the investigator as unsuitable for participation in this clinical trial.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites, 3 recruiting
- Recruiting
Sun Yat-sen Memorial Hospital
Guangzhou, Guandong, 510120
Jianpei Fang, M.D.
- Recruiting
The First Affiliated Hospital of Guangxi Medical University
Nanning, Guangxi, 530021
Yongrong Lai, M.D.
- Recruiting
Shanghai Ruijin Hospital, Shanghai Jiaotong University
Shanghai, Shanghai City, 200025
Sujiang zhang, M.D., +86-17717285030, zbruce.zhang@hotmail.com
About this study
Official title: 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.
Read the 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.
- Conditions
- β-thalassemia
- Being tested
- BD211
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BD211Genetic
Genetically modified CD34+ autologous stem cells were transfused intravenously with single dosing.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Genetic: BD211 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 18 months
Secondary outcomes (12)
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%
Measured: 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%.
Measured: 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 .
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2024
- Study start5 Jan 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for β-thalassemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai BDgene Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sujiang Zhang, M.D., Principal investigator, Shanghai Ruijin Hospital, Shanghai Jiaotong UniversityJianpei Fang, M.D., Principal investigator, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06465550
- Sponsor's protocol ID
- BD-TDT-211005
- Status last verified
- Jun 2024
- First submitted
- 12 Jun 2024
- Last updated
- 24 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06465550
- Acronym / sponsor ID
- BD-TDT-211005
- Conditions
- β-thalassemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Shanghai BDgene Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 5 Jan 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 20 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BD211 Single-Dose group | Experimental | Genetic: BD211Route 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 |
Who may qualify
- Ages
- 3 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BD211Genetically modified CD34+ autologous stem cells were transfused intravenously with single dosing. | Genetic | BD211 Single-Dose group |
Primary outcome
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.
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.
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.
12 secondary outcomes
BD211 transplant-related mortality (TRM) and overall survival (OS) after BD211 treatment.
Time frame: 18 months
Incidence of aberrant replication competent lentivirus (RCL) or malignant transformation induced by vector insertion after BD211 treatment.
Time frame: 18 months
Total number of days hospitalized from the discharge day from LAFR to 18 months after BD211 administration
Time frame: 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
Mean duration (days) after participants reached TI
Time frame: 18 months
Mean time required from BD211 treatment (D0) to achieve TI
Time frame: 18 months
Mean Hb values after BD211 treatment
Time frame: 12 months~18months
Proportion of participants with 60% and 80% reduction in blood transfusions from baseline
Time frame: 12 months~18months
Change in ferritin levels from baseline.
Time frame: 18 months
Expression of βA-T87Q globin protein in whole blood
Time frame: 18 months
Mean VCN of the BD211 lentivirus vector in peripheral blood
Time frame: 18 months
Dose-response relationship
Time frame: 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sujiang Zhang, M.D. principal investigator
Shanghai Ruijin Hospital, Shanghai Jiaotong University
Jianpei Fang, M.D. principal investigator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BD211 in people with β-thalassemia, run by Shanghai BDgene Co., Ltd. at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact fujun Li (+86-19121311061, fujun.li@bdgene.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2024.