Beta-Thalassemia
Conditions
Brief summary
This is a single-arm, multi-site, single-dose, Phase 3 study in approximately 18 participants less than or equal to (\<=) 50 years of age with transfusion-dependent β-thalassemia (TDT), who have a β0/β0, β0/IVS-I-110, or IVS-I-110/IVS-I-110 genotype. The study will evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product.
Interventions
LentiGlobin BB305 Drug Product is administered by IV infusion following myeloablative conditioning with busulfan.
Sponsors
Genetix Biotherapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
• Participants less than or equal to (\<=) 50 years of age at the time of consent or assent (as applicable), and able to provide written consent (adults, or legal guardians, as applicable) or assent (adolescents or children). Provided that the data monitoring committee (DMC) has approved enrolling participants younger than 5 years of age, participants younger than 5 years of age may be enrolled if they weigh a minimum of 6 kilograms (kg) and are reasonably anticipated to be able to provide at least the minimum number of cells required to initiate the manufacturing process. * Diagnosis of TDT with a history of at least 100 milliliter per kilogram per year (mL/kg/year) of pRBCs in the 2 years preceding enrollment (all participants), or be managed under standard thalassemia guidelines with \>= 8 transfusions of pRBCs per year in the 2 years preceding enrollment (participants \>=12 years). * Clinically stable and eligible to undergo HSCT. * Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.
Exclusion criteria
* Presence of a mutation characterized as other then β0 (e.g., β+, βE, βC) on at least one β-globin gene (HBB) allele. * Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2), hepatitis B virus (HBV), or hepatitis C (HCV). * A white blood cell (WBC) count less than (\<) 3×10\^9/liter (L), and/or platelet count \<100×10\^9/L not related to hypersplenism. * Uncorrected bleeding disorder. * Any prior or current malignancy. * Prior HSCT. * Advanced liver disease. * A cardiac T2\* \<10 ms by MRI. * Any other evidence of severe iron overload that, in the investigator's opinion, warrants exclusion. * Participation in another clinical study with an investigational drug within 30 days of Screening. * Any other condition that would render the participant ineligible for HSCT, as determined by the attending transplant physician or investigator. * Prior receipt of gene therapy. * Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile participant. * A known and available human leukocyte antigen (HLA) matched family donor. * Any contraindications to the use of granulocyte colony stimulating factor (G-CSF) and plerixafor during the mobilization of hematopoietic stem cells and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Have Achieved Transfusion Independence (TI) | From 12 to 24 months post-transplant | TI was defined as a weighted average hemoglobin (Hb) \>= 9 grams per deciliter (g/dL) without any packed red blood cell (pRBC) transfusions for a continuous period of \>= 12 months at any time during the study after drug product infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Have Achieved Transfusion Independence (TI) at Month 24 | At Month 24 post-transplant | TI was defined as a weighted average hemoglobin (Hb) \>= 9 grams per deciliter (g/dL) without any packed red blood cell (pRBC) transfusions for a continuous period of \>= 12 months at any time during the study after drug product infusion. |
| Duration of Transfusion Independence (TI) | From start of TI up to Month 24 (actual maximum time frame of up to approximately 25 months due to visit window) | Duration of TI was calculated as the time from the start of TI (i.e. first Hb \>=9 with no transfusions in the preceding 60 days) up to the last available Hb at which the TI criteria are still met using Kaplan-Meier methodology. |
| Time From Drug Product Infusion to Achievement of Transfusion Independence (TI) | From drug product infusion to start of TI (up to Month 24 [actual maximum time frame of up to approximately 25 months due to visit window]) | Time from drug product infusion to achievement of TI was calculated as the time from drug product infusion to the first hemoglobin at which a participant can be declared as TI (that is to 'start of TI + \>= 12 months', dependent on Hb lab schedule). |
| Weighted Average Hemoglobin (Hb) During Transfusion Independence (TI) | Timeframe varied by subject. For a given subject, the endpoint was calculated from 60 days after the last pRBC transfusion (so transfused blood did not confound the weighted average calculation) through the Month 24 Visit for that subject. | Weighted average Hb was defined as the weighted average of Hb values without any pRBC transfusions in the proceeding 60 days for a given subject. Ratio of the time between two Hb values and the time between the first and the last Hb values was used as the weight for calculation. |
| Percentage of Participants Who Meet the Definition of Transfusion Reduction (TR) | From 12 to 24 months post-transplant | TR was defined as demonstration of a 60 percent (%) reduction in the annualized volume of pRBC transfusion requirements (in milliliter per kilogram \[mL/kg\]) in the post-treatment time period from 12 Months post-drug product infusion through Month 24 compared to the annualized mL/kg pRBC transfusion requirement during the 24 months prior to study enrollment. |
| Percentage of Participants Who Had a Reduction of At Least 50%, 60%, 75%, 90% or 100% in the Annualized pRBCs Transfusion Volume | 12 months post-drug product infusion through Month 24 | Percentage of participants with a reduction in the annualized mL/kg pRBCs transfused from 12 months post-drug product infusion through Month 24 (approximately a 12-month period) of at least 50%, 60%, 75%, 90% or 100% compared to the annualized mL/kg pRBC transfusion requirement during the 24 months prior to enrollment. |
| Annualized Number of pRBC Transfusions | From 12 months post-drug product infusion through Month 24 | Annualized number of pRBC transfusions from 12 months post-drug product infusion through Month 24 was reported. |
| Annualized Volume of pRBC Transfusions | From 12 to 24 months post-transplant | Annualized volume of pRBC transfusions from 12 months post-drug product infusion through Month 24 compared to the annualized volume of transfusions during the 24 months prior to enrollment. |
| Time From Drug Product Infusion to Last pRBC Transfusion | From start of drug product infusion up to Month 24 | Time from drug product infusion to last pRBC transfusion was reported. |
| Time From Last pRBC Transfusion to 24 Months | From last pRBC Transfusion up to Month 24 (actual maximum time frame of up to approximately 27 months due to visit window) | Time From Last pRBC Transfusion to the Month 24 was reported. |
| Weighted Average Nadir Hemoglobin (Hb) | 12 months post-drug product infusion through Month 24 | The weighted average nadir Hb was defined as the most recent Hb prior to each pRBC transfusion, on the day of transfusion or within 3 days and, if there was a period of more than 60 days without transfusion, all Hb records between Day 61 and last follow-up or next transfusion (inclusive) was included. The weighted average nadir Hb during the period of 12 months post-drug product infusion to Month 24 was compared to the weighted average nadir Hb during the 24 months prior to enrollment. |
| Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24 | At Month 6, 9, 12, 18 and 24 | Unsupported total Hb level was defined as the total Hb measurement level without any acute or chronic pRBC transfusions within 60 days prior to the measurement date. |
| Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Months 6, 9, 12, 18 and 24 | Number of participants with unsupported total Hb levels (\>=10 g/dL, \>=11 g/dL, \>=12 g/dL, \>=13 g/dL, and \>=14 g/dL) meeting the thresholds were reported at Months 6, 9, 12, 18 and 24. Participants were evaluable if they had an unsupported total Hb measurement at the specific timepoint, where unsupported total Hb level is defined as the total Hb measurement level without any acute or chronic pRBC transfusions within 60 days prior to the measurement date. |
| Percentage of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion | From 6 to 24 months | Percentage of participants who have not received chelation therapy for at least 6 months following drug product infusion were reported. |
| Time From Last Iron Chelation Use to Last Follow-up | From last Iron Chelation up to Month 24 (actual maximum time frame of up to approximately 29 months due to visit window) | Time from last iron chelation use to last follow-up to 24 months was reported. |
| Number of Participants Who Used Therapeutic Phlebotomy Post Drug Product Infusion | From drug product infusion through Month 24 | Therapeutic phlebotomy could be used in lieu of chelation in participants who had Hb consistently \>= 11 g/dL and who were no longer receiving regular transfusions, at the discretion of the investigator. Number of participants who used therapeutic phlebotomy post Drug Product infusion for up to Month 24 were reported. |
| Annualized Phlebotomy Therapy Usage Following Drug Product Infusion | From drug product infusion through Month 24 | Annualized phlebotomy therapy usage (number of procedures per year, calculated from DP infusion through last follow-up) were reported. |
| Change From Baseline in Liver Iron Content by Magnetic Resonance Imaging (MRI) | Baseline, Month 12 and 24 | Change From Baseline in Liver Iron Content by MRI at Months 12 and 24 were reported. Baseline is defined as value closest to but prior to conditioning. |
| Change From Baseline in Cardiac T2* on MRI | Baseline, Months 12 and 24 | Change From Baseline in Cardiac T2\* on MRI from Baseline, Month 12 and 24 was reported. |
| Change From Baseline in Serum Ferritin | Baseline, Month 12 and 24 | Serum ferritin was commonly used for an indirect estimation of body iron stores. Although sensitive, it is not specific for iron overload as it can be elevated in a variety of infectious and inflammatory states, and in the presence of cytolysis. Change from baseline in serum ferritin at Months 12 and 24 was reported. |
| Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Scores at Months 12 and 24 | Baseline, Month 12 and 24 | PedsQL GCS designed to measure health-related quality of life in pediatric and adolescents (2-18 years). It encompassed 4 dimensions of functioning (physical \[8 items\], emotional \[5 items\], social \[5 items\], school \[3 items\]). Age groups: Toddler (2-4 years), Young pediatric (5-7 years), Pediatric (8-12 years), Teens (13-18 years). The questionnaire was also completed by parent/caregiver to assess parents' perceptions of their children's quality of life. The Toddler group consisted of 21 items, using a 5-point Likert scale (0 to 4); all other groups consisted of 23 items, with a 3-point Likert scale (0, 2, 4) for young pediatric, a 5-point Likert scale for pediatric and teens groups. All reported scores were transformed on a scale from 0 to 100 for each domain where 0=100, 1=75, 2=50, 3=25, and 4=0. Higher scores correspond with higher quality of life. |
| Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y) VAS Health Status at Months 12 and 24 | Baseline, Months 12 and 24 | EQ-5D is a validated, standardized, generic instrument that was most widely used preference based health related quality of life questionnaire in cost effectiveness and health technologies assessment. EQ-5D-Y was a version of instrument specifically developed and validated for use by youths aged 12 through 17 years. The EQ-5D-Y visual analog scale (VAS) consisted of a 20-cm vertical VAS, with anchors of 0 (worst imaginable health state) and 100 (best imaginable health state). Respondents were asked to rate their own health state today by drawing a line from a box containing these words to the point on the scale that they felt most accurately reflected their current health state. The VAS was reported (raw data) on a scale of 0-100 where 0= death and 100= perfect health. Higher scores corresponded with higher quality of life. |
| Change From Baseline in EuroQol Quality of Life 5-Dimension Adult Scale (EQ-5D-3L) VAS Heath Status Score at Months 12 and 24 | Baseline, Months 12 and 24 | EQ-5D is a validated, standardized, generic instrument that was most widely used preference based health related quality of life (HRQoL) questionnaire in cost effectiveness and health technologies assessment. Participants age \>=18 at time of informed consent were eligible to complete the EQ-5D-3L visual analog scale (VAS) which consisted of a 20-cm vertical VAS, with anchors of 0 (worst imaginable health state) and 100 (best imaginable health state). Respondents were asked to rate their own health state today by drawing a line from a box containing these words to the point on the scale that they felt most accurately reflected their current health state. The VAS was reported (raw data) on a scale of 0-100 where 0= death and 100= perfect health. Negative change in score indicated decrease in quality of life (as measured by EQ5D VAS) from baseline. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Total Score | Baseline, Months 12 and 24 | FACT-BMT is assessed bone marrow transplant related quality of life in adults. Total score was sum of sub-scale scores for 5 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, and Bone Marrow Transplantation Subscale. Each item scored on a 5-point Likert scale based on participant agreement with each statement: 0 for not at all, 1 for a little bit, 2 for somewhat, 3 for quite a bit, and 4 for very much. Reported scores were transformed as follows: After taking into account reverse scores for questions constructed in negative form, subscale score for each domain was calculated by multiplying sum of item scores by number of items in subscale, then dividing by number of items answered. Total score was sum of subscale total added together and ranges from 0-148. Higher scores corresponded with higher quality of life. |
| Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Months 12 and 24 | Baseline, Months 12 and 24 | SF-36 was designed to measure health-related quality of life in adults. The instrument consisted of 36 items that were aggregated into 8 multi-item scales (physical functioning \[1=yes, limited a lot, to 3=no, not limited at all\], role-physical \[1=all of time, to 5=none of time\], bodily pain \[1=very severe, to 6=none\], general health \[1=poor, to 5=excellent\], vitality \[1=none of time, to 5=all of time\], social functioning \[1=all of time, to 5=none of time\], role emotional \[1=all of time, to 5=none of time\] and mental health \[1=all of time, to 5=none of the time\]). The 8 scales were summarized as Physical Component Summary (PCS) score (physical functioning, role-physical, bodily pain, general health scales) and Mental Component Summary (MCS) score (vitality, social functioning, role-emotional, mental health scales). Reported summary scores were transformed on a scale from 0-100 (higher scores corresponded with higher quality of life), with change from baseline results being presented. |
Countries
France, Germany, Greece, Italy, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 9 study centers in France, Germany, Greece, Italy, United Kingdom, and United States, of which 8 active centers had enrolled participants from 08 June 2017 to 15 November 2022.
Pre-assignment details
A total of 19 participants were enrolled, of which 18 participants aged \<=50 years were treated with LentiGlobin BB305 Drug Product.
Participants by arm
| Arm | Count |
|---|---|
| LentiGlobin BB305 Drug Product Participants \<=50 years of age received a single IV infusion of LentiGlobin BB305 Drug Product at a dose of \>=5.0 × 10\^6 CD34+ cells/kg body weight on Day 1 after myeloablative conditioning with busulfan (4 days of conditioning followed by at least 48 hours of washout) (termed the Transplant population). | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrew consent prior to conditioning | 1 |
Baseline characteristics
| Characteristic | LentiGlobin BB305 Drug Product |
|---|---|
| Age, Continuous | 14.8 Years STANDARD_DEVIATION 8.77 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 19 / 19 |
| serious Total, serious adverse events | 6 / 19 |
Outcome results
Primary
Percentage of Participants Who Have Achieved Transfusion Independence (TI)
TI was defined as a weighted average hemoglobin (Hb) \>= 9 grams per deciliter (g/dL) without any packed red blood cell (pRBC) transfusions for a continuous period of \>= 12 months at any time during the study after drug product infusion.
Time frame: From 12 to 24 months post-transplant
Population: TP included all participants who received beti-cel. Participant evaluable for TI are defined as participant who have achieved TI, have not achieved TI in their parent study, or completed their parent study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Percentage of Participants Who Have Achieved Transfusion Independence (TI) | 88.9 Percentage of participants |
Secondary
Annualized Number of pRBC Transfusions
Annualized number of pRBC transfusions from 12 months post-drug product infusion through Month 24 was reported.
Time frame: From 12 months post-drug product infusion through Month 24
Population: TP included all participants who received beti-cel.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LentiGlobin BB305 Drug Product | Annualized Number of pRBC Transfusions | 0.68 pRBC transfusions per year | Standard Deviation 2.701 |
Secondary
Annualized Phlebotomy Therapy Usage Following Drug Product Infusion
Annualized phlebotomy therapy usage (number of procedures per year, calculated from DP infusion through last follow-up) were reported.
Time frame: From drug product infusion through Month 24
Population: TP included all participants who received beti-cel. Here, Overall number of participants analyzed signifies those participants who received therapeutic phlebotomy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LentiGlobin BB305 Drug Product | Annualized Phlebotomy Therapy Usage Following Drug Product Infusion | 4.22 Number of procedures per year | Standard Deviation 3.192 |
Secondary
Annualized Volume of pRBC Transfusions
Annualized volume of pRBC transfusions from 12 months post-drug product infusion through Month 24 compared to the annualized volume of transfusions during the 24 months prior to enrollment.
Time frame: From 12 to 24 months post-transplant
Population: TP included all participants who received beti-cel.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LentiGlobin BB305 Drug Product | Annualized Volume of pRBC Transfusions | 11.589 milliliter/kilogram/year (mL/kg/year) | Standard Deviation 47.408 |
Secondary
Change From Baseline in Cardiac T2* on MRI
Change From Baseline in Cardiac T2\* on MRI from Baseline, Month 12 and 24 was reported.
Time frame: Baseline, Months 12 and 24
Population: TP included all participants who received beti-cel. Participants were evaluable for TI if they had completed the study (i.e., completed the Month 24 Visit), achieved TI, or did not achieve TI during the study. Here, number analyzed signifies those participants who were evaluable at specific timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LentiGlobin BB305 Drug Product | Change From Baseline in Cardiac T2* on MRI | Change at Month 12 | -0.2 milliseconds |
| LentiGlobin BB305 Drug Product | Change From Baseline in Cardiac T2* on MRI | Change at Month 24 | 0.2 milliseconds |
Secondary
Change From Baseline in EuroQol Quality of Life 5-Dimension Adult Scale (EQ-5D-3L) VAS Heath Status Score at Months 12 and 24
EQ-5D is a validated, standardized, generic instrument that was most widely used preference based health related quality of life (HRQoL) questionnaire in cost effectiveness and health technologies assessment. Participants age \>=18 at time of informed consent were eligible to complete the EQ-5D-3L visual analog scale (VAS) which consisted of a 20-cm vertical VAS, with anchors of 0 (worst imaginable health state) and 100 (best imaginable health state). Respondents were asked to rate their own health state today by drawing a line from a box containing these words to the point on the scale that they felt most accurately reflected their current health state. The VAS was reported (raw data) on a scale of 0-100 where 0= death and 100= perfect health. Negative change in score indicated decrease in quality of life (as measured by EQ5D VAS) from baseline.
Time frame: Baseline, Months 12 and 24
Population: TP included all participants who received beti-cel. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LentiGlobin BB305 Drug Product | Change From Baseline in EuroQol Quality of Life 5-Dimension Adult Scale (EQ-5D-3L) VAS Heath Status Score at Months 12 and 24 | Health State: Change at Month 12 | -3.6 Score on a scale | Standard Deviation 13.13 |
| LentiGlobin BB305 Drug Product | Change From Baseline in EuroQol Quality of Life 5-Dimension Adult Scale (EQ-5D-3L) VAS Heath Status Score at Months 12 and 24 | Health State: Change at Month 24 | -2.4 Score on a scale | Standard Deviation 10.5 |
Secondary
Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y) VAS Health Status at Months 12 and 24
EQ-5D is a validated, standardized, generic instrument that was most widely used preference based health related quality of life questionnaire in cost effectiveness and health technologies assessment. EQ-5D-Y was a version of instrument specifically developed and validated for use by youths aged 12 through 17 years. The EQ-5D-Y visual analog scale (VAS) consisted of a 20-cm vertical VAS, with anchors of 0 (worst imaginable health state) and 100 (best imaginable health state). Respondents were asked to rate their own health state today by drawing a line from a box containing these words to the point on the scale that they felt most accurately reflected their current health state. The VAS was reported (raw data) on a scale of 0-100 where 0= death and 100= perfect health. Higher scores corresponded with higher quality of life.
Time frame: Baseline, Months 12 and 24
Population: TP included all participants who received beti-cel. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LentiGlobin BB305 Drug Product | Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y) VAS Health Status at Months 12 and 24 | Health State: Change at Month 12 | 0.3 Score on a scale | Standard Deviation 11.91 |
| LentiGlobin BB305 Drug Product | Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y) VAS Health Status at Months 12 and 24 | Health State: Change at Month 24 | 2.0 Score on a scale | Standard Deviation 12.33 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Total Score
FACT-BMT is assessed bone marrow transplant related quality of life in adults. Total score was sum of sub-scale scores for 5 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, and Bone Marrow Transplantation Subscale. Each item scored on a 5-point Likert scale based on participant agreement with each statement: 0 for not at all, 1 for a little bit, 2 for somewhat, 3 for quite a bit, and 4 for very much. Reported scores were transformed as follows: After taking into account reverse scores for questions constructed in negative form, subscale score for each domain was calculated by multiplying sum of item scores by number of items in subscale, then dividing by number of items answered. Total score was sum of subscale total added together and ranges from 0-148. Higher scores corresponded with higher quality of life.
Time frame: Baseline, Months 12 and 24
Population: TP included all participants who received beti-cel. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LentiGlobin BB305 Drug Product | Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Total Score | Total Score: Change at Month 12 | 0.33 Score on a scale | Standard Deviation 6.716 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Total Score | Total Score: Change at Month 24 | 2.58 Score on a scale | Standard Deviation 4.246 |
Secondary
Change From Baseline in Liver Iron Content by Magnetic Resonance Imaging (MRI)
Change From Baseline in Liver Iron Content by MRI at Months 12 and 24 were reported. Baseline is defined as value closest to but prior to conditioning.
Time frame: Baseline, Month 12 and 24
Population: TP included all participants who received beti-cel. Participants were evaluable for TI if they had completed the study (i.e., completed the Month 24 Visit), achieved TI, or did not achieve TI during the study. Here, number analyzed signifies those participants who had LIC data available at Baseline, Months 12 and 24.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LentiGlobin BB305 Drug Product | Change From Baseline in Liver Iron Content by Magnetic Resonance Imaging (MRI) | Change at Month 12 | 3.171 milligram per gram (mg/g) | Standard Deviation 5.4134 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Liver Iron Content by Magnetic Resonance Imaging (MRI) | Change at Month 24 | 1.033 milligram per gram (mg/g) | Standard Deviation 4.4407 |
Secondary
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Scores at Months 12 and 24
PedsQL GCS designed to measure health-related quality of life in pediatric and adolescents (2-18 years). It encompassed 4 dimensions of functioning (physical \[8 items\], emotional \[5 items\], social \[5 items\], school \[3 items\]). Age groups: Toddler (2-4 years), Young pediatric (5-7 years), Pediatric (8-12 years), Teens (13-18 years). The questionnaire was also completed by parent/caregiver to assess parents' perceptions of their children's quality of life. The Toddler group consisted of 21 items, using a 5-point Likert scale (0 to 4); all other groups consisted of 23 items, with a 3-point Likert scale (0, 2, 4) for young pediatric, a 5-point Likert scale for pediatric and teens groups. All reported scores were transformed on a scale from 0 to 100 for each domain where 0=100, 1=75, 2=50, 3=25, and 4=0. Higher scores correspond with higher quality of life.
Time frame: Baseline, Month 12 and 24
Population: TP included all participants who received beti-cel. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome and number analyzed signifies those participants who were evaluable at specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LentiGlobin BB305 Drug Product | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Scores at Months 12 and 24 | Parent total score: Change at Month 12 | -6.20 Score on a scale | Standard Deviation 12.948 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Scores at Months 12 and 24 | Parent total score: Change at Month 24 | -3.49 Score on a scale | Standard Deviation 19.621 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Scores at Months 12 and 24 | Patient total score: Change at Month 12 | 2.96 Score on a scale | Standard Deviation 14.857 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Scores at Months 12 and 24 | Patient total score: Change at Month 24 | 4.84 Score on a scale | Standard Deviation 11.321 |
Secondary
Change From Baseline in Serum Ferritin
Serum ferritin was commonly used for an indirect estimation of body iron stores. Although sensitive, it is not specific for iron overload as it can be elevated in a variety of infectious and inflammatory states, and in the presence of cytolysis. Change from baseline in serum ferritin at Months 12 and 24 was reported.
Time frame: Baseline, Month 12 and 24
Population: TP included all participants who received beti-cel. Participants are evaluable for TI if they had completed the study (i.e., completed the Month 24 Visit), achieved TI, or did not achieve TI during the study. Here, number analyzed signifies those participants who were evaluable at specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LentiGlobin BB305 Drug Product | Change From Baseline in Serum Ferritin | Change at Month 24 | -605.2 picomole per liter (pmol/L) | Standard Deviation 1716.9 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Serum Ferritin | Change at Month 12 | 87.3 picomole per liter (pmol/L) | Standard Deviation 1302.76 |
Secondary
Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Months 12 and 24
SF-36 was designed to measure health-related quality of life in adults. The instrument consisted of 36 items that were aggregated into 8 multi-item scales (physical functioning \[1=yes, limited a lot, to 3=no, not limited at all\], role-physical \[1=all of time, to 5=none of time\], bodily pain \[1=very severe, to 6=none\], general health \[1=poor, to 5=excellent\], vitality \[1=none of time, to 5=all of time\], social functioning \[1=all of time, to 5=none of time\], role emotional \[1=all of time, to 5=none of time\] and mental health \[1=all of time, to 5=none of the time\]). The 8 scales were summarized as Physical Component Summary (PCS) score (physical functioning, role-physical, bodily pain, general health scales) and Mental Component Summary (MCS) score (vitality, social functioning, role-emotional, mental health scales). Reported summary scores were transformed on a scale from 0-100 (higher scores corresponded with higher quality of life), with change from baseline results being presented.
Time frame: Baseline, Months 12 and 24
Population: TP included all participants who received beti-cel. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LentiGlobin BB305 Drug Product | Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Months 12 and 24 | Physical Component Summary: Change at Month 12 | -0.89 Score on a scale | Standard Deviation 10.289 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Months 12 and 24 | Physical Component Summary: Change at Month 24 | 1.09 Score on a scale | Standard Deviation 8.167 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Months 12 and 24 | Mental Component Summary: Change at Month 12 | 2.42 Score on a scale | Standard Deviation 7.637 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Months 12 and 24 | Mental Component Summary: Change at Month 24 | 2.08 Score on a scale | Standard Deviation 7.281 |
Secondary
Duration of Transfusion Independence (TI)
Duration of TI was calculated as the time from the start of TI (i.e. first Hb \>=9 with no transfusions in the preceding 60 days) up to the last available Hb at which the TI criteria are still met using Kaplan-Meier methodology.
Time frame: From start of TI up to Month 24 (actual maximum time frame of up to approximately 25 months due to visit window)
Population: TP included all participants who received beti-cel. Participants evaluable for TI are defined as participants who have achieved TI, have not achieved TI in their parent study, or completed their parent study. Here, overall number of participants analyzed signifies those participants who achieved TI. Data are presented through the Month 24 Visit based on calendar dates and including visit windows.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Duration of Transfusion Independence (TI) | 20.86 Months |
Secondary
Number of Participants Who Used Therapeutic Phlebotomy Post Drug Product Infusion
Therapeutic phlebotomy could be used in lieu of chelation in participants who had Hb consistently \>= 11 g/dL and who were no longer receiving regular transfusions, at the discretion of the investigator. Number of participants who used therapeutic phlebotomy post Drug Product infusion for up to Month 24 were reported.
Time frame: From drug product infusion through Month 24
Population: TP included all participants who received beti-cel.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Number of Participants Who Used Therapeutic Phlebotomy Post Drug Product Infusion | 2 Participants |
Secondary
Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24
Number of participants with unsupported total Hb levels (\>=10 g/dL, \>=11 g/dL, \>=12 g/dL, \>=13 g/dL, and \>=14 g/dL) meeting the thresholds were reported at Months 6, 9, 12, 18 and 24. Participants were evaluable if they had an unsupported total Hb measurement at the specific timepoint, where unsupported total Hb level is defined as the total Hb measurement level without any acute or chronic pRBC transfusions within 60 days prior to the measurement date.
Time frame: At Months 6, 9, 12, 18 and 24
Population: TP included all participants who received beti-cel. Here, Overall number of participants analyzed signifies those participants who had a least 1 unsupported total Hb measurement during Study HGB-212 and number analyzed signifies those participants who had an unsupported total Hb measurement at the specific timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 6 (>=11 g/dL) | 4 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 12 (>=12 g/dL) | 3 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 12 (>=13 g/dL) | 2 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 6 (>=10 g/dL) | 11 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 6 (>=12 g/dL) | 3 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 6 (>=13 g/dL) | 1 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 6 (>=14 g/dL) | 0 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 9 (>=10 g/dL) | 13 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 9 (>=11 g/dL) | 5 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 9 (>=12 g/dL) | 3 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 9 (>=13 g/dL) | 1 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 9 (>=14 g/dL) | 0 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 12 (>=10 g/dL) | 12 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 12 (>=11 g/dL) | 6 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 12 (>=14 g/dL) | 1 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 18 (>=10 g/dL) | 13 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 18 (>=11 g/dL) | 5 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 18 (>=12 g/dL) | 3 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 18 (>=13 g/dL) | 3 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 18 (>=14 g/dL) | 0 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 24 (>=10 g/dL) | 10 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 24 (>=11 g/dL) | 7 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 24 (>=12 g/dL) | 3 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 24 (>=13 g/dL) | 3 Participants |
| LentiGlobin BB305 Drug Product | Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 | At Month 24 (>=14 g/dL) | 1 Participants |
Secondary
Percentage of Participants Who Had a Reduction of At Least 50%, 60%, 75%, 90% or 100% in the Annualized pRBCs Transfusion Volume
Percentage of participants with a reduction in the annualized mL/kg pRBCs transfused from 12 months post-drug product infusion through Month 24 (approximately a 12-month period) of at least 50%, 60%, 75%, 90% or 100% compared to the annualized mL/kg pRBC transfusion requirement during the 24 months prior to enrollment.
Time frame: 12 months post-drug product infusion through Month 24
Population: TP included all participants who received beti-cel.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LentiGlobin BB305 Drug Product | Percentage of Participants Who Had a Reduction of At Least 50%, 60%, 75%, 90% or 100% in the Annualized pRBCs Transfusion Volume | Reduction at >= 50% | 94.4 Percentage of participants |
| LentiGlobin BB305 Drug Product | Percentage of Participants Who Had a Reduction of At Least 50%, 60%, 75%, 90% or 100% in the Annualized pRBCs Transfusion Volume | Reduction at >= 60% | 94.4 Percentage of participants |
| LentiGlobin BB305 Drug Product | Percentage of Participants Who Had a Reduction of At Least 50%, 60%, 75%, 90% or 100% in the Annualized pRBCs Transfusion Volume | Reduction at >= 75% | 94.4 Percentage of participants |
| LentiGlobin BB305 Drug Product | Percentage of Participants Who Had a Reduction of At Least 50%, 60%, 75%, 90% or 100% in the Annualized pRBCs Transfusion Volume | Reduction at >= 90% | 94.4 Percentage of participants |
| LentiGlobin BB305 Drug Product | Percentage of Participants Who Had a Reduction of At Least 50%, 60%, 75%, 90% or 100% in the Annualized pRBCs Transfusion Volume | Reduction at 100% | 88.9 Percentage of participants |
Secondary
Percentage of Participants Who Have Achieved Transfusion Independence (TI) at Month 24
TI was defined as a weighted average hemoglobin (Hb) \>= 9 grams per deciliter (g/dL) without any packed red blood cell (pRBC) transfusions for a continuous period of \>= 12 months at any time during the study after drug product infusion.
Time frame: At Month 24 post-transplant
Population: TP included all participants who received beti-cel. Participants evaluable for TI are defined as participants who have achieved TI, have not achieved TI in their parent study, or completed their parent study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Percentage of Participants Who Have Achieved Transfusion Independence (TI) at Month 24 | 88.9 Percentage of participants |
Secondary
Percentage of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion
Percentage of participants who have not received chelation therapy for at least 6 months following drug product infusion were reported.
Time frame: From 6 to 24 months
Population: TP included all participant who received beti-cel.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Percentage of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion | 61.1 Percentage of participants |
Secondary
Percentage of Participants Who Meet the Definition of Transfusion Reduction (TR)
TR was defined as demonstration of a 60 percent (%) reduction in the annualized volume of pRBC transfusion requirements (in milliliter per kilogram \[mL/kg\]) in the post-treatment time period from 12 Months post-drug product infusion through Month 24 compared to the annualized mL/kg pRBC transfusion requirement during the 24 months prior to study enrollment.
Time frame: From 12 to 24 months post-transplant
Population: TP included all participants who received beti-cel. Participants evaluable for TI are defined as participants who have achieved TI, have not achieved TI in their parent study, or completed their parent study. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Percentage of Participants Who Meet the Definition of Transfusion Reduction (TR) | 94.4 Percentage of participants |
Secondary
Time From Drug Product Infusion to Achievement of Transfusion Independence (TI)
Time from drug product infusion to achievement of TI was calculated as the time from drug product infusion to the first hemoglobin at which a participant can be declared as TI (that is to 'start of TI + \>= 12 months', dependent on Hb lab schedule).
Time frame: From drug product infusion to start of TI (up to Month 24 [actual maximum time frame of up to approximately 25 months due to visit window])
Population: TP included all participants who received beti-cel. Participants evaluable for TI are defined as participants who have achieved TI, have not achieved TI in their parent study, or completed their parent study. Here, overall number of participants analyzed signifies those participants who achieved TI. Data are presented through the Month 24 Visit based on calendar dates and including visit windows.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Time From Drug Product Infusion to Achievement of Transfusion Independence (TI) | 15.67 Months |
Secondary
Time From Drug Product Infusion to Last pRBC Transfusion
Time from drug product infusion to last pRBC transfusion was reported.
Time frame: From start of drug product infusion up to Month 24
Population: TP included all participants who received beti-cel.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Time From Drug Product Infusion to Last pRBC Transfusion | 0.986 months |
Secondary
Time From Last Iron Chelation Use to Last Follow-up
Time from last iron chelation use to last follow-up to 24 months was reported.
Time frame: From last Iron Chelation up to Month 24 (actual maximum time frame of up to approximately 29 months due to visit window)
Population: TP included all participants who received beti-cel. Participants were evaluable for this endpoint if they had not received iron chelation therapy for at least 6 months following drug product infusion. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome. Data are presented through the Month 24 Visit based on calendar dates and including visit windows.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Time From Last Iron Chelation Use to Last Follow-up | 17.81 Months |
Secondary
Time From Last pRBC Transfusion to 24 Months
Time From Last pRBC Transfusion to the Month 24 was reported.
Time frame: From last pRBC Transfusion up to Month 24 (actual maximum time frame of up to approximately 27 months due to visit window)
Population: TP included all participants who received beti-cel. Data are presented through the Month 24 Visit based on calendar dates and including visit windows.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Time From Last pRBC Transfusion to 24 Months | 23.211 Months |
Secondary
Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24
Unsupported total Hb level was defined as the total Hb measurement level without any acute or chronic pRBC transfusions within 60 days prior to the measurement date.
Time frame: At Month 6, 9, 12, 18 and 24
Population: TP included all participant who received beti-cel. Here, overall number of participants analyzed signifies those participants who had a least 1 unsupported total Hb measurement during Study HGB-212 and number analyzed signifies those participants who had an unsupported total Hb measurement at the specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LentiGlobin BB305 Drug Product | Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24 | At Month 6 | 10.41 g/dL | Standard Deviation 1.253 |
| LentiGlobin BB305 Drug Product | Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24 | At Month 9 | 10.61 g/dL | Standard Deviation 1.338 |
| LentiGlobin BB305 Drug Product | Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24 | At Month 12 | 10.65 g/dL | Standard Deviation 1.619 |
| LentiGlobin BB305 Drug Product | Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24 | At Month 18 | 11.00 g/dL | Standard Deviation 1.483 |
| LentiGlobin BB305 Drug Product | Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24 | At Month 24 | 10.82 g/dL | Standard Deviation 1.58 |
Secondary
Weighted Average Hemoglobin (Hb) During Transfusion Independence (TI)
Weighted average Hb was defined as the weighted average of Hb values without any pRBC transfusions in the proceeding 60 days for a given subject. Ratio of the time between two Hb values and the time between the first and the last Hb values was used as the weight for calculation.
Time frame: Timeframe varied by subject. For a given subject, the endpoint was calculated from 60 days after the last pRBC transfusion (so transfused blood did not confound the weighted average calculation) through the Month 24 Visit for that subject.
Population: TP included all participants who received beti-cel. Participants evaluable for TI are defined as participants who have achieved TI, have not achieved TI in their parent study, or completed their parent study. Here, overall number of participants analyzed signifies those participants who achieved TI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LentiGlobin BB305 Drug Product | Weighted Average Hemoglobin (Hb) During Transfusion Independence (TI) | 10.817 gram per deciliter (g/dL) | Standard Deviation 1.2535 |
Secondary
Weighted Average Nadir Hemoglobin (Hb)
The weighted average nadir Hb was defined as the most recent Hb prior to each pRBC transfusion, on the day of transfusion or within 3 days and, if there was a period of more than 60 days without transfusion, all Hb records between Day 61 and last follow-up or next transfusion (inclusive) was included. The weighted average nadir Hb during the period of 12 months post-drug product infusion to Month 24 was compared to the weighted average nadir Hb during the 24 months prior to enrollment.
Time frame: 12 months post-drug product infusion through Month 24
Population: TP included all participant who received beti-cel.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LentiGlobin BB305 Drug Product | Weighted Average Nadir Hemoglobin (Hb) | 10.653 g/dL | Standard Deviation 1.5096 |