Beta-Thalassemia Major, Sickle Cell Disease
Conditions
Brief summary
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).
Interventions
LentiGlobin BB305 Drug Product was administered by intravenous (IV) infusion.
Sponsors
Genetix Biotherapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
1. Be between 5 and 35 years of age, inclusive. 2. Have severe SCD or transfusion dependent beta-thalassemia major, regardless of the genotype with the diagnosis confirmed by Hb studies. Transfusion dependence is defined as requiring at least 100 mL/kg/year of packed red blood cells (pRBCs). 3. Be eligible for allogeneic hematopoietic stem cell transplant (HSCT) based on institutional medical guidelines, but without a matched related donor. 4. Be willing and able, in the Investigator's opinion, to comply with the study procedures outlined in the study protocol. 5. Have been treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history. Participants with severe SCD also must: 6. Have failed to achieve adequate clinical benefit following hydroxyurea treatment with sufficient dosage, for at least 4 months unless this treatment was not indicated or not well tolerated. 7. Have 1 or more of the following poor prognostic risk factors: * Recurrent vaso occlusive crises (at least 2 episodes in the preceding year or in the year prior to start of a regular transfusion program). * Presence of any significant cerebral abnormality on magnetic resonance imaging (MRI) (such as stenosis or occlusions). * Stroke without any severe cognitive disability. * Osteonecrosis of 2 or more joints. * Anti-erythrocyte alloimmunization (\>2 antibodies). * Presence of sickle cell cardiomyopathy documented by Doppler echocardiography. * Acute chest syndrome (at least 2 episodes) defined by an acute event with pneumonia-like symptoms (e.g., cough, fever \[\>38.5°C\], acute dyspnea, expectoration, chest pain, findings upon lung auscultation, tachypnea, or wheezing) and the presence of a new pulmonary infiltrate. Participants with a chronic oxygen saturation \<90% (excluding periods of SCD crisis) or carbon monoxide diffusing capacity (DLco) less than 60% in the absence of an infection should not be included in the study. 8. Participants with severe SCD and cerebral vasculopathy (defined by overt stroke; abnormal transcranial Doppler \[\> 170 cm/sec\]; or occlusion or stenosis in the polygon of Willis; or presence of Moyamoya disease) may be enrolled only with approval by the Comite de Surveillance after review of safety and efficacy data from \>or= 2 SCD participants without cerebral vasculopathy treated with LentiGlobin BB305 Drug Product
Exclusion criteria
1. Availability of a willing 10 /10 matched human leukocyte antigen (HLA) identical sibling hematopoietic cell donor, unless recommendation for enrollment is provided by the Comite de Surveillance following a review of the case. 2. Clinically significant, active bacterial, viral, fungal, or parasitic infection. 3. Contraindication to anesthesia for bone marrow harvesting. 4. Any prior or current malignancy, myeloproliferative or immunodeficiency disorder. 5. A white blood cell (WBC) count \<3×10\^9/L and/or platelet count \<120×10\^9/L. 6. History of major organ damage including: * Liver disease, with transaminase levels \>3× upper limit of normal. * This observation will not be exclusionary if a liver biopsy shows no evidence of extensive bridging fibrosis, cirrhosis, or acute hepatitis. * Histopathological evidence of extensive bridging fibrosis, cirrhosis, or acute hepatitis on liver biopsy. * Heart disease, with a left ventricular ejection fraction \<25%. * Kidney disease with a calculated creatinine clearance \<30% normal value. * Severe iron overload, which in the opinion of the physician is grounds for exclusion. * A cardiac T2\* \<10 ms by magnetic resonance imaging (MRI). * Evidence of clinically significant pulmonary hypertension requiring medical intervention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treated Participants With Successful Neutrophil and Platelet Engraftment | From time of drug product infusion through Month 24 | 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. |
| Time to Successful Neutrophil and Platelet Engraftment | From time of drug product infusion through Month 24 | 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. |
| Incidence of Transplant Related Mortality | From screening through 365 days post-transplant | 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. |
| Number of Participants With Overall Survival (OS) Events | From time of drug product infusion through Month 24 | 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. |
| Percentage of Participants With Vector-Derived Replication-Competent Lentivirus (RCL) | From time of drug product infusion through Month 24 | Blood samples were analyzed for detection of RCL using RCL co-culture assay. |
| Number of Treated Participants With Greater Than (>) 30 Percent (%) Contribution of an Individual Clone As Per Integration Site Analysis (ISA) | From time of drug product infusion through Month 24 | 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. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From date of Informed Consent signing up to Month 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Annualized Number of Packed Red Blood Cell (pRBC) Transfusions | Baseline, From 6 months post-drug product infusion through Month 24 | Percentage change from baseline in annualized number of pRBC transfusions from 6 months post-drug product infusion through last visit were reported. |
| Number of Participants With Vaso-Occlusive Crisis (VOC) and/or Acute Chest Syndrome (ACS) Events Post Drug Product Infusion in Sickle Cell Disease Participants | From time of drug product infusion through Month 24 | Number of VOCs, ACS, and vaso-occlusive events (VOEs; which included both VOC and ACS) through 24 months after drug product infusion. |
| Percentage of Treated Participants With Transfusion-Dependent β-Thalassemia (TDT) Who Achieved Transfusion Independence (TI) | From time of drug product infusion through Month 24 | 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. |
| Vector Copy Number (VCN) in Peripheral Blood | From time of drug product infusion through Month 24 | 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. |
| Therapeutic Globin Expression Measured by Hb Containing β^A -T87Q Globin (HbA^T87Q) in Peripheral Blood | From time of drug product infusion through Month 24 | 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. |
| Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT) | From time of drug product infusion through Month 24 | 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. |
| Duration of Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT) | From time of drug product infusion through Month 24 | 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. |
| 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) | From time of drug product infusion through Month 24 | 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. |
| Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT) | From time of drug product infusion through Month 24 | 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. |
| Weighted Average Nadir Hemoglobin (Hb) in Participants With Transfusion-Dependent β-Thalassemia (TDT) | From 6 months post-drug product infusion through 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 was used as the Hb nadir. Hb values on the day of the transfusion were considered for nadir calculations. |
| Percentage Change From Baseline in Annualized Packed Red Blood Cell (pRBC) Transfusion Volume | Baseline, From 6 months post-drug product infusion through Month 24 | Percent change from baseline in the average annual transfusion volume from 6 months post-drug product infusion through last visit were reported. |
Countries
France
Participant flow
Recruitment details
This study was conducted at a single site in France between 07 June 2013 (First participant signed informed consent) and 26 February 2019 (Last participant last visit).
Pre-assignment details
A total of 7 participants were treated in a single arm and completed the study. Data was planned, analyzed and reported separately for 3 participants with Sickle Cell Disease (SCD) and 4 participants with transfusion-dependent β-thalassemia (TDT).
Participants by arm
| Arm | Count |
|---|---|
| LentiGlobin BB305 Drug Product for SCD Following myeloablative conditioning with a dose (dose may be adjusted as per protocol) of 3.2 milligram per kilogram per day (mg/kg/day) busulfan intravenous (IV) for 4 consecutive days and subsequent daily monitoring of busulfan levels for confirmation of adequate washout, a single dose of greater than or equal to (\> or =) 2.0×10\^6 cluster of differentiation (CD) 34+ cells/kg LentiGlobin BB305 Drug Product was administered to participants with SCD by IV infusion. | 3 |
| LentiGlobin BB305 Drug Product for TDT Following myeloablative conditioning with a dose (dose may be adjusted as per protocol) of 3.2 mg/kg/day busulfan Intravenous (IV) for 4 consecutive days and subsequent daily monitoring of busulfan levels for confirmation of adequate washout, a single dose of \> or =3.0 × 10\^6 CD34+ cells/kg LentiGlobin BB305 Drug Product (betibeglogene autotemcel) was administered to participants with TDT by IV infusion. | 4 |
| Total | 7 |
Baseline characteristics
| Characteristic | LentiGlobin BB305 Drug Product for SCD | LentiGlobin BB305 Drug Product for TDT | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 3 / 3 | 3 / 4 |
Outcome results
Primary
Incidence of Transplant Related Mortality
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.
Time frame: From screening through 365 days post-transplant
Population: This outcome measure was evaluated in the Transplant Population (TP).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Incidence of Transplant Related Mortality | 0 Number of deaths reported |
| LentiGlobin BB305 Drug Product for TDT | Incidence of Transplant Related Mortality | 0 Number of deaths reported |
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: From date of Informed Consent signing up to Month 24
Population: This outcome measure was evaluated in the ITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of Participants with any Adverse Event | 3 Participants |
| LentiGlobin BB305 Drug Product for SCD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with any SAE | 3 Participants |
| LentiGlobin BB305 Drug Product for TDT | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of Participants with any Adverse Event | 4 Participants |
| LentiGlobin BB305 Drug Product for TDT | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with any SAE | 3 Participants |
Primary
Number of Participants With Overall Survival (OS) Events
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.
Time frame: From time of drug product infusion through Month 24
Population: Intent to Treat (ITT) population consisted of all participants who initiated any study procedures, beginning with mobilization (by Granulocyte colony stimulating factor \[G-CSF\] with or without plerixafor), or bone marrow harvest.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Number of Participants With Overall Survival (OS) Events | Censored Participants | 3 Participants |
| LentiGlobin BB305 Drug Product for SCD | Number of Participants With Overall Survival (OS) Events | Participants reported OS events | 0 Participants |
| LentiGlobin BB305 Drug Product for TDT | Number of Participants With Overall Survival (OS) Events | Censored Participants | 4 Participants |
| LentiGlobin BB305 Drug Product for TDT | Number of Participants With Overall Survival (OS) Events | Participants reported OS events | 0 Participants |
Primary
Number of Treated Participants With Greater Than (>) 30 Percent (%) Contribution of an Individual Clone As Per Integration Site Analysis (ISA)
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.
Time frame: From time of drug product infusion through Month 24
Population: This outcome measure was evaluated in the Transplant Population (TP).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Number of Treated Participants With Greater Than (>) 30 Percent (%) Contribution of an Individual Clone As Per Integration Site Analysis (ISA) | 0 Participants |
| LentiGlobin BB305 Drug Product for TDT | Number of Treated Participants With Greater Than (>) 30 Percent (%) Contribution of an Individual Clone As Per Integration Site Analysis (ISA) | 0 Participants |
Primary
Number of Treated Participants With Successful Neutrophil and Platelet Engraftment
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.
Time frame: From time of drug product infusion through Month 24
Population: Transplant Population (TP) included all participants in the Intent to treat population who underwent LentiGlobin BB305 Drug Product infusion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Number of Treated Participants With Successful Neutrophil and Platelet Engraftment | Participants with Neutrophil Engraftment | 3 Participants |
| LentiGlobin BB305 Drug Product for SCD | Number of Treated Participants With Successful Neutrophil and Platelet Engraftment | Participants with Platelet Engraftment | 3 Participants |
| LentiGlobin BB305 Drug Product for TDT | Number of Treated Participants With Successful Neutrophil and Platelet Engraftment | Participants with Neutrophil Engraftment | 4 Participants |
| LentiGlobin BB305 Drug Product for TDT | Number of Treated Participants With Successful Neutrophil and Platelet Engraftment | Participants with Platelet Engraftment | 4 Participants |
Primary
Percentage of Participants With Vector-Derived 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 through Month 24
Population: This outcome measure was evaluated in the ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Percentage of Participants With Vector-Derived Replication-Competent Lentivirus (RCL) | 0 Percentage of participants |
| LentiGlobin BB305 Drug Product for TDT | Percentage of Participants With Vector-Derived Replication-Competent Lentivirus (RCL) | 0 Percentage of participants |
Primary
Time to Successful Neutrophil and Platelet Engraftment
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.
Time frame: From time of drug product infusion through Month 24
Population: This outcome measure was evaluated in the Transplant Population (TP).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Time to Successful Neutrophil and Platelet Engraftment | Time to Neutrophil Engraftment | 32 Days |
| LentiGlobin BB305 Drug Product for SCD | Time to Successful Neutrophil and Platelet Engraftment | Time to Platelet Engraftment | 51 Days |
| LentiGlobin BB305 Drug Product for TDT | Time to Successful Neutrophil and Platelet Engraftment | Time to Neutrophil Engraftment | 16.5 Days |
| LentiGlobin BB305 Drug Product for TDT | Time to Successful Neutrophil and Platelet Engraftment | Time to Platelet Engraftment | 23 Days |
Secondary
Duration of Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
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.
Time frame: From time of drug product infusion through Month 24
Population: This outcome measure was evaluated only in Transplant Population (TP) with TDT. The number of participants analyzed signifies participants who were evaluable for this specific outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Duration of Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT) | 21.7 Month |
Secondary
Number of Participants With Vaso-Occlusive Crisis (VOC) and/or Acute Chest Syndrome (ACS) Events Post Drug Product Infusion in Sickle Cell Disease Participants
Number of VOCs, ACS, and vaso-occlusive events (VOEs; which included both VOC and ACS) through 24 months after drug product infusion.
Time frame: From time of drug product infusion through Month 24
Population: This outcome measure was evaluated in ITT population. This outcome measure was only planned to evaluate in SCD participants. Events of VOC and ACS were from same participant.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Number of Participants With Vaso-Occlusive Crisis (VOC) and/or Acute Chest Syndrome (ACS) Events Post Drug Product Infusion in Sickle Cell Disease Participants | Vaso-Occlusive Crisis (VOC) | 1 Participants |
| LentiGlobin BB305 Drug Product for SCD | Number of Participants With Vaso-Occlusive Crisis (VOC) and/or Acute Chest Syndrome (ACS) Events Post Drug Product Infusion in Sickle Cell Disease Participants | Acute Chest Syndrome (ACS) | 1 Participants |
Secondary
Percentage Change From Baseline in Annualized Number of Packed Red Blood Cell (pRBC) Transfusions
Percentage change from baseline in annualized number of pRBC transfusions from 6 months post-drug product infusion through last visit were reported.
Time frame: Baseline, From 6 months post-drug product infusion through Month 24
Population: This outcome measure was evaluated in the Transplant Population (TP).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Percentage Change From Baseline in Annualized Number of Packed Red Blood Cell (pRBC) Transfusions | -100.0 percentage change in pRBC transfusion |
| LentiGlobin BB305 Drug Product for TDT | Percentage Change From Baseline in Annualized Number of Packed Red Blood Cell (pRBC) Transfusions | -100.0 percentage change in pRBC transfusion |
Secondary
Percentage Change From Baseline in Annualized Packed Red Blood Cell (pRBC) Transfusion Volume
Percent change from baseline in the average annual transfusion volume from 6 months post-drug product infusion through last visit were reported.
Time frame: Baseline, From 6 months post-drug product infusion through Month 24
Population: This outcome measure was evaluated in the Transplant Population (TP).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Percentage Change From Baseline in Annualized Packed Red Blood Cell (pRBC) Transfusion Volume | -100.0 percent change in Annualized pRBC volume |
| LentiGlobin BB305 Drug Product for TDT | Percentage Change From Baseline in Annualized Packed Red Blood Cell (pRBC) Transfusion Volume | -100.0 percent change in Annualized pRBC volume |
Secondary
Percentage of Treated Participants With Transfusion-Dependent β-Thalassemia (TDT) Who Achieved Transfusion Independence (TI)
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.
Time frame: From time of drug product infusion through Month 24
Population: This outcome measure was evaluated only in Transplant Population (TP) with TDT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Percentage of Treated Participants With Transfusion-Dependent β-Thalassemia (TDT) Who Achieved Transfusion Independence (TI) | 75 Percentage of participants |
Secondary
Therapeutic Globin Expression Measured by Hb Containing β^A -T87Q Globin (HbA^T87Q) in Peripheral Blood
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.
Time frame: From time of drug product infusion through Month 24
Population: This outcome measure was evaluated in the Transplant Population (TP).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Therapeutic Globin Expression Measured by Hb Containing β^A -T87Q Globin (HbA^T87Q) in Peripheral Blood | 2.947 grams per deciliter (g/dL) | Standard Deviation 2.4415 |
| LentiGlobin BB305 Drug Product for TDT | Therapeutic Globin Expression Measured by Hb Containing β^A -T87Q Globin (HbA^T87Q) in Peripheral Blood | 8.287 grams per deciliter (g/dL) | Standard Deviation 1.5758 |
Secondary
Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
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.
Time frame: From time of drug product infusion through Month 24
Population: This outcome measure was evaluated only in Transplant Population (TP) with TDT. The number of participants analyzed signifies participants who were evaluable for this specific outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT) | 14.9 Month |
Secondary
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)
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.
Time frame: From time of drug product infusion through Month 24
Population: This outcome measure was evaluated only in Transplant Population (TP) with TDT. The number of participants analyzed signifies participants who were evaluable for this specific outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | 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) | 11 Days |
Secondary
Vector Copy Number (VCN) in Peripheral Blood
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.
Time frame: From time of drug product infusion through Month 24
Population: This outcome measure was evaluated in the Transplant Population (TP).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Vector Copy Number (VCN) in Peripheral Blood | 0.898 copies per diploid genome (c/dg) | Standard Deviation 1.1655 |
| LentiGlobin BB305 Drug Product for TDT | Vector Copy Number (VCN) in Peripheral Blood | 1.796 copies per diploid genome (c/dg) | Standard Deviation 1.3665 |
Secondary
Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
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.
Time frame: From time of drug product infusion through Month 24
Population: This outcome measure was evaluated only in Transplant Population (TP) with TDT. The number of participants analyzed signifies participants who were evaluable for this specific outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT) | 11.3 grams per deciliter (g/dL) |
Secondary
Weighted Average Nadir Hemoglobin (Hb) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
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.
Time frame: From 6 months post-drug product infusion through Month 24
Population: This outcome measure was evaluated only in Transplant Population (TP) with TDT.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product for SCD | Weighted Average Nadir Hemoglobin (Hb) in Participants With Transfusion-Dependent β-Thalassemia (TDT) | 11 grams per deciliter (g/dL) |