- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05015920
A Study Evaluating the Safety and Efficacy of the BD211 Drug Product in β-Thalassemia Major Participants
A Phase 1 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy in Subjects With β-Thalassemia Major by Transplantation of Autologous CD34+Stem Cells Transduced With a Lentiviral Vector Encoding βA-T87Q-Globin
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
After collection of mobilised peripheral blood samples, the patient's autologous cells,enriched for CD34+ HSCs, undergo ex vivo transduction with lentiviral vector encoding βA-T87Q-globin to BD211 finished product,which is then infused intravenously into the patient after myeloablative busulfan conditioning to prepare bone marrow "niches" for engraftment of the HSCs.
After discharge, subjects will be followed monthly, at a minimum, for 6 months and thereafter every 3 months for the remainder of the 24 months post-transplant.
Evaluation will include Routine and special biological testing at regular intervals, collection of AEs and concomitant medications, and evaluation of disease specific biological and clinical parameters.
Subjects will then be enrolled in a long-term follow-up protocol with annual evaluations for an additional 13 years post-transplant.
The long-term follow-up study will focus on long-term safety, with an emphasis on integration site analysis, and long-term efficacy.
This study will end when the last subject completes the Month 24 visit or discontinues from the study.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Sanbin Wang, Dr.
- Phone Number: +86-871-2637866
- Email: sanbin1011@163.com
Study Locations
-
-
Yunnan
-
Kunming, Yunnan, China, 650000
- Recruiting
- 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
-
Contact:
- Sanbing Wang, Dr.
- Phone Number: 13187424131
- Email: sanbin1011@163.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
1.5 to 35 years of age.
2.Be eligible for allogeneic HSCT based on institutional medical guideline, but without a matched related donor.
3.Transfusion-dependent β-Thalassemia Major, regardless of the genotype, with the diagnosis confirmed by Hb studies. Subjects must be stable and maintained on an appropriate iron chelation regimen. Transfusion dependence is defined as requiring at least 100 mL/kg/year of packed red blood cells(pRBCs).
4.Have been treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.
5.Be willing and able, in the Investigator's opinion, to comply with the study procedures outlined in the study protocol. If a pediatric subject, the subject's parent/legal guardian also must be willing and able to comply with the study procedures outlined in the study protocol.
Exclusion Criteria:
- Availability of a willing matched HLA-identical sibling hematopoietic cell donor.
- Positive for presence of human immunodeficiency virus, human T-lymphotropic virus, vesicular stomatitis virus G antibody.
- Clinically significant, active bacterial, viral, fungal, or parasitic infection.
- A white blood cell (WBC) count<3x109/L and/or platelet count<120x109/L
- Receipt of an allogeneic transplant.
- Receipt of erythropoietin within 3 months before HSCT harvest.
- Contraindication to anesthesia for bone marrow harvesting.
- Any of prior or current malignancy, myeloproliferative or immunodeficiency disorder.
- Active relapsing malaria
- Immediate family member with a known or suspected Familial Cancer Syndrome.
- Diagnosis of significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study.
- Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects.
- Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician.
- History of major organ damage.including Liver, Heart, Kidney disease, pulmonary hypertension ,severe iron overload, which in the opinion of the physician is grounds for exclusion.
- Participation in another clinical study with an investigational drug within 30 days of screening.
- Hydroxyurea therapy within 3 months before hematopoietic stem cell collection.
- An assessment by the Investigator that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.
- Subjects who have the desire to become a parent within the 27-month study period.
- Prior receipt of gene therapy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Mobilization,harvest,transduction,conditioning,treatment,engraftment
Subjects will participate in this study for a total of approximately 27 months, consisting of an up to 3 months pre-transplant period(consisting of a screening period followed by autologous cell harvest, followed by a waiting period during which the harvested cells are transduced and undergo release testing, followed by treatment with busulfan IV, and a single infusion of BD211 Drug Product) and a 24-month post-transplant evaluation period.
Following completion of this study, all subjects will be asked to provided consent to participate in a follow-up study for another 13 years, which will focus on long-term safety, with an emphasis on integration site analysis, and long-term efficacy.
|
Transplantation of Autologous CD34+Stem Cells Transduced to BD211 finished Product with a Lentiviral Vector coding βA-T87Q-Globin.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluate the success and kinetics of HSC engraftment.
Time Frame: At multiple timepoints after infusion for 24 months.
|
Three consecutive absolute neutrophil counts≥500 cells/uL, three consecutive platelet values ≥20 e9/L, measure blood samples monthly after BD211 drug product infusion.
|
At multiple timepoints after infusion for 24 months.
|
Incidence of transplant-related mortality through 100 days post-transplant.
Time Frame: Up to 100 days post-HSCT.
|
Up to 100 days post-HSCT.
|
|
Overall survival of maintenance phase.
Time Frame: Up to 24 months post-HSCT.
|
Up to 24 months post-HSCT.
|
|
Post-transplant blood samples for replication competent lentivirus (RCL) testing.
Time Frame: At multiple timepoints after infusion for 24 months.
|
The testing of any subject positivity will be considered an SAE and suspend the inclusion of new subjects.
|
At multiple timepoints after infusion for 24 months.
|
Assessment of Clonal dominance or leukemia/lymphoma and other malignancies.
Time Frame: At multiple timepoints after infusion for 24 months.
|
Using peripheral blood of subjects for integration site analysis via LAM-PCR & deep sequencing.
|
At multiple timepoints after infusion for 24 months.
|
Incidence of treatment- related adverse events.
Time Frame: Up to 24 months after BD211 drug product infusion.
|
According to the requirements of the National Cancer Institute Common Terminology Standards for Adverse Events (NCI CTCAE) version 5.0, monitor laboratory parameters and the frequency and severity of clinical AEs.
|
Up to 24 months after BD211 drug product infusion.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quantify gene transfer efficiency and expression of BD211 drug product.
Time Frame: Up to 24 months after engraftment.
|
Expression of βA-T87Q-globin chain in whole blood by assessing the ratio of βA-T87Q-globin to α-globin, as well as βA-T87Q-globin fractions in all β-chains over time by HPLC.
|
Up to 24 months after engraftment.
|
Quantify the hematopoietic chimerism resulting from treatment with BD211 drug product.
Time Frame: Up to 24 months after engraftment.
|
Measuring lentiviral vector copy number per diploid genome(c/dg) for evaluation.
|
Up to 24 months after engraftment.
|
Measure the effects of transplantation with BD211 on the expression of disease-specific biological parameters and clinical events, including amounts of HbAT87Q in peripheral blood in grams per deciliter (g/dL).
Time Frame: Up to 24 months after engraftment.
|
Up to 24 months after engraftment.
|
|
Reduction from baseline of RBC transfusion requirements (mL/kg) per month and year post-transplant.
Time Frame: Up to 24 months after engraftment.
|
Up to 24 months after engraftment.
|
|
Duration of transfusion independence (months).
Time Frame: Up to 24 months after engraftment.
|
Up to 24 months after engraftment.
|
|
Weighted average Hemoglobin during transfusion independence in grams per deciliter (g/dL).
Time Frame: Up to 24 months after engraftment.
|
Up to 24 months after engraftment.
|
|
Changes from baseline in iron burden by assessing liver iron content (mg Fe/g dry weight).
Time Frame: Up to 24 months after engraftment.
|
Up to 24 months after engraftment.
|
|
Changes from baseline in iron burden by assessing cardiac iron content using magnetic resonance imaging (MRI) T2* value (milliseconds, ms).
Time Frame: Up to 24 months after engraftment.
|
Up to 24 months after engraftment.
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Sanbin Wang, Dr., 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 920IEC/AF/61/2019-01.0
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
Clinical Trials on Hematologic Diseases
-
St. Jude Children's Research HospitalRecruitingRefractory Hematologic Malignancy | Relapsed Hematologic MalignancyUnited States
-
Epizyme, Inc.WithdrawnRefractory Hematologic Malignancy | Relapsed Hematologic MalignancyUnited States
-
University of Colorado, DenverNot yet recruitingHematologic Malignancy | Pediatric Patients | Other Hematologic ConditionUnited States
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.Not yet recruitingHematologic MalignancyChina
-
Innovent Biologics (Suzhou) Co. Ltd.Recruiting
-
Massachusetts General HospitalRecruiting
-
Fondazione EMN Italy OnlusCompletedHEMATOLOGIC MALIGNANCIESItaly
-
Center for International Blood and Marrow Transplant...National Cancer Institute (NCI); National Heart, Lung, and Blood Institute... and other collaboratorsCompletedHematologic MalignancyUnited States
-
Rigshospitalet, DenmarkNovo Nordisk A/SCompletedHematologic MalignancyDenmark
-
SecuraBioCompletedHematologic MalignancyUnited States, Italy
Clinical Trials on BD211 Drug Product
-
Shanghai BDgene Co., Ltd.Shanghai Children's Medical CenterNot yet recruiting
-
Shanghai BDgene Co., Ltd.Ruijin HospitalNot yet recruiting
-
Assistance Publique - Hôpitaux de ParisActive, not recruiting
-
Assistance Publique - Hôpitaux de ParisRecruitingArtemis (DCLRE1C ) Deficient Severe Combined ImmunodeficiencyFrance
-
Lumosa Therapeutics Co., Ltd.UnknownAcute Ischemic StrokeTaiwan, United States
-
Capstone TherapeuticsCompletedScar Prevention | Scar ReductionUnited States
-
First Affiliated Hospital of Guangxi Medical UniversityGenmedicn Biopharma Ltd.RecruitingTransfusion-dependent α-ThalassemiaChina
-
Kamau TherapeuticsRecruitingSickle Cell DiseaseUnited States
-
Regenera Pharma LtdWithdrawnPartial Thickness Burn | Second Degree Burn Less Than 5%TBSAIsrael