Trial Outcomes & Findings for A Study Evaluating the Safety and Efficacy of the LentiGlobin BB305 Drug Product in β-Thalassemia Major Participants (NCT NCT01745120)

Last Updated: 2019-05-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

19 participants

Primary outcome timeframe

Month 18 to Month 24

Results posted on

2019-05-08

Participant Flow

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).

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.

Participant milestones

Participant milestones
Measure	Non-β0/β0 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).	β0/β0 Participants who were bi-allelic for mutations in the HBB gene that results in absence of expression of β-globin: β0 (β0/β0 genotype) underwent HSC mobilization with G-CSF and plerixafor, followed by myeloablative conditioning and infusion with LentiGlobin BB305 Drug Product at a dose of \>= 3.0 × 10\^6 CD34+ cells/kg.
Overall Study STARTED	11	8
Overall Study COMPLETED	10	8
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Non-β0/β0 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).	β0/β0 Participants who were bi-allelic for mutations in the HBB gene that results in absence of expression of β-globin: β0 (β0/β0 genotype) underwent HSC mobilization with G-CSF and plerixafor, followed by myeloablative conditioning and infusion with LentiGlobin BB305 Drug Product at a dose of \>= 3.0 × 10\^6 CD34+ cells/kg.
Overall Study Investigator decision	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Non-β0/β0 n=11 Participants 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.	β0/β0 n=8 Participants 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 n=19 Participants Total of all reporting groups
Age, Continuous	22.7 Years STANDARD_DEVIATION 6.50 • n=5 Participants	24.1 Years STANDARD_DEVIATION 7.62 • n=7 Participants	23.3 Years STANDARD_DEVIATION 6.82 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian/Italian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 18 to Month 24

Population: Transplant Population (TP) included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.

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.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=10 Participants 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.	β0/β0 n=8 Participants 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.	Overall n=18 Participants 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.
Percentage of Participants With Sustained Production of >=2.0 Grams Per Deciliter (g/dL) of Hemoglobin A (HbA) Containing βA-T87Q-globin (HbAT87Q) for the Six Months Between Month 18 and Month 24	90.0 Percentage of participants	87.5 Percentage of participants	88.9 Percentage of participants

PRIMARY outcome

Timeframe: From time of drug product infusion up to 24 months

Population: TP included all participants in the ITT population (participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor) who underwent LentiGlobin BB305 Drug Product infusion.

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.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=10 Participants 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.	β0/β0 n=8 Participants 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.	Overall n=18 Participants 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.
Percentage of Participants Who Achieved Transfusion Independence (TI)	80.0 Percentage of participants	12.5 Percentage of participants	50.0 Percentage of participants

SECONDARY outcome

Timeframe: Month 18, Month 24

TI was defined as a weighted average Hb \>= 9 g/dL without any pRBC transfusions for a continuous period of \>= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=10 Participants 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.	β0/β0 n=8 Participants 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.	Overall n=18 Participants 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.
Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24 Month 18	80.0 Percentage of participants	12.5 Percentage of participants	50.0 Percentage of participants
Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24 Month 24	80.0 Percentage of participants	0 Percentage of participants	44.4 Percentage of participants

SECONDARY outcome

Timeframe: From time of drug product infusion up to 24 months

TI was defined as a weighted average Hb \>= 9 g/dL without any pRBC transfusions for a continuous period of \>= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Time period of TI will start when participants achieve a Hb \>= 9 g/dL with no transfusions in the preceding 60 days. Duration of TI was calculated as the time from the start of TI (i.e. first Hb \>= 9 g/dL with no transfusions in the preceding 60 days) up to the last available Hb at which the TI criteria are still met.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=8 Participants 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.	β0/β0 n=1 Participants 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.	Overall n=9 Participants 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.
Duration of Transfusion Independence (TI)	18.91 Months Interval 15.2 to 21.4	16.13 Months Interval 16.13 to 16.13	17.28 Months Interval 15.2 to 21.4

SECONDARY outcome

Timeframe: From time of drug product infusion up to 24 months

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=8 Participants 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.	β0/β0 n=1 Participants 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.	Overall n=9 Participants 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.
Time From LentiGlobin BB305 Drug Product Infusion to Last pRBC Transfusion Prior to Achieving Transfusion Independence (TI)	2.00 Months Interval 0.3 to 5.8	1.81 Months Interval 1.81 to 1.81	1.81 Months Interval 0.3 to 5.8

SECONDARY outcome

Timeframe: From time of drug product infusion up to 24 months

TI was defined as a weighted average Hb \>= 9 g/dL without any pRBC transfusions for a continuous period of \>= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Time from drug product infusion to initial achievement of TI was calculated as the time from drug product infusion to the first Hb at which a participant can be declared as TI.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=8 Participants 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.	β0/β0 n=1 Participants 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.	Overall n=9 Participants 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.
Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI)	17.12 Months Interval 15.0 to 20.9	17.51 Months Interval 17.51 to 17.51	17.51 Months Interval 15.0 to 20.9

SECONDARY outcome

Timeframe: From time of drug product infusion up to 24 months

The weighted average Hb is an average area under the curve during the period of TI, from the start of TI when the Hb is first \>= 9 g/dL with no transfusions in the preceding 60 days to the last available Hb at which the TI criteria are still met. TI was defined as a weighted average Hb \>= 9 g/dL without any pRBC transfusions for a continuous period of \>= 12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Weighted average Hb during the period of TI was reported.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=8 Participants 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.	β0/β0 n=1 Participants 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.	Overall n=9 Participants 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.
Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI)	10.44 Grams per deciliter (g/dL) Standard Deviation 1.277	10.11 Grams per deciliter (g/dL) Standard Deviation NA Standard deviation was not calculated due to less number of participants.	10.41 Grams per deciliter (g/dL) Standard Deviation 1.200

SECONDARY outcome

Timeframe: Baseline, Month 24

The annualized number of pRBC transfusions over the 2 year period prior to drug product infusion was compared to the annualized number of pRBC transfusions during the Month 6 to Month 24 period post drug product infusion and the percentage change was reported.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=10 Participants 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.	β0/β0 n=8 Participants 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.	Overall n=18 Participants 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.
Percentage Change From Baseline in Annualized Number of Packed Red Blood Cells (pRBC) Transfusions at Month 24	-100.00 Percentage of annualized transfusions Interval -100.0 to -20.7	-65.80 Percentage of annualized transfusions Interval -96.2 to 2.5	-90.74 Percentage of annualized transfusions Interval -100.0 to 2.5

SECONDARY outcome

Timeframe: Baseline, Month 24

The annualized volume of pRBC transfusions over the 2 year period prior to drug product infusion was compared to the annualized volume of pRBC transfusions in the Month 6 to Month 24 period post drug product Infusion and the percentage change from baseline was reported.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=10 Participants 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.	β0/β0 n=8 Participants 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.	Overall n=18 Participants 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.
Percentage Change From Baseline in Average Annual Packed Red Blood Cells (pRBC) Transfusion Volume at Month 24	-100.00 Percentage of pRBC transfusion volume Interval -100.0 to -26.8	-71.97 Percentage of pRBC transfusion volume Interval -97.8 to -8.3	-92.38 Percentage of pRBC transfusion volume Interval -100.0 to -8.3

SECONDARY outcome

Timeframe: Baseline, Month 6 to Month 24

Weighted average Hb nadir was defined as an average area under the curve where the Hb closest but within 3 days prior to a transfusion is used as the Hb nadir. If there is a period of more than 60 days without a pRBC transfusion, all Hb records between Day 61 and day of last visit or next transfusion (inclusive) were also considered as nadirs. The weighted average nadir Hb during the period of Month 6 to Month 24 was compared to the weighted average nadir Hb during the 2 years prior to enrollment.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=10 Participants 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.	β0/β0 n=8 Participants 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.	Overall n=18 Participants 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.
Weighted Average Nadir Hemoglobin (Hb) Baseline	8.73 Grams per deciliter (g/dL) Standard Deviation 1.014	9.38 Grams per deciliter (g/dL) Standard Deviation 0.431	9.02 Grams per deciliter (g/dL) Standard Deviation 0.855
Weighted Average Nadir Hemoglobin (Hb) Month 6 to Month 24	9.97 Grams per deciliter (g/dL) Standard Deviation 1.678	8.67 Grams per deciliter (g/dL) Standard Deviation 0.617	9.39 Grams per deciliter (g/dL) Standard Deviation 1.446

SECONDARY outcome

Timeframe: From time of drug product infusion up to 24 months

Neutrophil engraftment was defined as achieving 3 consecutive absolute neutrophil count (ANC) \>= 0.5 × 10\^9/L on different days after a post-transplant value of \< 0.5 × 10\^9/L within 42 days after drug product infusion.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=10 Participants 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.	β0/β0 n=8 Participants 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.	Overall n=18 Participants 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.
Number of Participants With Successful Neutrophil Engraftment	10 Participants	8 Participants	18 Participants

SECONDARY outcome

Timeframe: From time of drug product infusion up to 24 months

Population: TP included all participants in the ITT population who underwent LentiGlobin BB305 Drug Product infusion.

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.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=10 Participants 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.	β0/β0 n=8 Participants 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.	Overall n=18 Participants 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.
Time to Neutrophil Engraftment	18.5 Days Interval 14.0 to 27.0	19.5 Days Interval 15.0 to 30.0	18.5 Days Interval 14.0 to 30.0

SECONDARY outcome

Timeframe: From time of drug product infusion up to 24 months

Platelet engraftment was defined as achieving 3 consecutive platelet values \>= 20 × 10\^9/L on different days after a post-transplant value of \< 20 × 10\^9/L, while no platelet transfusions administered for 7 days immediately preceding and during the evaluation period.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=10 Participants 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.	β0/β0 n=8 Participants 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.	Overall n=18 Participants 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.
Number of Participants With Successful Platelet Engraftment	10 Participants	8 Participants	18 Participants

SECONDARY outcome

Timeframe: From time of drug product infusion up to 24 months

Time to platelet engraftment was defined as achieving of first 3 consecutive platelet values \>= 20 × 10\^9/L obtained on different days after a post-transplant value of \< 20 × 10\^9/L, while no platelet transfusions administered for 7 days immediately preceding and during the evaluation period. The day of platelet engraftment is the first day of the 3 consecutive measurements, where Day 1 is the day of drug product infusion.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=10 Participants 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.	β0/β0 n=8 Participants 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.	Overall n=18 Participants 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.
Time to Platelet Engraftment	50.5 Days Interval 19.0 to 191.0	36.0 Days Interval 31.0 to 55.0	39.5 Days Interval 19.0 to 191.0

SECONDARY outcome

Timeframe: Through 100 and 365 days post-LentiGlobin BB305 Drug Product infusion

Population: ITT population included all participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor.

Transplant-related mortality was determined by the investigator (any deaths considered related to the transplant.)

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=19 Participants 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.	β0/β0 Participants who were bi-allelic for mutations in the HBB gene that results in absence of expression of β-globin: β0 (β0/β0 genotype) underwent HSC mobilization with G-CSF and plerixafor, followed by myeloablative conditioning and infusion with LentiGlobin BB305 Drug Product at a dose of \>= 3.0 × 10\^6 CD34+ cells/kg.	Overall 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.
Transplant-related Mortality	0 Participants	—	—

SECONDARY outcome

Timeframe: From time of drug product infusion up to 24 months

Population: ITT population included all participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor.

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.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=19 Participants 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.	β0/β0 Participants who were bi-allelic for mutations in the HBB gene that results in absence of expression of β-globin: β0 (β0/β0 genotype) underwent HSC mobilization with G-CSF and plerixafor, followed by myeloablative conditioning and infusion with LentiGlobin BB305 Drug Product at a dose of \>= 3.0 × 10\^6 CD34+ cells/kg.	Overall 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 Survival	100 Percentage of participants	—	—

SECONDARY outcome

Timeframe: From time of drug product infusion up to 24 months

Blood samples were analyzed for detection of RCL using RCL co-culture assay.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=18 Participants 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.	β0/β0 Participants who were bi-allelic for mutations in the HBB gene that results in absence of expression of β-globin: β0 (β0/β0 genotype) underwent HSC mobilization with G-CSF and plerixafor, followed by myeloablative conditioning and infusion with LentiGlobin BB305 Drug Product at a dose of \>= 3.0 × 10\^6 CD34+ cells/kg.	Overall 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.
Percentage of Participants Detected With Replication-competent Lentivirus (RCL)	0 Percentage of participants	—	—

SECONDARY outcome

Timeframe: From time of drug product infusion up to 24 months

Linear amplification-mediated polymerase chain reaction (LAM-PCR) coupled with next generation sequencing and subsequent (semi-) automated data mining allowed high-throughput analysis of vector integration site (IS) in blood cells from treated participants at multiple time points. ISs detected in peripheral blood cells at early time points generally were due to the expansion of transduced short-term progenitor stem cell clones, and gradually shift to include sites detected due to expansion of transduced long-term stem cell clones. An efficient transduction procedure was anticipated to give rise to a polyclonal population in the participant, reflected by the detection of multiple IS. Additionally, ISA allowed monitoring of the relative contribution of individual clones over time. Number of participants who had IS that contributed to \>=30% of the total clones at any time was used as a first step to investigating whether clonal dominance was achieved.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=18 Participants 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.	β0/β0 Participants who were bi-allelic for mutations in the HBB gene that results in absence of expression of β-globin: β0 (β0/β0 genotype) underwent HSC mobilization with G-CSF and plerixafor, followed by myeloablative conditioning and infusion with LentiGlobin BB305 Drug Product at a dose of \>= 3.0 × 10\^6 CD34+ cells/kg.	Overall 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.
Number of Participants With Integration Site Analysis (ISA) With >30% Clonal Contribution Yes	0 Participants	—	—
Number of Participants With Integration Site Analysis (ISA) With >30% Clonal Contribution No	18 Participants	—	—

SECONDARY outcome

Timeframe: From signing of informed consent to 24 months after the drug product infusion

Population: ITT population included all participants who initiated any study procedures, beginning with mobilization by G-CSF with or without plerixafor.

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.

Outcome measures

Outcome measures
Measure	Non-β0/β0 n=11 Participants 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.	β0/β0 n=8 Participants 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.	Overall n=19 Participants 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.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Adverse Events	10 Participants	8 Participants	18 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious Adverse Events	6 Participants	4 Participants	10 Participants

Adverse Events

Non-β0/β0

Serious events: 6 serious events

Other events: 10 other events

Deaths: 0 deaths

β0/β0

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

Overall

Serious events: 10 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Non-β0/β0 n=11 participants at risk 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.	β0/β0 n=8 participants at risk 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.	Overall n=19 participants at risk 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.
Blood and lymphatic system disorders Anaemia	0.00% 0/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	12.5% 1/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Cardiac disorders Intracardiac thrombus	0.00% 0/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	12.5% 1/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Hepatobiliary disorders Venoocclusive liver disease	9.1% 1/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	12.5% 1/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	10.5% 2/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Infections and infestations Appendicitis	9.1% 1/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	0.00% 0/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Infections and infestations Asymptomatic HIV infection	9.1% 1/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	0.00% 0/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Infections and infestations Cat scratch disease	0.00% 0/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	12.5% 1/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Infections and infestations Catheter site infection	0.00% 0/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	12.5% 1/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Infections and infestations Cellulitis	0.00% 0/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	12.5% 1/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Infections and infestations Diarrhoea infectious	9.1% 1/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	0.00% 0/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Infections and infestations Gastroenteritis	9.1% 1/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	0.00% 0/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Infections and infestations Viral infection	9.1% 1/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	0.00% 0/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Injury, poisoning and procedural complications Post procedural haemorrhage	9.1% 1/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	0.00% 0/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	12.5% 1/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.
Vascular disorders Vena cava thrombosis	9.1% 1/11 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	0.00% 0/8 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.	5.3% 1/19 • From signing of informed consent to 24 months after the drug product infusion ITT population included all participants who initiated any study procedures, beginning with mobilization by GCSF with or without plerixafor.

Other adverse events

Additional Information

Study Medical Director

bluebird bio, Inc.

Phone: 339-499-9300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60