SNPMiner Trials (Home Page)
Report for Mutation T87Q
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 5 clinical trials
Clinical Trials
1 A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy in Subjects With β-Thalassemia Major by Transplantation of Autologous CD34+ Cells Transduced Ex Vivo With a Lentiviral βA-T87Q-Globin Vector (LentiGlobin® BB305 Drug Product)
This is a non-randomized, open label, multi-site, single-dose, phase 1/2 study in up to 18 participants (including at least 3 adolescents between 12 and 17 years of age, inclusive) with β-thalassemia major. The study will evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product [autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human βA-T87Q-globin gene].
NCT01745120 β-thalassemia Major Genetic: LentiGlobin BB305 Drug Product MeSH:Thalassemia beta-Thalassemia
A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy in Subjects With β-Thalassemia Major by Transplantation of Autologous CD34+ Cells Transduced Ex Vivo With a Lentiviral βA-T87Q-Globin Vector (LentiGlobin® BB305 Drug Product). --- T87Q ---
The study will evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product [autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human βA-T87Q-globin gene]. --- T87Q ---
Percentage of Participants With Sustained Production of >=2.0 Grams Per Deciliter (g/dL) of Hemoglobin A (HbA) Containing βA-T87Q-globin (HbAT87Q) for the Six Months Between Month 18 and Month 24. --- T87Q ---
Percentage of participants with sustained production of >=2.0 grams per deciliter (g/dL) of hemoglobin A (HbA) containing βA-T87Q-globin (HbAT87Q) for 6 months (Month 18 to Month 24) was reported.. Percentage of Participants Who Achieved Transfusion Independence (TI). --- T87Q ---
Primary Outcomes
Description: Percentage of participants with sustained production of >=2.0 grams per deciliter (g/dL) of hemoglobin A (HbA) containing βA-T87Q-globin (HbAT87Q) for 6 months (Month 18 to Month 24) was reported.
Measure: Percentage of Participants With Sustained Production of >=2.0 Grams Per Deciliter (g/dL) of Hemoglobin A (HbA) Containing βA-T87Q-globin (HbAT87Q) for the Six Months Between Month 18 and Month 24 Time: Month 18 to Month 24Description: TI was defined as a weighted average hemoglobin (Hb) >= 9 g/dL without any packed red blood cells (pRBC) transfusions for a continuous period of >=12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Percentage of participants who achieved TI from time of drug product infusion up to 24 months was reported.
Measure: Percentage of Participants Who Achieved Transfusion Independence (TI) Time: From time of drug product infusion up to 24 monthsSecondary Outcomes
Description: TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion.
Measure: Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24 Time: Month 18, Month 24Description: TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Time period of TI will start when participants achieve a Hb >= 9 g/dL with no transfusions in the preceding 60 days. Duration of TI was calculated as the time from the start of TI (i.e. first Hb >= 9 g/dL with no transfusions in the preceding 60 days) up to the last available Hb at which the TI criteria are still met.
Measure: Duration of Transfusion Independence (TI) Time: From time of drug product infusion up to 24 monthsDescription: TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Time From LentiGlobin BB305 Drug Product Infusion to last pRBC transfusion prior to achieving TI was reported.
Measure: Time From LentiGlobin BB305 Drug Product Infusion to Last pRBC Transfusion Prior to Achieving Transfusion Independence (TI) Time: From time of drug product infusion up to 24 monthsDescription: TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Time from drug product infusion to initial achievement of TI was calculated as the time from drug product infusion to the first Hb at which a participant can be declared as TI.
Measure: Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI) Time: From time of drug product infusion up to 24 monthsDescription: The weighted average Hb is an average area under the curve during the period of TI, from the start of TI when the Hb is first >= 9 g/dL with no transfusions in the preceding 60 days to the last available Hb at which the TI criteria are still met. TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Weighted average Hb during the period of TI was reported.
Measure: Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) Time: From time of drug product infusion up to 24 monthsDescription: The annualized number of pRBC transfusions over the 2 year period prior to drug product infusion was compared to the annualized number of pRBC transfusions during the Month 6 to Month 24 period post drug product infusion and the percentage change was reported.
Measure: Percentage Change From Baseline in Annualized Number of Packed Red Blood Cells (pRBC) Transfusions at Month 24 Time: Baseline, Month 24Description: The annualized volume of pRBC transfusions over the 2 year period prior to drug product infusion was compared to the annualized volume of pRBC transfusions in the Month 6 to Month 24 period post drug product Infusion and the percentage change from baseline was reported.
Measure: Percentage Change From Baseline in Average Annual Packed Red Blood Cells (pRBC) Transfusion Volume at Month 24 Time: Baseline, Month 24Description: Weighted average Hb nadir was defined as an average area under the curve where the Hb closest but within 3 days prior to a transfusion is used as the Hb nadir. If there is a period of more than 60 days without a pRBC transfusion, all Hb records between Day 61 and day of last visit or next transfusion (inclusive) were also considered as nadirs. The weighted average nadir Hb during the period of Month 6 to Month 24 was compared to the weighted average nadir Hb during the 2 years prior to enrollment.
Measure: Weighted Average Nadir Hemoglobin (Hb) Time: Baseline, Month 6 to Month 24Description: Neutrophil engraftment was defined as achieving 3 consecutive absolute neutrophil count (ANC) >= 0.5 × 10^9/L on different days after a post-transplant value of < 0.5 × 10^9/L within 42 days after drug product infusion.
Measure: Number of Participants With Successful Neutrophil Engraftment Time: From time of drug product infusion up to 24 monthsDescription: Time to neutrophil engraftment was defined as the time to the first of 3 consecutive absolute neutrophil count (ANC) >= 0.5 × 10^9/L obtained on different days after a post-transplant value of < 0.5 × 10^9/L. The Day of neutrophil engraftment is the first day of the 3 consecutive measurements, where Day 1 is the day of drug product infusion.
Measure: Time to Neutrophil Engraftment Time: From time of drug product infusion up to 24 monthsDescription: Platelet engraftment was defined as achieving 3 consecutive platelet values >= 20 × 10^9/L on different days after a post-transplant value of < 20 × 10^9/L, while no platelet transfusions administered for 7 days immediately preceding and during the evaluation period.
Measure: Number of Participants With Successful Platelet Engraftment Time: From time of drug product infusion up to 24 monthsDescription: Time to platelet engraftment was defined as achieving of first 3 consecutive platelet values >= 20 × 10^9/L obtained on different days after a post-transplant value of < 20 × 10^9/L, while no platelet transfusions administered for 7 days immediately preceding and during the evaluation period. The day of platelet engraftment is the first day of the 3 consecutive measurements, where Day 1 is the day of drug product infusion.
Measure: Time to Platelet Engraftment Time: From time of drug product infusion up to 24 monthsDescription: Transplant-related mortality was determined by the investigator (any deaths considered related to the transplant.)
Measure: Transplant-related Mortality Time: Through 100 and 365 days post-LentiGlobin BB305 Drug Product infusionDescription: Overall survival was defined as time from date of LentiGlobin BB305 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. Percentage of participants who survived throughout the study were reported.
Measure: Overall Survival Time: From time of drug product infusion up to 24 monthsDescription: Blood samples were analyzed for detection of RCL using RCL co-culture assay.
Measure: Percentage of Participants Detected With Replication-competent Lentivirus (RCL) Time: From time of drug product infusion up to 24 monthsDescription: Linear amplification-mediated polymerase chain reaction (LAM-PCR) coupled with next generation sequencing and subsequent (semi-) automated data mining allowed high-throughput analysis of vector integration site (IS) in blood cells from treated participants at multiple time points. ISs detected in peripheral blood cells at early time points generally were due to the expansion of transduced short-term progenitor stem cell clones, and gradually shift to include sites detected due to expansion of transduced long-term stem cell clones. An efficient transduction procedure was anticipated to give rise to a polyclonal population in the participant, reflected by the detection of multiple IS. Additionally, ISA allowed monitoring of the relative contribution of individual clones over time. Number of participants who had IS that contributed to >=30% of the total clones at any time was used as a first step to investigating whether clonal dominance was achieved.
Measure: Number of Participants With Integration Site Analysis (ISA) With >30% Clonal Contribution Time: From time of drug product infusion up to 24 monthsDescription: An AE was defined as any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was any AE, occurring at any dose and regardless of causality that: results in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect.
Measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Time: From signing of informed consent to 24 months after the drug product infusion2 A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy of the β-Hemoglobinopathies (Sickle Cell Anemia and β-Thalassemia Major) by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral β-A-T87Q Globin Vector (LentiGlobin BB305 Drug Product)
This is a Phase 1/2, open label, safety, and efficacy study of the administration of LentiGlobin BB305 Drug Product to participants with either transfusion dependent beta-thalassemia (TDT) or sickle cell disease (SCD).
NCT02151526 Beta-Thalassemia Major Sickle Cell Disease Drug: LentiGlobin BB305 Drug Product MeSH:Anemia, Sickle Cell Thalassemia beta-Thalassemia
A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy of the β-Hemoglobinopathies (Sickle Cell Anemia and β-Thalassemia Major) by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral β-A-T87Q Globin Vector (LentiGlobin BB305 Drug Product). --- T87Q ---
Number of VOCs, ACS, and vaso-occlusive events (VOEs; which included both VOC and ACS) through 24 months after drug product infusion.. Therapeutic Globin Expression Measured by Hb Containing β^A -T87Q Globin (HbA^T87Q) in Peripheral Blood. --- T87Q ---
The relative amount of each globin produced by a participant (including βA^A-T87Q globin) was determined in peripheral blood throughout the study.. Vector Copy Number (VCN) in Peripheral Blood. --- T87Q ---
Primary Outcomes
Description: Neutrophil engraftment was defined as the first of absolute neutrophil count (ANC) > or = 0.5 × 10^9/ liter (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 with TDT and values > or =50 × 10^9/L for participants with SCD obtained on different days with no platelet transfusions administered for 7 days immediately preceding and during the evaluation period. The day of engraftment is the first day of the 3 consecutive platelet measurements.
Measure: Number of Treated Participants With Successful Neutrophil and Platelet Engraftment Time: From time of drug product infusion through Month 24Description: Neutrophil engraftment was defined as the first of ANC > or = 0.5 × 10^9/ liter (L) for 3 consecutive days (or 3 consecutive measurements done on separate days), after a post-transplant value < 0.5 × 10^9/L). Platelet engraftment was defined as the first of 3 consecutive platelet values > or =20 × 10^9/L for participants with TDT and values > or =50 × 10^9/L for participants with SCD obtained on different days with no platelet transfusions administered for 7 days immediately preceding and during the evaluation period. The day of engraftment is the first day of the 3 consecutive platelet measurements.
Measure: Time to Successful Neutrophil and Platelet Engraftment Time: From time of drug product infusion through Month 24Description: This was the safety outcome measure related to mortality. Transplant related mortality was defined as any death occurring in the study post drug product infusion deemed related to the transplant by the investigator.
Measure: Incidence of Transplant Related Mortality Time: From screening through 365 days post-transplantDescription: Overall survival was defined as time from date of LentiGlobin BB305 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. Number of participants with OS events were reported.
Measure: Number of Participants With Overall Survival (OS) Events Time: From time of drug product infusion through Month 24Description: Blood samples were analyzed for detection of RCL using RCL co-culture assay.
Measure: Percentage of Participants With Vector-Derived Replication-Competent Lentivirus (RCL) Time: From time of drug product infusion through Month 24Description: Clonal dominance was defined as an ISA result greater than (>) 90% of the total insertion sites (IS) at any time and a vector copy number (VCN) > or =0.3, or an initial ISA result of > 30% of the total IS with a VCN > or =0.3 followed by a result > 30% and less than or equal to (< or =) 90% at first repeat and a result > 50% at second repeat.
Measure: Number of Treated Participants With Greater Than (>) 30 Percent (%) Contribution of an Individual Clone As Per Integration Site Analysis (ISA) Time: From time of drug product infusion through Month 24Description: 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. This definition includes inter-current illnesses or injuries, and exacerbation of pre-existing conditions. An SAE was any AE, occurring at any dose and regardless of causality, that resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or was considered an important medical event that may jeopardize the participant and may require medical or surgical intervention to prevent an outcome listed previously. The number of participants with AEs and SAEs were evaluated.
Measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Time: From date of Informed Consent signing up to Month 24Secondary Outcomes
Description: TI was defined as a weighted average hemoglobin (Hb) > or =9 grams per deciliter (g/dL) without any pRBC transfusions for a continuous period of > or =12 months at any time during the study after drug product infusion, where calculation of time period of TI starts when participants achieve a Hb > or =9 g/dL with no transfusions in the preceding 60 days.
Measure: Percentage of Treated Participants With Transfusion-Dependent β-Thalassemia (TDT) Who Achieved Transfusion Independence (TI) Time: From time of drug product infusion through Month 24Description: TI was defined as a weighted average hemoglobin (Hb) > or =9 grams per deciliter (g/dL) without any pRBC transfusions for a continuous period of > or =12 months at any time during the study after drug product infusion, where calculation of time period of TI starts when participants achieve a Hb > or =9 g/dL with no transfusions in the preceding 60 days.
Measure: Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT) Time: From time of drug product infusion through Month 24Description: TI was defined as a weighted average Hb > or =9 grams per deciliter (g/dL) without any pRBC transfusions for a continuous period of > or =12 months at any time during the study after drug product infusion, where calculation of time period of TI starts when participants achieve a Hb > or =9 g/dL with no transfusions in the preceding 60 days. To meet the initial TI criteria, the weighted Hb must be > or =9 g/dL at the end of the 12-month period, to remain in the TI state beyond the 12-month period, the treated participant needs to maintain a weighted Hb of > or =9 g/dL from that point forward, without receiving a pRBC transfusion. This outcome measure reports the duration of TI and was evaluated in the TDT Transplant Population (TP) that reached TI.
Measure: Duration of Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT) Time: From time of drug product infusion through Month 24Description: TI was defined as a weighted average Hb > or =9 grams per deciliter (g/dL) without any pRBC transfusions for a continuous period of > or =12 months at any time during the study after drug product infusion, where calculation of time period of TI starts when participants achieve a Hb > or =9 g/dL with no transfusions in the preceding 60 days. To meet the initial TI criteria, the weighted Hb must be > or =9 g/dL at the end of the 12-month period, to remain in the TI state beyond the 12-month period, the treated participant needs to maintain a weighted Hb of > or =9 g/dL from that point forward, without receiving a pRBC transfusion. This endpoint reports the time from infusion to the last pRBC transfusion prior to achieving TI.
Measure: Time From LentiGlobin BB305 Drug Product Infusion to Last Packed Red Blood Cells (pRBC) Transfusion Prior to Achieving Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT) Time: From time of drug product infusion through Month 24Description: TI was defined as a weighted average Hb > or =9 grams per deciliter (g/dL) without any pRBC transfusions for a continuous period of > or =12 months at any time during the study after drug product infusion, where calculation of time period of TI starts when participants achieve a Hb > or =9 g/dL with no transfusions in the preceding 60 days. To meet the initial TI criteria, the weighted Hb must be > or =9 g/dL at the end of the 12-month period, to remain in the TI state beyond the 12-month period, the treated participant needs to maintain a weighted Hb of > or =9 g/dL from that point forward, without receiving a pRBC transfusion. This outcome measure reports the time from infusion to achievement of TI.
Measure: Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT) Time: From time of drug product infusion through Month 24Description: Weighted average Hb nadir was defined as an average area under the curve where the Hb closest but within 3 days prior to a transfusion was used as the Hb nadir. Hb values on the day of the transfusion were considered for nadir calculations.
Measure: Weighted Average Nadir Hemoglobin (Hb) in Participants With Transfusion-Dependent β-Thalassemia (TDT) Time: From 6 months post-drug product infusion through Month 24Description: Percent change from baseline in the average annual transfusion volume from 6 months post-drug product infusion through last visit were reported.
Measure: Percentage Change From Baseline in Annualized Packed Red Blood Cell (pRBC) Transfusion Volume Time: Baseline, From 6 months post-drug product infusion through Month 24Description: Percentage change from baseline in annualized number of pRBC transfusions from 6 months post-drug product infusion through last visit were reported.
Measure: Percentage Change From Baseline in Annualized Number of Packed Red Blood Cell (pRBC) Transfusions Time: Baseline, From 6 months post-drug product infusion through Month 24Description: Number of VOCs, ACS, and vaso-occlusive events (VOEs; which included both VOC and ACS) through 24 months after drug product infusion.
Measure: Number of Participants With Vaso-Occlusive Crisis (VOC) and/or Acute Chest Syndrome (ACS) Events Post Drug Product Infusion in Sickle Cell Disease Participants Time: From time of drug product infusion through Month 24Description: Therapeutic globin expression was measured by HbA^T87Q in peripheral blood and the ratio of alpha(α)- globin to all beta (β)-like-globins. The relative amount of each globin produced by a participant (including βA^A-T87Q globin) was determined in peripheral blood throughout the study.
Measure: Therapeutic Globin Expression Measured by Hb Containing β^A -T87Q Globin (HbA^T87Q) in Peripheral Blood Time: From time of drug product infusion through Month 24Description: LentiGlobin BB305 lentiviral vector (LVV) transduction efficiency was measured by VCN. The presence of vector sequences in the genomic DNA of cells is detected using quantitative polymerase chain reaction (qPCR), and results were expressed as VCN.
Measure: Vector Copy Number (VCN) in Peripheral Blood Time: From time of drug product infusion through Month 243 Longterm Follow-up of Subjects With Hemoglobinopathies Treated With Ex Vivo Gene Therapy Using Autologous Hematopoietic Stem Cells Transduced With a Lentiviral Vector
This is a multi-center, long-term safety and efficacy follow-up study for subjects with hemoglobinopathies (β-thalassemia or severe sickle cell disease) who have been treated with ex vivo gene therapy drug product in bluebird bio-sponsored clinical studies. After completing the parent clinical study (approximately 2 years), eligible subjects will be followed for an additional 13 years for a total of 15 years post-drug product infusion. No investigational drug product will be administered in the study.
NCT02633943 Beta-Thalassemia Sickle Cell Disease Other: Safety and efficacy assessments MeSH:Anemia, Sickle Anemia, Sickle Cell Thalassemia beta-Thalassemia Hemoglobinopathies
Monitoring of βA-T87Q-globin. --- T87Q ---
Primary Outcomes
Measure: Overall survival of subjects with hemoglobinopathies treated with gene therapy drug product in a bluebird bio-sponsored clinical study Time: 15 years post-drug product infusionMeasure: All adverse events (AEs) related to drug product Time: 15 years post-drug product infusion
Measure: All serious adverse events (SAEs) Time: 15 years post-drug product infusion
Measure: Monitoring for persistence of vector sequences by polymerase chain reaction to determine vector copy number (VCN) Time: 15 years post-drug product infusion
Measure: Monitoring of βA-T87Q-globin Time: 15 years post-drug product infusion
Measure: Assessment of transfusions required (mL of packed red blood cells/kg/year) in subjects with β-thalassemia Time: 15 years post-drug product infusion
Measure: Assessment of iron content in the liver and heart by cardiac magnetic resonance imaging (MRI) and blood draws in subjects with β-thalassemia Time: 15 years post-drug product infusion
Measure: Frequency of AEs from subjects with severe sickle cell disease including acute chest syndrome (ACS), severe vaso-occlusive episodes (VOC), and stroke or ischemic attacks Time: 15 years post-drug product infusion
4 A Phase 3 Single Arm Study Evaluating the Efficacy and Safety of Gene Therapy in Subjects With Transfusion-dependent β-Thalassemia, Who do Not Have a β0/β0 Genotype, by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral βA-T87Q-Globin Vector in Subjects ≤50 Years of Age
This is a single-arm, multi-site, single-dose, Phase 3 study in approximately 23 subjects ≤50 years of age with transfusion-dependent β-thalassemia (TDT), also known as β-thalassemia major, who do not have a β0 mutation at both alleles of the hemoglobin β (HBB) gene. The study will evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product.
NCT02906202 Beta-Thalassemia Genetic: LentiGlobin BB305 Drug Product MeSH:Thalassemia beta-Thalassemia
A Phase 3 Single Arm Study Evaluating the Efficacy and Safety of Gene Therapy in Subjects With Transfusion-dependent β-Thalassemia, Who do Not Have a β0/β0 Genotype, by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral βA-T87Q-Globin Vector in Subjects ≤50 Years of Age. --- T87Q ---
Primary Outcomes
Description: TI is defined as a weighted average Hb ≥9g/dL without any RBC transfusions for a continuous period of ≥12 months at any time during the study after drug product infusion.
Measure: The proportion of treated subjects who meet the definition of "transfusion independence" (TI). Time: 12 - 24 months post-transplantSecondary Outcomes
Measure: Engraftment defined as an absolute neutrophil count ≥500 cells/µL for 3 consecutive days Time: 24 months post-transplantMeasure: Detection of vector-derived replication competent lentivirus (RCL) using a RCL screening assay Time: 24 months post-transplant
Measure: Frequency of events of insertional mutagenesis leading to clonal dominance or leukemia Time: 24 months post-transplant
Measure: Frequency of clinical adverse events Time: 24 months post-transplant
Measure: Percentage of subjects with a reduction in the mL/kg RBC transfused from Month 12 through Month 24 after drug product infusion of at least 50% compared to the average annual RBC transfusion requirement during the 2 years prior to enrollment. Time: 24 months post-transplant
5 A Phase 3 Single Arm Study Evaluating the Efficacy and Safety of Gene Therapy in Subjects With Transfusion-dependent β-Thalassemia by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral βA-T87Q-Globin Vector in Subjects ≤50 Years of Age
This is a single-arm, multi-site, single-dose, Phase 3 study in approximately 18 subjects ≤50 years of age with transfusion-dependent β-thalassemia (TDT), who have a β0/β0, β0/IVS-I-110, or IVS-I-110/IVS-I-110 genotype. The study will evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product.
NCT03207009 Beta-Thalassemia Genetic: LentiGlobin BB305 Drug Product MeSH:Thalassemia beta-Thalassemia
A Phase 3 Single Arm Study Evaluating the Efficacy and Safety of Gene Therapy in Subjects With Transfusion-dependent β-Thalassemia by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral βA-T87Q-Globin Vector in Subjects ≤50 Years of Age. --- T87Q ---
Primary Outcomes
Description: TR is defined as demonstration of reduction in volume of RBC transfusion requirements (in mL/kg) in the post-treatment time period of Months 12 to 24 compared to the average annual transfusion requirement in the 24 months prior to enrollment.
Measure: The proportion of subjects who meet the definition of "transfusion reduction" (TR). Time: 12-24 months post-transplantSecondary Outcomes
Measure: The proportion of treated subjects who meet the definition of "transfusion independence" (TI). TI is defined as Hb ≥9g/dL without any RBC transfusions for a continuous period of ≥12 months at any time during the study after drug product infusion. Time: 12-24 months post-transplantMeasure: Percentage of subjects with a reduction in the mL/kg RBC transfused from Month 12 through Month 24 after drug product infusion of at least 50% compared to the average annual RBC transfusion requirement during the 2 years prior to enrollment. Time: 12-24 months post-transplant
Measure: Engraftment defined as an absolute neutrophil count ≥500 cells/µL for 3 consecutive days Time: 24 months post-transplant
Measure: Detection of vector-derived replication competent lentivirus (RCL) using a RCL screening assay Time: 24 months post-transplant
Measure: Frequency of events of insertional mutagenesis leading to clonal dominance or leukemia. Time: 24 months post-transplant
Measure: Frequency of clinical adverse events Time: 24 months post-transplant