β-thalassemia MajorNCT05776173
Safety and Efficacy of Gene Modified Autologous Hematopoietic Stem Cells to Treat Transfusion-dependent β-thalassemia
A study testing BD211 in people with β-thalassemia Major, run by Shanghai BDgene Co., Ltd. at 1 site 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 6 to 35 years
- Conditions the study is for
- β-thalassemia Major
- 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
- 10 participants
- Where
- 1 siteChina
- Study dates
- 10 Aug 2023to Oct 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 6 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- Availability of voluntary, fully HLA-matched hematopoietic cell donors, unless recommended for inclusion by the Monitoring Committee.
- 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.
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- 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:
- Liver disease, transaminase > 3 times the upper limit of normal. (If the liver biopsy does not reveal evidence of widespread bridging fibrosis, cirrhosis, or acute hepatitis, this indicator will not be used as a criterion for the exclusion); Widely bridging fibrosis, histopathological evidence of acute hepatitis or cirrhosis showed in liver biopsy Heart disease, left ventricular ejection fraction < 25%; Kidney disease, creatinine clearance < 30% normal level; Of severe iron overload, confirmed by the study doctor; An heart MRI detection of T2 < 10 ms; Significant pulmonary hypertension needing clinical medical intervention.
- 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.
- Prior treatment with any type of gene and/or cell therapy.
- As assessed by the investigator, the subjects or their parents are unable to comply well with the study procedures per protocol.
- Hydroxyurea treatment within 3 months prior to hematopoietic stem cell collection.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Ruijin Hospital
Shanghai, 200025
Sujiang Zhang, M.D., +86-17717285030, zbruce.zhang@hotmail.com
About this study
Official title: Safety and Efficacy of Lentiviral Vector Transduction of β-globin Genetically Modified Autologous CD34+ Hematopoietic Stem Cells in Patients With Transfusion-dependent β-thalassemia
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 6 to 35 years. It is estimated that 10 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 24 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 Major
- 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 ~ 10×10^6 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.
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.
Measured: 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.
Measured: 24 months
Secondary outcomes (10)
Percentage of treated participants with Transfusion-Dependent β-Thalassemia (TDT) who achieved transfusion independence for at least 6 months
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.
Measured: 24 months
Change in RBCs infusion from baseline at 6 to 24 months
The quantity of RBCs transfusions at 6 to 24 months will be measured and compared with baseline level.
Measured: 24 months
Mean Hb (g/dL) at 6, 12 and 24 months after treatment
Mean Hb (g/dL) in 6, 12, and 24 months after drug product infusion are tested and calculated.
Measured: 24 months
Change in ferritin/liver iron levels from baseline
The Ferritin/liver iron levels are assayed per protocol plan, and evaluate the changes from those baseline level.
Measured: 24 months
Neutrophil engraftment, platelet engraftment and vector copy number
Neutrophil engraftment was defined as the first of absolute neutrophil count (ANC) > or = 0.5 ×10^9/ L for 3 consecutive days (or 3 consecutive measurements done on separate days), after a post-transplant value less than (<) 0.5 × 10^9/L.
Platelet engraftment was defined as the first of 3 consecutive platelet values > or =20 × 10^9/L for participants on different days with no platelet transfusionsadministered for 7 days immediately preceding. The day of engraftment is the first day of the 3 consecutive platelet measurements.
Vector copy number will be detected per investigating time schedule.
Measured: 24 months
Transplant-related mortality in 3 months and 12 months
Transplant related mortality was definedas any death occurring in the study post drug product infusion deemed related to the transplant bythe investigator.
Measured: 12 months
Overall survival
Overall survival was defined as time from date of BD211 Drug Product infusion (Day 1) to date of death. Overall survival was censored at the date of last visit if the participant was still alive.
Measured: 24 months
RCL incidence
Subjects blood RCL was detected with specific assay method, and the incidence was calculated at different scheduled timeslots.
Measured: 24 months
Characterized insertion mutagenesis events that lead to clonal dominance or leukemia
The number of insertion mutagenesis events that characterized clonal dominance or leukemia was collected.
Measured: 24 months
Frequency and severity of AE
An AE was any untoward medical occurrence associated with the use of a drug in participants, whether or not considered drug related. An AE may include a change in physical signs, symptoms, and/or clinically significant laboratory change occurring in any phase of a clinical study.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2023
- Study start10 Aug 2023
- Primary completionMar 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for β-thalassemia MajorStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai BDgene Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ruijin Hospital
- Responsible party
- Sponsor
- Investigators
- Sujiang Zhang, M.D., Principal investigator, Ruijin Hospital, Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05776173
- Sponsor's protocol ID
- BD-TDT-211002
- Status last verified
- Jun 2024
- First submitted
- 3 Mar 2023
- Last updated
- 14 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Lentiviral Vector Transduction of β-globin Genetically Modified Autologous CD34+ Hematopoietic Stem Cells in Patients With Transfusion-dependent β-thalassemia
- ClinicalTrials.gov ID
- NCT05776173
- Acronym / sponsor ID
- BD-TDT-211002
- Conditions
- β-thalassemia Major
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Shanghai BDgene Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Ruijin Hospital
- Study start
- 10 Aug 2023 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 20 Mar 2023 (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 6 to 35 years. It is estimated that 10 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 24 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 ~ 10×10^6 cells /kg. Frequency of administration: One dosing intravenously. Intervention: Single dose of BD211 |
Who may qualify
- Ages
- 6 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (20 listed)
- Availability of voluntary, fully HLA-matched hematopoietic cell donors, unless recommended for inclusion by the Monitoring Committee.
- 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.
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
Red blood cell (RBCs) transfusion requirements, whether reaching TI
Time frame: 24 months
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.
Total hospitalizing days at 6, 12, and 24 months (discharge after transplant)
Time frame: 24 months
Total hospitalizing days at 6, 12, and 24 months after transplantation were counted.
10 secondary outcomes
Percentage of treated participants with Transfusion-Dependent β-Thalassemia (TDT) who achieved transfusion independence for at least 6 months
Time frame: 24 months
Change in RBCs infusion from baseline at 6 to 24 months
Time frame: 24 months
Mean Hb (g/dL) at 6, 12 and 24 months after treatment
Time frame: 24 months
Change in ferritin/liver iron levels from baseline
Time frame: 24 months
Neutrophil engraftment, platelet engraftment and vector copy number
Time frame: 24 months
Transplant-related mortality in 3 months and 12 months
Time frame: 12 months
Overall survival
Time frame: 24 months
RCL incidence
Time frame: 24 months
Characterized insertion mutagenesis events that lead to clonal dominance or leukemia
Time frame: 24 months
Frequency and severity of AE
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2024.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Sujiang Zhang, M.D. principal investigator
Ruijin Hospital, Shanghai, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing BD211 in people with β-thalassemia Major, run by Shanghai BDgene Co., Ltd. at 1 site 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 8 inclusion and 20 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: status not confirmed, as of the sponsor's last update on 14 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 1 site 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sujiang Zhang, M.D. (+86-17717285030, zbruce.zhang@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Red blood cell (RBCs) transfusion requirements, whether reaching TI (time frame: 24 months). The study lists 2 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 14 Jun 2024.