SNPMiner Trials by Shray Alag


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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 24

Description: 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 months

Secondary 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 24

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. 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 months

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. 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 months

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. 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 months

Description: 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 months

Description: 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 24

Description: 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 24

Description: 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 24

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 infusion

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 infusion

2 A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy of the Beta-Hemoglobinopathies (Sickle Cell Disease and Beta-Thalassemia Major) by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral Beta-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 subjects with either beta-thalassemia major or severe sickle cell disease (SCD).

NCT02151526 Beta-Thalassemia Major Sickle Cell Disease Genetic: 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 Beta-Hemoglobinopathies (Sickle Cell Disease and Beta-Thalassemia Major) by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral Beta-A-T87Q Globin Vector (LentiGlobin BB305 Drug Product). --- T87Q ---

Therapeutic globin expression, as measured by assessing the ratio of beta A-T87Q-globin to alpha-globin in whole blood, as well as the amount of beta A-T87Q-globin as a fraction of all beta-chains in whole blood. --- T87Q ---

Therapeutic globin expression, as measured by assessing the ratio of beta A-T87Q-globin to alpha-globin in whole blood, as well as the amount of beta A-T87Q-globin as a fraction of all beta-chains in whole blood. --- T87Q --- --- T87Q ---

Primary Outcomes

Measure: Success and kinetics of hematopoietic stem cell (HSC) engraftment

Time: 1-24 months post-transplant

Measure: Incidence of transplant related mortality through 100 days post treatment

Time: 1-24 months post-transplant

Measure: Overall survival

Time: 1-24 months post-transplant

Measure: Detection of vector derived replication-competent lentivirus (RCL) in any subject

Time: 1-24 months post-transplant

Measure: Characterization of events of insertional mutagenesis leading to clonal dominance or leukemia

Time: 1-24 months post-transplant

Description: AEs assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.

Measure: Monitoring of laboratory parameters and frequency and severity of clinical AEs

Time: 1-24 months post-transplant

Secondary Outcomes

Description: Therapeutic globin expression, as measured by assessing the ratio of beta A-T87Q-globin to alpha-globin in whole blood, as well as the amount of beta A-T87Q-globin as a fraction of all beta-chains in whole blood

Measure: Quantify gene transfer efficiency and expression by evaluation

Time: 1-24 months post-transplant

Description: Average vector copy number (VCN) in cell populations from peripheral blood and bone marrow containing the integrated LentiGlobin BB305 lentiviral vector.

Measure: Quantify gene transfer efficiency and expression by evaluation

Time: 1-24 months post-transplant

Description: For all subjects, red blood cell (RBC) transfusion requirements (measured in milliliters [mL] per kilogram [kg]) per month and per year post transplant

Measure: Efficacy

Time: 1-24 months post-transplant

Description: For sickle cell disease (SCD) subjects only, vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) events in each subject compared with the 2 year pre-treatment period

Measure: Efficacy

Time: 1-24 months post-transplant

3 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 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 infusion

Measure: 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-transplant

Secondary Outcomes

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

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-transplant

Secondary 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-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: 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


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