β-thalassemia Major
Conditions
Keywords
gene therapy, β thalassemia, hemoglobin, anemia, CD34
Brief summary
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 \[autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human βA-T87Q-globin gene\].
Detailed description
Subject participation for this study will be 2 years. Subjects who enroll in this study will be asked to participate in a subsequent long-term follow up study that will monitor the safety and efficacy of the treatment they receive for up to 13 years post-transplant.
Interventions
Transplant of autologous hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector.
Sponsors
Genetix Biotherapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Participants between 12 and 35 years of age, inclusive, at the time of consent/assent, and able to provide written consent/assent, if applicable. * Diagnosis of β-thalassemia major and a history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year for the prior 2 years. * Eligible for allogeneic bone marrow transplant. * Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.
Exclusion criteria
* Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1 and HIV 2). * A white blood cell (WBC) count \<3 × 10\^9/L, and / or platelet count \<100 × 10\^9/L if not due to hypersplenism. * Uncorrected bleeding disorder. * Any prior or current malignancy or myeloproliferative or immunodeficiency disorder. * Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome and familial adenomatous polyposis). * Receipt of an allogeneic transplant. * Advanced liver disease, including persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value \>3 × the upper limit of normal, liver biopsy demonstrating cirrhosis, extensive bridging fibrosis, or active hepatitis. * Kidney disease with a calculated creatinine clearance \<30% normal value. * Uncontrolled seizure disorder. * Diffusion capacity of carbon monoxide (DLco) \<50% of predicted (corrected for hemoglobin). * A cardiac T2\* \<10 ms by magnetic resonance imaging (MRI). * Any other evidence of severe iron overload that, in the Investigator's opinion, warrants exclusion. * Clinically significant pulmonary hypertension, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental home oxygen. * Participation in another clinical study with an investigational drug within 30 days of Screening. * Any prior or current malignancy or myeloproliferative disorder. * Prior receipt of gene therapy.
Design outcomes
Primary
| Measure | Time frame | 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 the Six Months Between Month 18 and Month 24 | Month 18 to Month 24 | 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) | From time of drug product infusion up to 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From LentiGlobin BB305 Drug Product Infusion to Last pRBC Transfusion Prior to Achieving Transfusion Independence (TI) | From time of drug product infusion up to 24 months | 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. |
| Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI) | From time of drug product infusion up to 24 months | 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. |
| Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) | From time of drug product infusion up to 24 months | 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. |
| Percentage Change From Baseline in Annualized Number of Packed Red Blood Cells (pRBC) Transfusions at Month 24 | Baseline, Month 24 | 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. |
| Weighted Average Nadir Hemoglobin (Hb) | Baseline, Month 6 to Month 24 | 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. |
| Percentage of Participants Detected With Replication-competent Lentivirus (RCL) | From time of drug product infusion up to 24 months | Blood samples were analyzed for detection of RCL using RCL co-culture assay. |
| Percentage Change From Baseline in Average Annual Packed Red Blood Cells (pRBC) Transfusion Volume at Month 24 | Baseline, Month 24 | 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. |
| Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24 | Month 18, Month 24 | 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 to Neutrophil Engraftment | From time of drug product infusion up to 24 months | 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. |
| Number of Participants With Successful Platelet Engraftment | From time of drug product infusion up to 24 months | 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. |
| Time to Platelet Engraftment | From time of drug product infusion up to 24 months | 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. |
| Transplant-related Mortality | Through 100 and 365 days post-LentiGlobin BB305 Drug Product infusion | Transplant-related mortality was determined by the investigator (any deaths considered related to the transplant.) |
| Overall Survival | From time of drug product infusion up to 24 months | 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. |
| Number of Participants With Integration Site Analysis (ISA) With >30% Clonal Contribution | From time of drug product infusion up to 24 months | 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. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From signing of informed consent to 24 months after the drug product infusion | 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. |
| Number of Participants With Successful Neutrophil Engraftment | From time of drug product infusion up to 24 months | 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. |
| Duration of Transfusion Independence (TI) | From time of drug product infusion up to 24 months | 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. |
Countries
Australia, Thailand, United States
Participant flow
Recruitment details
The study was conducted at 6 centers in the United States, Australia and Thailand between 05 September 2013 (first participant first visit) and 21 February 2018 (last participant last visit).
Pre-assignment details
A total of 19 participants were enrolled in the study and made up the Intent-to-Treat (ITT) population, which included all participants who initiated any study procedures, beginning with mobilization by granulocyte-colony stimulating factor (G-CSF), with or without plerixafor.
Participants by arm
| Arm | Count |
|---|---|
| Non-β0/β0 Participants who had at least 1 mutation in the HBB gene that results in reduced but detectable expression of β-globin: β+ or βE (non-β0/β0 genotype) underwent HSC mobilization with G-CSF and plerixafor, followed by myeloablative conditioning and infusion with LentiGlobin BB305 Drug Product at a dose of \>= 3.0 × 10\^6 CD34+ cells/kg. | 11 |
| β0/β0 Participants who were bi-allelic for mutations in the HBB gene that results in absence of expression of β-globin: β0 (β0/β0 genotype) underwent HSC mobilization with G-CSF and plerixafor, followed by myeloablative conditioning and infusion with LentiGlobin BB305 Drug Product at a dose of \>= 3.0 × 10\^6 CD34+ cells/kg. | 8 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Investigator decision | 1 | 0 |
Baseline characteristics
| Characteristic | β0/β0 | Total | Non-β0/β0 |
|---|---|---|---|
| Age, Continuous | 24.1 Years STANDARD_DEVIATION 7.62 | 23.3 Years STANDARD_DEVIATION 6.82 | 22.7 Years STANDARD_DEVIATION 6.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 16 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 6 Participants | 14 Participants | 8 Participants |
| Race/Ethnicity, Customized Asian/Italian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Female | 6 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 8 | 0 / 19 |
| other Total, other adverse events | 10 / 11 | 8 / 8 | 18 / 19 |
| serious Total, serious adverse events | 6 / 11 | 4 / 8 | 10 / 19 |
Outcome results
Primary
Percentage of Participants Who Achieved Transfusion Independence (TI)
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.
Time frame: From time of drug product infusion up to 24 months
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-β0/β0 | Percentage of Participants Who Achieved Transfusion Independence (TI) | 80.0 Percentage of participants |
| β0/β0 | Percentage of Participants Who Achieved Transfusion Independence (TI) | 12.5 Percentage of participants |
| Overall | Percentage of Participants Who Achieved Transfusion Independence (TI) | 50.0 Percentage of participants |
Primary
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
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.
Time frame: Month 18 to Month 24
Population: Transplant Population (TP) included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-β0/β0 | 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 | 90.0 Percentage of participants |
| β0/β0 | 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 | 87.5 Percentage of participants |
| Overall | 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 | 88.9 Percentage of participants |
Secondary
Duration of Transfusion Independence (TI)
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.
Time frame: From time of drug product infusion up to 24 months
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion. Here, number of participants analyzed refers to the number of participants who reported TI.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-β0/β0 | Duration of Transfusion Independence (TI) | 18.91 Months |
| β0/β0 | Duration of Transfusion Independence (TI) | 16.13 Months |
| Overall | Duration of Transfusion Independence (TI) | 17.28 Months |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: From signing of informed consent to 24 months after the drug product infusion
Population: ITT population included all participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Non-β0/β0 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 10 Participants |
| Non-β0/β0 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 6 Participants |
| β0/β0 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 8 Participants |
| β0/β0 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 4 Participants |
| Overall | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 18 Participants |
| Overall | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 10 Participants |
Secondary
Number of Participants With Integration Site Analysis (ISA) With >30% Clonal Contribution
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.
Time frame: From time of drug product infusion up to 24 months
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Non-β0/β0 | Number of Participants With Integration Site Analysis (ISA) With >30% Clonal Contribution | No | 18 Participants |
| Non-β0/β0 | Number of Participants With Integration Site Analysis (ISA) With >30% Clonal Contribution | Yes | 0 Participants |
Secondary
Number of Participants With Successful Neutrophil Engraftment
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.
Time frame: From time of drug product infusion up to 24 months
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-β0/β0 | Number of Participants With Successful Neutrophil Engraftment | 10 Participants |
| β0/β0 | Number of Participants With Successful Neutrophil Engraftment | 8 Participants |
| Overall | Number of Participants With Successful Neutrophil Engraftment | 18 Participants |
Secondary
Number of Participants With Successful Platelet Engraftment
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.
Time frame: From time of drug product infusion up to 24 months
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-β0/β0 | Number of Participants With Successful Platelet Engraftment | 10 Participants |
| β0/β0 | Number of Participants With Successful Platelet Engraftment | 8 Participants |
| Overall | Number of Participants With Successful Platelet Engraftment | 18 Participants |
Secondary
Overall Survival
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.
Time frame: From time of drug product infusion up to 24 months
Population: ITT population included all participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-β0/β0 | Overall Survival | 100 Percentage of participants |
Secondary
Percentage Change From Baseline in Annualized Number of Packed Red Blood Cells (pRBC) Transfusions at Month 24
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.
Time frame: Baseline, Month 24
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-β0/β0 | Percentage Change From Baseline in Annualized Number of Packed Red Blood Cells (pRBC) Transfusions at Month 24 | -100.00 Percentage of annualized transfusions |
| β0/β0 | Percentage Change From Baseline in Annualized Number of Packed Red Blood Cells (pRBC) Transfusions at Month 24 | -65.80 Percentage of annualized transfusions |
| Overall | Percentage Change From Baseline in Annualized Number of Packed Red Blood Cells (pRBC) Transfusions at Month 24 | -90.74 Percentage of annualized transfusions |
Secondary
Percentage Change From Baseline in Average Annual Packed Red Blood Cells (pRBC) Transfusion Volume at Month 24
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.
Time frame: Baseline, Month 24
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-β0/β0 | Percentage Change From Baseline in Average Annual Packed Red Blood Cells (pRBC) Transfusion Volume at Month 24 | -100.00 Percentage of pRBC transfusion volume |
| β0/β0 | Percentage Change From Baseline in Average Annual Packed Red Blood Cells (pRBC) Transfusion Volume at Month 24 | -71.97 Percentage of pRBC transfusion volume |
| Overall | Percentage Change From Baseline in Average Annual Packed Red Blood Cells (pRBC) Transfusion Volume at Month 24 | -92.38 Percentage of pRBC transfusion volume |
Secondary
Percentage of Participants Detected With Replication-competent Lentivirus (RCL)
Blood samples were analyzed for detection of RCL using RCL co-culture assay.
Time frame: From time of drug product infusion up to 24 months
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-β0/β0 | Percentage of Participants Detected With Replication-competent Lentivirus (RCL) | 0 Percentage of participants |
Secondary
Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24
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 frame: Month 18, Month 24
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Non-β0/β0 | Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24 | Month 18 | 80.0 Percentage of participants |
| Non-β0/β0 | Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24 | Month 24 | 80.0 Percentage of participants |
| β0/β0 | Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24 | Month 18 | 12.5 Percentage of participants |
| β0/β0 | Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24 | Month 24 | 0 Percentage of participants |
| Overall | Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24 | Month 18 | 50.0 Percentage of participants |
| Overall | Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24 | Month 24 | 44.4 Percentage of participants |
Secondary
Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI)
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.
Time frame: From time of drug product infusion up to 24 months
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion. Here, number of participants analyzed refers to the number of participants who reported TI.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-β0/β0 | Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI) | 17.12 Months |
| β0/β0 | Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI) | 17.51 Months |
| Overall | Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI) | 17.51 Months |
Secondary
Time From LentiGlobin BB305 Drug Product Infusion to Last pRBC Transfusion Prior to Achieving Transfusion Independence (TI)
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.
Time frame: From time of drug product infusion up to 24 months
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion. Here, number of participants analyzed refers to the number of participants who reported TI.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-β0/β0 | Time From LentiGlobin BB305 Drug Product Infusion to Last pRBC Transfusion Prior to Achieving Transfusion Independence (TI) | 2.00 Months |
| β0/β0 | Time From LentiGlobin BB305 Drug Product Infusion to Last pRBC Transfusion Prior to Achieving Transfusion Independence (TI) | 1.81 Months |
| Overall | Time From LentiGlobin BB305 Drug Product Infusion to Last pRBC Transfusion Prior to Achieving Transfusion Independence (TI) | 1.81 Months |
Secondary
Time to Neutrophil Engraftment
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.
Time frame: From time of drug product infusion up to 24 months
Population: TP included all participants in the ITT population who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-β0/β0 | Time to Neutrophil Engraftment | 18.5 Days |
| β0/β0 | Time to Neutrophil Engraftment | 19.5 Days |
| Overall | Time to Neutrophil Engraftment | 18.5 Days |
Secondary
Time to Platelet Engraftment
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.
Time frame: From time of drug product infusion up to 24 months
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-β0/β0 | Time to Platelet Engraftment | 50.5 Days |
| β0/β0 | Time to Platelet Engraftment | 36.0 Days |
| Overall | Time to Platelet Engraftment | 39.5 Days |
Secondary
Transplant-related Mortality
Transplant-related mortality was determined by the investigator (any deaths considered related to the transplant.)
Time frame: Through 100 and 365 days post-LentiGlobin BB305 Drug Product infusion
Population: ITT population included all participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-β0/β0 | Transplant-related Mortality | 0 Participants |
Secondary
Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI)
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.
Time frame: From time of drug product infusion up to 24 months
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion. Here, number of participants analyzed refers to the number of participants who reported TI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-β0/β0 | Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) | 10.44 Grams per deciliter (g/dL) | Standard Deviation 1.277 |
| β0/β0 | Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) | 10.11 Grams per deciliter (g/dL) | — |
| Overall | Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) | 10.41 Grams per deciliter (g/dL) | Standard Deviation 1.2 |
Secondary
Weighted Average Nadir Hemoglobin (Hb)
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.
Time frame: Baseline, Month 6 to Month 24
Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-β0/β0 | Weighted Average Nadir Hemoglobin (Hb) | Month 6 to Month 24 | 9.97 Grams per deciliter (g/dL) | Standard Deviation 1.678 |
| Non-β0/β0 | Weighted Average Nadir Hemoglobin (Hb) | Baseline | 8.73 Grams per deciliter (g/dL) | Standard Deviation 1.014 |
| β0/β0 | Weighted Average Nadir Hemoglobin (Hb) | Baseline | 9.38 Grams per deciliter (g/dL) | Standard Deviation 0.431 |
| β0/β0 | Weighted Average Nadir Hemoglobin (Hb) | Month 6 to Month 24 | 8.67 Grams per deciliter (g/dL) | Standard Deviation 0.617 |
| Overall | Weighted Average Nadir Hemoglobin (Hb) | Baseline | 9.02 Grams per deciliter (g/dL) | Standard Deviation 0.855 |
| Overall | Weighted Average Nadir Hemoglobin (Hb) | Month 6 to Month 24 | 9.39 Grams per deciliter (g/dL) | Standard Deviation 1.446 |