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A Study Evaluating the Safety and Efficacy of the LentiGlobin BB305 Drug Product in β-Thalassemia Major Participants

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ClinicalTrials.gov Identifier: NCT01745120
Recruitment Status : Completed
First Posted : December 7, 2012
Results First Posted : May 8, 2019
Last Update Posted : May 8, 2019
Sponsor:
Information provided by (Responsible Party):
bluebird bio

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition β-thalassemia Major
Intervention Genetic: LentiGlobin BB305 Drug Product
Enrollment 19
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.
Arm/Group Title Non-β0/β0 β0/β0
Hide Arm/Group Description Participants who had at least 1 mutation in the HBB gene that results in reduced but detectable expression of beta(β)-globin: β+ or βE (non-β0/β0 genotype) underwent hematopoietic stem cell (HSC) mobilization with G-CSF and plerixafor, followed by myeloablative conditioning and infusion with LentiGlobin BB305 Drug Product at a dose of greater than or equal to (>=) 3.0 × 10^6 CD34+ cells per kilogram (cells/kg). 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.
Period Title: Overall Study
Started [1] 11 8
Completed 10 8
Not Completed 1 0
Reason Not Completed
Investigator decision             1             0
[1]
Started = ITT
Arm/Group Title Non-β0/β0 β0/β0 Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 11 8 19
Hide Baseline Analysis Population Description
Intent-to-Treat Population (ITT) included all participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 11 participants 8 participants 19 participants
22.7  (6.50) 24.1  (7.62) 23.3  (6.82)
[1]
Measure Description: Age at the time of informed consent or assent (applicable for participants less than 18 years old) was reported
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 8 participants 19 participants
Female
7
  63.6%
6
  75.0%
13
  68.4%
Male
4
  36.4%
2
  25.0%
6
  31.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 8 participants 19 participants
Hispanic or Latino
1
   9.1%
0
   0.0%
1
   5.3%
Not Hispanic or Latino
9
  81.8%
7
  87.5%
16
  84.2%
Unknown or Not Reported
1
   9.1%
1
  12.5%
2
  10.5%
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 8 participants 19 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
8
  72.7%
6
  75.0%
14
  73.7%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
2
  18.2%
2
  25.0%
4
  21.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Asian/Italian
1
   9.1%
0
   0.0%
1
   5.3%
[1]
Measure Description: Race of the participants was reported.
1.Primary Outcome
Title 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
Hide Description Percentage of participants with sustained production of >=2.0 grams per deciliter (g/dL) of hemoglobin A (HbA) containing βA-T87Q-globin (HbAT87Q) for 6 months (Month 18 to Month 24) was reported.
Time Frame Month 18 to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 10 8 18
Measure Type: Number
Unit of Measure: Percentage of participants
90.0 87.5 88.9
2.Primary Outcome
Title Percentage of Participants Who Achieved Transfusion Independence (TI)
Hide Description TI was defined as a weighted average hemoglobin (Hb) >= 9 g/dL without any packed red blood cells (pRBC) transfusions for a continuous period of >=12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Percentage of participants who achieved TI from time of drug product infusion up to 24 months was reported.
Time Frame From time of drug product infusion up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 10 8 18
Measure Type: Number
Unit of Measure: Percentage of participants
80.0 12.5 50.0
3.Secondary Outcome
Title Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24
Hide Description TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion.
Time Frame Month 18, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 10 8 18
Measure Type: Number
Unit of Measure: Percentage of participants
Month 18 80.0 12.5 50.0
Month 24 80.0 0 44.4
4.Secondary Outcome
Title Duration of Transfusion Independence (TI)
Hide Description TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Time period of TI will start when participants achieve a Hb >= 9 g/dL with no transfusions in the preceding 60 days. Duration of TI was calculated as the time from the start of TI (i.e. first Hb >= 9 g/dL with no transfusions in the preceding 60 days) up to the last available Hb at which the TI criteria are still met.
Time Frame From time of drug product infusion up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 8 1 9
Median (Full Range)
Unit of Measure: Months
18.91
(15.2 to 21.4)
16.13
(16.13 to 16.13)
17.28
(15.2 to 21.4)
5.Secondary Outcome
Title Time From LentiGlobin BB305 Drug Product Infusion to Last pRBC Transfusion Prior to Achieving Transfusion Independence (TI)
Hide Description TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Time From LentiGlobin BB305 Drug Product Infusion to last pRBC transfusion prior to achieving TI was reported.
Time Frame From time of drug product infusion up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 8 1 9
Median (Full Range)
Unit of Measure: Months
2.00
(0.3 to 5.8)
1.81
(1.81 to 1.81)
1.81
(0.3 to 5.8)
6.Secondary Outcome
Title Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI)
Hide Description TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Time from drug product infusion to initial achievement of TI was calculated as the time from drug product infusion to the first Hb at which a participant can be declared as TI.
Time Frame From time of drug product infusion up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 8 1 9
Median (Full Range)
Unit of Measure: Months
17.12
(15.0 to 20.9)
17.51
(17.51 to 17.51)
17.51
(15.0 to 20.9)
7.Secondary Outcome
Title Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI)
Hide Description The weighted average Hb is an average area under the curve during the period of TI, from the start of TI when the Hb is first >= 9 g/dL with no transfusions in the preceding 60 days to the last available Hb at which the TI criteria are still met. TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Weighted average Hb during the period of TI was reported.
Time Frame From time of drug product infusion up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 8 1 9
Mean (Standard Deviation)
Unit of Measure: Grams per deciliter (g/dL)
10.44  (1.277) 10.11 [1]   (NA) 10.41  (1.200)
[1]
Standard deviation was not calculated due to less number of participants.
8.Secondary Outcome
Title Percentage Change From Baseline in Annualized Number of Packed Red Blood Cells (pRBC) Transfusions at Month 24
Hide Description The annualized number of pRBC transfusions over the 2 year period prior to drug product infusion was compared to the annualized number of pRBC transfusions during the Month 6 to Month 24 period post drug product infusion and the percentage change was reported.
Time Frame Baseline, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 10 8 18
Median (Full Range)
Unit of Measure: Percentage of annualized transfusions
-100.00
(-100.0 to -20.7)
-65.80
(-96.2 to 2.5)
-90.74
(-100.0 to 2.5)
9.Secondary Outcome
Title Percentage Change From Baseline in Average Annual Packed Red Blood Cells (pRBC) Transfusion Volume at Month 24
Hide Description The annualized volume of pRBC transfusions over the 2 year period prior to drug product infusion was compared to the annualized volume of pRBC transfusions in the Month 6 to Month 24 period post drug product Infusion and the percentage change from baseline was reported.
Time Frame Baseline, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 10 8 18
Median (Full Range)
Unit of Measure: Percentage of pRBC transfusion volume
-100.00
(-100.0 to -26.8)
-71.97
(-97.8 to -8.3)
-92.38
(-100.0 to -8.3)
10.Secondary Outcome
Title Weighted Average Nadir Hemoglobin (Hb)
Hide Description Weighted average Hb nadir was defined as an average area under the curve where the Hb closest but within 3 days prior to a transfusion is used as the Hb nadir. If there is a period of more than 60 days without a pRBC transfusion, all Hb records between Day 61 and day of last visit or next transfusion (inclusive) were also considered as nadirs. The weighted average nadir Hb during the period of Month 6 to Month 24 was compared to the weighted average nadir Hb during the 2 years prior to enrollment.
Time Frame Baseline, Month 6 to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 10 8 18
Mean (Standard Deviation)
Unit of Measure: Grams per deciliter (g/dL)
Baseline 8.73  (1.014) 9.38  (0.431) 9.02  (0.855)
Month 6 to Month 24 9.97  (1.678) 8.67  (0.617) 9.39  (1.446)
11.Secondary Outcome
Title Number of Participants With Successful Neutrophil Engraftment
Hide Description Neutrophil engraftment was defined as achieving 3 consecutive absolute neutrophil count (ANC) >= 0.5 × 10^9/L on different days after a post-transplant value of < 0.5 × 10^9/L within 42 days after drug product infusion.
Time Frame From time of drug product infusion up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 10 8 18
Measure Type: Count of Participants
Unit of Measure: Participants
10
 100.0%
8
 100.0%
18
 100.0%
12.Secondary Outcome
Title Time to Neutrophil Engraftment
Hide Description Time to neutrophil engraftment was defined as the time to the first of 3 consecutive absolute neutrophil count (ANC) >= 0.5 × 10^9/L obtained on different days after a post-transplant value of < 0.5 × 10^9/L. The Day of neutrophil engraftment is the first day of the 3 consecutive measurements, where Day 1 is the day of drug product infusion.
Time Frame From time of drug product infusion up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
TP included all participants in the ITT population who underwent LentiGlobin BB305 Drug Product infusion.
Arm/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 10 8 18
Median (Full Range)
Unit of Measure: Days
18.5
(14 to 27)
19.5
(15 to 30)
18.5
(14 to 30)
13.Secondary Outcome
Title Number of Participants With Successful Platelet Engraftment
Hide Description Platelet engraftment was defined as achieving 3 consecutive platelet values >= 20 × 10^9/L on different days after a post-transplant value of < 20 × 10^9/L, while no platelet transfusions administered for 7 days immediately preceding and during the evaluation period.
Time Frame From time of drug product infusion up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 10 8 18
Measure Type: Count of Participants
Unit of Measure: Participants
10
 100.0%
8
 100.0%
18
 100.0%
14.Secondary Outcome
Title Time to Platelet Engraftment
Hide Description Time to platelet engraftment was defined as achieving of first 3 consecutive platelet values >= 20 × 10^9/L obtained on different days after a post-transplant value of < 20 × 10^9/L, while no platelet transfusions administered for 7 days immediately preceding and during the evaluation period. The day of platelet engraftment is the first day of the 3 consecutive measurements, where Day 1 is the day of drug product infusion.
Time Frame From time of drug product infusion up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 10 8 18
Median (Full Range)
Unit of Measure: Days
50.5
(19 to 191)
36.0
(31 to 55)
39.5
(19 to 191)
15.Secondary Outcome
Title Transplant-related Mortality
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor.
Arm/Group Title Overall
Hide Arm/Group Description:
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
16.Secondary Outcome
Title Overall Survival
Hide Description Overall survival was defined as time from date of LentiGlobin BB305 Drug Product infusion (Day 1) to date of death. Overall survival was censored at the date of last visit if the participant was still alive. Percentage of participants who survived throughout the study were reported.
Time Frame From time of drug product infusion up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor.
Arm/Group Title Overall
Hide Arm/Group Description:
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 19
Measure Type: Number
Unit of Measure: Percentage of participants
100
17.Secondary Outcome
Title Percentage of Participants Detected With Replication-competent Lentivirus (RCL)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Overall
Hide Arm/Group Description:
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: Percentage of participants
0
18.Secondary Outcome
Title Number of Participants With Integration Site Analysis (ISA) With >30% Clonal Contribution
Hide Description Linear amplification-mediated polymerase chain reaction (LAM-PCR) coupled with next generation sequencing and subsequent (semi-) automated data mining allowed high-throughput analysis of vector integration site (IS) in blood cells from treated participants at multiple time points. ISs detected in peripheral blood cells at early time points generally were due to the expansion of transduced short-term progenitor stem cell clones, and gradually shift to include sites detected due to expansion of transduced long-term stem cell clones. An efficient transduction procedure was anticipated to give rise to a polyclonal population in the participant, reflected by the detection of multiple IS. Additionally, ISA allowed monitoring of the relative contribution of individual clones over time. Number of participants who had IS that contributed to >=30% of the total clones at any time was used as a first step to investigating whether clonal dominance was achieved.
Time Frame From time of drug product infusion up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Overall
Hide Arm/Group Description:
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 18
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
0
   0.0%
No
18
 100.0%
19.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was defined as any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was any AE, occurring at any dose and regardless of causality that: results in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect.
Time Frame From signing of informed consent to 24 months after the drug product infusion
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor.
Arm/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description:
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.
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.
Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
Overall Number of Participants Analyzed 11 8 19
Measure Type: Count of Participants
Unit of Measure: Participants
Adverse Events
10
  90.9%
8
 100.0%
18
  94.7%
Serious Adverse Events
6
  54.5%
4
  50.0%
10
  52.6%
Time Frame From signing of informed consent to 24 months after the drug product infusion
Adverse Event Reporting Description ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
 
Arm/Group Title Non-β0/β0 β0/β0 Overall
Hide Arm/Group Description 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. 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. Participants with a β0/β0 genotype or non-β0/β0 genotypes 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.
All-Cause Mortality
Non-β0/β0 β0/β0 Overall
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/11 (0.00%)   0/8 (0.00%)   0/19 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Non-β0/β0 β0/β0 Overall
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/11 (54.55%)   4/8 (50.00%)   10/19 (52.63%) 
Blood and lymphatic system disorders       
Anaemia * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Cardiac disorders       
Intracardiac thrombus * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Hepatobiliary disorders       
Venoocclusive liver disease * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Infections and infestations       
Appendicitis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Asymptomatic HIV infection * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Cat scratch disease * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Catheter site infection * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Cellulitis * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Diarrhoea infectious * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Gastroenteritis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Viral infection * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Injury, poisoning and procedural complications       
Post procedural haemorrhage * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Metabolism and nutrition disorders       
Hyperglycaemia * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Vascular disorders       
Vena cava thrombosis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
1
Term from vocabulary, MedDRA 19.0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Non-β0/β0 β0/β0 Overall
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/11 (90.91%)   8/8 (100.00%)   18/19 (94.74%) 
Blood and lymphatic system disorders       
Thrombocytopenia * 1  10/11 (90.91%)  8/8 (100.00%)  18/19 (94.74%) 
Anaemia * 1  9/11 (81.82%)  8/8 (100.00%)  17/19 (89.47%) 
Febrile neutropenia * 1  7/11 (63.64%)  4/8 (50.00%)  11/19 (57.89%) 
Neutropenia * 1  6/11 (54.55%)  4/8 (50.00%)  10/19 (52.63%) 
Leukopenia * 1  5/11 (45.45%)  1/8 (12.50%)  6/19 (31.58%) 
Leukocytosis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Lymphadenitis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Lymphopenia * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Neutrophilia * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Splenomegaly * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Cardiac disorders       
Cardiac flutter * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Palpitations * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Sinus tachycardia * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Eye disorders       
Conjunctivitis * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Myopia * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Punctate keratitis * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Gastrointestinal disorders       
Stomatitis * 1  8/11 (72.73%)  5/8 (62.50%)  13/19 (68.42%) 
Nausea * 1  7/11 (63.64%)  5/8 (62.50%)  12/19 (63.16%) 
Vomiting * 1  4/11 (36.36%)  7/8 (87.50%)  11/19 (57.89%) 
Constipation * 1  4/11 (36.36%)  5/8 (62.50%)  9/19 (47.37%) 
Abdominal pain * 1  3/11 (27.27%)  4/8 (50.00%)  7/19 (36.84%) 
Diarrhoea * 1  4/11 (36.36%)  3/8 (37.50%)  7/19 (36.84%) 
Dyspepsia * 1  4/11 (36.36%)  2/8 (25.00%)  6/19 (31.58%) 
Toothache * 1  1/11 (9.09%)  2/8 (25.00%)  3/19 (15.79%) 
Abdominal distension * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Abdominal pain upper * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Gastritis * 1  2/11 (18.18%)  0/8 (0.00%)  2/19 (10.53%) 
Gastrointestinal inflammation * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Gingival bleeding * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Proctalgia * 1  2/11 (18.18%)  0/8 (0.00%)  2/19 (10.53%) 
Anal fissure * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Aphthous ulcer * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Dysphagia * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Haemorrhoids * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Lip swelling * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Oesophagitis * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Paraesthesia oral * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Rectal haemorrhage * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
General disorders       
Catheter site pain * 1  4/11 (36.36%)  5/8 (62.50%)  9/19 (47.37%) 
Fatigue * 1  4/11 (36.36%)  2/8 (25.00%)  6/19 (31.58%) 
Pyrexia * 1  3/11 (27.27%)  2/8 (25.00%)  5/19 (26.32%) 
Non-cardiac chest pain * 1  2/11 (18.18%)  1/8 (12.50%)  3/19 (15.79%) 
Pain * 1  1/11 (9.09%)  2/8 (25.00%)  3/19 (15.79%) 
Chest discomfort * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Catheter site haemorrhage * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Catheter site inflammation * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Cyst * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Drug withdrawal syndrome * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Dysplasia * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Face oedema * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Influenza like illness * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Injection site pain * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Injection site reaction * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Hepatobiliary disorders       
Cholecystitis * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Cholelithiasis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Hepatic congestion * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Hepatomegaly * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Jaundice * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Periportal sinus dilatation * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Venoocclusive liver disease * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Immune system disorders       
Drug hypersensitivity * 1  2/11 (18.18%)  0/8 (0.00%)  2/19 (10.53%) 
Anaphylactic reaction * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Infections and infestations       
Upper respiratory tract infection * 1  0/11 (0.00%)  4/8 (50.00%)  4/19 (21.05%) 
Anal abscess * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Paronychia * 1  2/11 (18.18%)  0/8 (0.00%)  2/19 (10.53%) 
Anorectal infection bacterial * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Bacterial vaginosis * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Bronchitis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Catheter site cellulitis * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Cellulitis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Eye infection * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Folliculitis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Gastroenteritis viral * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Herpes simplex * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Influenza * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Moraxella infection * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Nasopharyngitis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Pharyngitis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Pneumonia * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Pseudomonal bacteraemia * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Rash pustular * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Respiratory tract infection viral * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Sialoadenitis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Staphylococcal infection * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Syphilis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Viral upper respiratory tract infection * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Vulvovaginal mycotic infection * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Injury, poisoning and procedural complications       
Procedural pain * 1  6/11 (54.55%)  4/8 (50.00%)  10/19 (52.63%) 
Transfusion reaction * 1  6/11 (54.55%)  3/8 (37.50%)  9/19 (47.37%) 
Skin abrasion * 1  3/11 (27.27%)  0/8 (0.00%)  3/19 (15.79%) 
Contusion * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Infusion related reaction * 1  2/11 (18.18%)  0/8 (0.00%)  2/19 (10.53%) 
Laceration * 1  2/11 (18.18%)  0/8 (0.00%)  2/19 (10.53%) 
Anaphylactic transfusion reaction * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Citrate toxicity * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Iron overload * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Ligament rupture * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Transfusion-related circulatory overload * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Vascular access complication * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Wound * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Investigations       
Alanine aminotransferase increased * 1  3/11 (27.27%)  1/8 (12.50%)  4/19 (21.05%) 
Aspartate aminotransferase increased * 1  3/11 (27.27%)  0/8 (0.00%)  3/19 (15.79%) 
Blood bilirubin increased * 1  3/11 (27.27%)  0/8 (0.00%)  3/19 (15.79%) 
Gamma-glutamyltransferase increased * 1  1/11 (9.09%)  2/8 (25.00%)  3/19 (15.79%) 
Activated partial thromboplastin time prolonged * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Blood albumin decreased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Blood alkaline phosphatase decreased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Blood creatinine increased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Blood follicle stimulating hormone increased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Blood iron increased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Blood magnesium decreased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Blood potassium decreased * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Blood sodium decreased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
C-reactive protein increased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Carbon dioxide decreased * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Forced expiratory flow decreased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
International normalised ratio increased * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Mean cell haemoglobin concentration increased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Mean cell volume decreased * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Monocyte count decreased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Protein total decreased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Red blood cell count increased * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Reticulocyte count decreased * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Reticulocyte percentage decreased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Weight decreased * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  1/11 (9.09%)  3/8 (37.50%)  4/19 (21.05%) 
Hypokalaemia * 1  2/11 (18.18%)  1/8 (12.50%)  3/19 (15.79%) 
Hypocalcaemia * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Hyponatraemia * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Fluid overload * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Hyperglycaemia * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Hyperphosphataemia * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Hypoalbuminaemia * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Hypomagnesaemia * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Iron overload * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Musculoskeletal and connective tissue disorders       
Back pain * 1  2/11 (18.18%)  2/8 (25.00%)  4/19 (21.05%) 
Bone pain * 1  2/11 (18.18%)  1/8 (12.50%)  3/19 (15.79%) 
Myalgia * 1  1/11 (9.09%)  2/8 (25.00%)  3/19 (15.79%) 
Pain in extremity * 1  1/11 (9.09%)  2/8 (25.00%)  3/19 (15.79%) 
Arthralgia * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Musculoskeletal discomfort * 1  2/11 (18.18%)  0/8 (0.00%)  2/19 (10.53%) 
Neck pain * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Flank pain * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Osteopenia * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Pain in jaw * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Nervous system disorders       
Headache * 1  6/11 (54.55%)  4/8 (50.00%)  10/19 (52.63%) 
Peripheral sensory neuropathy * 1  2/11 (18.18%)  4/8 (50.00%)  6/19 (31.58%) 
Dizziness * 1  1/11 (9.09%)  2/8 (25.00%)  3/19 (15.79%) 
Dysgeusia * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Head discomfort * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Lethargy * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Somnolence * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Psychiatric disorders       
Insomnia * 1  4/11 (36.36%)  2/8 (25.00%)  6/19 (31.58%) 
Agitation * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Anxiety * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Renal and urinary disorders       
Haematuria * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Dysuria * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Urinary retention * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Urinary tract pain * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Reproductive system and breast disorders       
Vaginal haemorrhage * 1  2/11 (18.18%)  4/8 (50.00%)  6/19 (31.58%) 
Menstruation irregular * 1  4/11 (36.36%)  0/8 (0.00%)  4/19 (21.05%) 
Ovarian failure * 1  2/11 (18.18%)  0/8 (0.00%)  2/19 (10.53%) 
Menorrhagia * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Ovarian hyperstimulation syndrome * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Vulvovaginal pruritus * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Respiratory, thoracic and mediastinal disorders       
Epistaxis * 1  6/11 (54.55%)  3/8 (37.50%)  9/19 (47.37%) 
Pharyngeal inflammation * 1  2/11 (18.18%)  5/8 (62.50%)  7/19 (36.84%) 
Cough * 1  1/11 (9.09%)  2/8 (25.00%)  3/19 (15.79%) 
Dyspnoea * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Hypoxia * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Laryngeal pain * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Nasal congestion * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Rales * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Respiratory tract irritation * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Rhinitis allergic * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Throat irritation * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Upper-airway cough syndrome * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1  9/11 (81.82%)  8/8 (100.00%)  17/19 (89.47%) 
Pruritus * 1  2/11 (18.18%)  3/8 (37.50%)  5/19 (26.32%) 
Skin hyperpigmentation * 1  1/11 (9.09%)  3/8 (37.50%)  4/19 (21.05%) 
Urticaria * 1  1/11 (9.09%)  3/8 (37.50%)  4/19 (21.05%) 
Petechiae * 1  1/11 (9.09%)  2/8 (25.00%)  3/19 (15.79%) 
Dermatitis contact * 1  0/11 (0.00%)  2/8 (25.00%)  2/19 (10.53%) 
Dry skin * 1  1/11 (9.09%)  1/8 (12.50%)  2/19 (10.53%) 
Ecchymosis * 1  2/11 (18.18%)  0/8 (0.00%)  2/19 (10.53%) 
Eczema * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Hyperhidrosis * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Pain of skin * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Palpable purpura * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Pruritus allergic * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Pruritus generalised * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Purpura * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Rash * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Rash follicular * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Skin abrasion * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Skin discolouration * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Skin hypopigmentation * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Sweat gland disorder * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Vascular disorders       
Deep vein thrombosis * 1  0/11 (0.00%)  1/8 (12.50%)  1/19 (5.26%) 
Flushing * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Hot flush * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Hypotension * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
Vena cava thrombosis * 1  1/11 (9.09%)  0/8 (0.00%)  1/19 (5.26%) 
1
Term from vocabulary, MedDRA 19.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Study Medical Director
Organization: bluebird bio, Inc.
Phone: 339-499-9300
Responsible Party: bluebird bio
ClinicalTrials.gov Identifier: NCT01745120     History of Changes
Other Study ID Numbers: HGB-204
First Submitted: December 6, 2012
First Posted: December 7, 2012
Results First Submitted: February 7, 2019
Results First Posted: May 8, 2019
Last Update Posted: May 8, 2019