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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-000695-42 | EudraCT Number |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LentiGlobin BB305 Drug Product | Experimental | Following myeloablative conditioning with IV busulfan for 4 consecutive days (dose may be adjusted as per protocol) and subsequent daily monitoring of busulfan levels for confirmation of adequate washout, a single dose cluster of differentiation (CD) 34+ cells/kg LentiGlobin BB305 Drug Product was administered to participants by IV infusion. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LentiGlobin BB305 Drug Product | Drug | LentiGlobin BB305 Drug Product was administered by intravenous (IV) infusion. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | From time of drug product infusion through Month 24 |
| 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. | From time of drug product infusion through Month 24 |
| 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. | From screening through 365 days post-transplant |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Be between 5 and 35 years of age, inclusive.
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).
Be eligible for allogeneic hematopoietic stem cell transplant (HSCT) based on institutional medical guidelines, but without a matched related donor.
Be willing and able, in the Investigator's opinion, to comply with the study procedures outlined in the study protocol.
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:
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.
Have 1 or more of the following poor prognostic risk factors:
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:
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.
Clinically significant, active bacterial, viral, fungal, or parasitic infection.
Contraindication to anesthesia for bone marrow harvesting.
Any prior or current malignancy, myeloproliferative or immunodeficiency disorder.
A white blood cell (WBC) count <3×10^9/L and/or platelet count <120×10^9/L.
History of major organ damage including:
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Antoine Ribeil, MD | bluebird bio, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Paris | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35075288 | Derived | Magrin E, Semeraro M, Hebert N, Joseph L, Magnani A, Chalumeau A, Gabrion A, Roudaut C, Marouene J, Lefrere F, Diana JS, Denis A, Neven B, Funck-Brentano I, Negre O, Renolleau S, Brousse V, Kiger L, Touzot F, Poirot C, Bourget P, El Nemer W, Blanche S, Treluyer JM, Asmal M, Walls C, Beuzard Y, Schmidt M, Hacein-Bey-Abina S, Asnafi V, Guichard I, Poiree M, Monpoux F, Touraine P, Brouzes C, de Montalembert M, Payen E, Six E, Ribeil JA, Miccio A, Bartolucci P, Leboulch P, Cavazzana M. Long-term outcomes of lentiviral gene therapy for the beta-hemoglobinopathies: the HGB-205 trial. Nat Med. 2022 Jan;28(1):81-88. doi: 10.1038/s41591-021-01650-w. Epub 2022 Jan 24. | |
| 29669226 |
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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).
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 19, 2016 | Feb 26, 2020 |
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| From time of drug product infusion through Month 24 |
| Percentage of Participants With Vector-Derived Replication-Competent Lentivirus (RCL) | Blood samples were analyzed for detection of RCL using RCL co-culture assay. | From time of drug product infusion through Month 24 |
| 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. | From time of drug product infusion through Month 24 |
| 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. | From date of Informed Consent signing up to Month 24 |
| From time of drug product infusion through Month 24 |
| 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. | From time of drug product infusion through Month 24 |
| 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. | From time of drug product infusion through Month 24 |
| 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. | From time of drug product infusion through Month 24 |
| 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. | From time of drug product infusion through Month 24 |
| 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. | From 6 months post-drug product infusion through Month 24 |
| 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. | Baseline, From 6 months post-drug product infusion through Month 24 |
| 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. | Baseline, From 6 months post-drug product infusion through Month 24 |
| 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. | From time of drug product infusion through Month 24 |
| 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. | From time of drug product infusion through Month 24 |
| 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. | From time of drug product infusion through Month 24 |
| Derived |
| Thompson AA, Walters MC, Kwiatkowski J, Rasko JEJ, Ribeil JA, Hongeng S, Magrin E, Schiller GJ, Payen E, Semeraro M, Moshous D, Lefrere F, Puy H, Bourget P, Magnani A, Caccavelli L, Diana JS, Suarez F, Monpoux F, Brousse V, Poirot C, Brouzes C, Meritet JF, Pondarre C, Beuzard Y, Chretien S, Lefebvre T, Teachey DT, Anurathapan U, Ho PJ, von Kalle C, Kletzel M, Vichinsky E, Soni S, Veres G, Negre O, Ross RW, Davidson D, Petrusich A, Sandler L, Asmal M, Hermine O, De Montalembert M, Hacein-Bey-Abina S, Blanche S, Leboulch P, Cavazzana M. Gene Therapy in Patients with Transfusion-Dependent beta-Thalassemia. N Engl J Med. 2018 Apr 19;378(16):1479-1493. doi: 10.1056/NEJMoa1705342. |
| 28249145 | Derived | Ribeil JA, Hacein-Bey-Abina S, Payen E, Magnani A, Semeraro M, Magrin E, Caccavelli L, Neven B, Bourget P, El Nemer W, Bartolucci P, Weber L, Puy H, Meritet JF, Grevent D, Beuzard Y, Chretien S, Lefebvre T, Ross RW, Negre O, Veres G, Sandler L, Soni S, de Montalembert M, Blanche S, Leboulch P, Cavazzana M. Gene Therapy in a Patient with Sickle Cell Disease. N Engl J Med. 2017 Mar 2;376(9):848-855. doi: 10.1056/NEJMoa1609677. |
| FG001 | 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. |
| COMPLETED |
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| NOT COMPLETED |
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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.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
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| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
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| 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. | Transplant Population (TP) included all participants in the Intent to treat population who underwent LentiGlobin BB305 Drug Product infusion. | Posted | Count of Participants | Participants | From time of drug product infusion through Month 24 |
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| 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. | This outcome measure was evaluated in the Transplant Population (TP). | Posted | Median | Full Range | Days | From time of drug product infusion through Month 24 |
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| 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. | This outcome measure was evaluated in the Transplant Population (TP). | Posted | Number | Number of deaths reported | From screening through 365 days post-transplant |
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| 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. | 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. | Posted | Count of Participants | Participants | From time of drug product infusion through Month 24 |
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| Primary | Percentage of Participants With Vector-Derived Replication-Competent Lentivirus (RCL) | Blood samples were analyzed for detection of RCL using RCL co-culture assay. | This outcome measure was evaluated in the ITT population. | Posted | Number | Percentage of participants | From time of drug product infusion through Month 24 |
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| 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. | This outcome measure was evaluated in the Transplant Population (TP). | Posted | Count of Participants | Participants | From time of drug product infusion through Month 24 |
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| 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. | This outcome measure was evaluated in the ITT population. | Posted | Count of Participants | Participants | From date of Informed Consent signing up to Month 24 |
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| 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. | This outcome measure was evaluated only in Transplant Population (TP) with TDT. | Posted | Number | Percentage of participants | From time of drug product infusion through Month 24 |
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| 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. | 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. | Posted | Median | Full Range | grams per deciliter (g/dL) | From time of drug product infusion through Month 24 |
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| 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. | 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. | Posted | Median | Full Range | Month | From time of drug product infusion through Month 24 |
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| 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. | 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. | Posted | Median | Full Range | Days | From time of drug product infusion through Month 24 |
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| 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. | 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. | Posted | Median | Full Range | Month | From time of drug product infusion through Month 24 |
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| 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. | This outcome measure was evaluated only in Transplant Population (TP) with TDT. | Posted | Median | Full Range | grams per deciliter (g/dL) | From 6 months post-drug product infusion through Month 24 |
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| 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. | This outcome measure was evaluated in the Transplant Population (TP). | Posted | Median | Full Range | percent change in Annualized pRBC volume | Baseline, From 6 months post-drug product infusion through Month 24 |
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| 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. | This outcome measure was evaluated in the Transplant Population (TP). | Posted | Median | Full Range | percentage change in pRBC transfusion | Baseline, From 6 months post-drug product infusion through Month 24 |
| |||||||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Count of Participants | Participants | From time of drug product infusion through Month 24 |
|
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| 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. | This outcome measure was evaluated in the Transplant Population (TP). | Posted | Mean | Standard Deviation | grams per deciliter (g/dL) | From time of drug product infusion through Month 24 |
| |||||||||||||||||||||||||||||||||||||
| 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. | This outcome measure was evaluated in the Transplant Population (TP). | Posted | Mean | Standard Deviation | copies per diploid genome (c/dg) | From time of drug product infusion through Month 24 |
|
From date of Informed Consent signing up to Month 24
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 3 | 3 | 3 | 3 | 3 |
| EG001 | 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. | 0 | 4 | 3 | 4 | 4 | 4 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Acute chest syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Sickle cell anaemia with crisis | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Major depression | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Staphylococcal bacteraemia | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hot flush | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Non-systematic Assessment |
| |
| Xerosis | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Puncture site pain | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Catheter site pain | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Feeling cold | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hypothermia | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Injection site inflammation | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Disturbance in attention | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Ovarian cyst | Reproductive system and breast disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Premature menopause | Reproductive system and breast disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
| |
| Catheter site pain | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Staphylococcus test positive | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Aspergillus test positive | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Dolichocolon | Congenital, familial and genetic disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Restrictive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Sickle cell anaemia with crisis | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Anal fissure | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Lip dry | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Anal inflammation | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Melanoderma | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Genital candidiasis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Wound infection fungal | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Mastitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Medical Director | bluebird bio, Inc. | 339-499-9300 | medinfo@bluebirdbio.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 22, 2019 | Feb 26, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D017086 | beta-Thalassemia |
| D000755 | Anemia, Sickle Cell |
| ID | Term |
|---|---|
| D013789 | Thalassemia |
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
| OG001 | 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. |
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
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|
|
|
|
|
|
|
|
|
|