Beta-Thalassemia
Conditions
Brief summary
This is a single-arm, multi-site, single-dose, Phase 3 study in 23 participants less than or equal to (\<=) 50 years of age with transfusion-dependent β-thalassemia (TDT), also known as β-thalassemia major, who do not have a β0 mutation at both alleles of the hemoglobin β (HBB) gene. 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 \<= 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 β0 mutation at both alleles of the β-globin gene HBB. * 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. * Immediate family member with a known Familial Cancer Syndrome. * 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 Meet the Definition of Transfusion Independence (TI) | From 14 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 |
|---|---|---|
| Duration of Transfusion Independence (TI) | From start of TI up to Month 24 | Duration of TI was calculated as the time from the start of TI (that is (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. Duration of TI from start of TI up to Month 24 months was reported. |
| Time From Drug Product Infusion to Achievement of Transfusion Independence (TI) | From 14 months post-drug product infusion through Month 24 | 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) | From 60 days after the last pRBC transfusion through Month 24 | Weighted average Hb was defined as the weighted average of Hb values without any pRBC transfusions in the proceeding 60 days. The 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 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 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 were reported. |
| Annualized Volume of pRBC Transfusions | From 12 months post-drug product infusion through Month 24 | Annualized volume of pRBC transfusions from 12 months post-drug product infusion through Month 24 was reported. |
| 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 Month 24 | 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 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 Month 6, 9, 12, 18 and 24 | The 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 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 Meet the Definition of 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. Percentage of participants who met the definition of TI at Month 24 were evaluated |
| Time From Last Iron Chelation Use to Last Follow-up | Time from last iron chelation up to Month 24 (actual maximum time frame of up to approximately 27 months due to visit window) | Time from last iron chelation use to last follow-up to 24 months was reported. Participants were evaluable for this outcome if they had not received iron chelation therapy for at least 6 months following drug product infusion. |
| Percentage of Participants Who Used Therapeutic Phlebotomy Post Drug Product (DP) Infusion | Up to 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. Percentage of participants who used therapeutic phlebotomy post DP infusion for up to Month 24 were reported. |
| Annualized Phlebotomy Therapy Usage Following Drug Product Infusion | Up to 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 Concentration by Magnetic Resonance Imaging (MRI) | Baseline, Months 12 and 24 | Change From Baseline in liver Iron Content by Magnetic Resonance Imaging (MRI) at Months 12 and 24 were reported. |
| Change From Baseline in Cardiac T2* on MRI | Baseline, Months 12 and 24 | Change From Baseline in Cardiac T2\* on MRI at baseline, Month 12 and 24 was reported. |
| Change From Baseline in Serum Ferritin at Months 12 and 24 | Baseline, Months 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, Months 12 and 24 | PedsQL GCS designed to measure health-related quality of life in pediatric and adolescents (2 to 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 equated to better outcomes. |
| 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 which is a visual analog scale (VAS) which consists 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 feel most accurately reflects their current health state. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score | Baseline, Months 12 and 24 | FACT-BMT is assessed bone marrow transplant related quality of life in adults. It. 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, 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 \[1=all of time to 5=none of the time\]). Four domains comprised physical component summary (PCS) score (physical functioning, role-physical, bodily pain, general health) and remaining 4 domains comprised mental component summary (MCS) score (vitality, social functioning, role-emotional, mental health). Reported summary scores were transformed on a scale from 0 to 100. Higher scores corresponded with higher quality of life. |
| Percentage of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion | Up to Month 24 | Percentage of participants who have not received chelation therapy for at least 6 months following drug product infusion were reported. |
Countries
France, Germany, Italy, Thailand, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 9 centers from 08 August 2016 to 31 March 2022.
Pre-assignment details
A total of 24 participants initiated mobilization procedure, of which 23 participants aged less than or equal to (\<=) 50 years were treated with LentiGlobin BB305 Drug Product. As appropriate, data were analyzed at times based on Intent-to-Treat (ITT) population which included all 24 participants who initiated mobilization procedure.
Participants by arm
| Arm | Count |
|---|---|
| LentiGlobin BB305 Drug Product Participants aged \<= 50 years received a single IV infusion of LentiGlobin BB305 Drug Product at a dose of \>= 5.0\*10\^6 CD34+ cells/kg following myeloablative conditioning with busulfan (termed the Transplant population). | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Discontinued after mobilization due to pregnancy | 1 |
Baseline characteristics
| Characteristic | LentiGlobin BB305 Drug Product |
|---|---|
| Age, Continuous | 15.0 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 14 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 | 2 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 24 / 24 |
| serious Total, serious adverse events | 14 / 24 |
Outcome results
Primary
Percentage of Participants Who Meet the Definition of 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 14 to 24 months post-transplant
Population: Transplant Population (TP) included all participants who received beti-cel. All participants in the TP (23 participants) were evaluable for TI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Percentage of Participants Who Meet the Definition of Transfusion Independence (TI) | 91.3 Percentage of participants |
Secondary
Annualized Number of pRBC Transfusions
Annualized number of pRBC transfusions from 12 months post-drug product infusion through Month 24 were 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 | 0.95 pRBC transfusions per year | Standard Deviation 3.195 |
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: Up to 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 | 6.29 number of procedures per year | Standard Deviation 4.786 |
Secondary
Annualized Volume of pRBC Transfusions
Annualized volume 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 Volume of pRBC Transfusions | 11.607 milliliter/kilogram/year (mL/kg/year) | Standard Deviation 40.2964 |
Secondary
Change From Baseline in Cardiac T2* on MRI
Change From Baseline in Cardiac T2\* on MRI at 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 this outcome if they had available cardiac T2\* measurements at baseline and at the applicable follow-up timepoints. Here, Overall number of participants analyzed signifies those participants who had Cardiac T2\* data available at Baseline, Months 12 and 24 and number analyzed signifies those participants at specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LentiGlobin BB305 Drug Product | Change From Baseline in Cardiac T2* on MRI | At Month 12 | -1.0 milliseconds | Standard Deviation 5.93 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Cardiac T2* on MRI | At Month 24 | -1.6 milliseconds | Standard Deviation 7.42 |
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 which is a visual analog scale (VAS) which consists 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 feel most accurately reflects their current health state.
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 endpoint and number analyzed signifies those participants who were \>= 18 years at specific timepoint.
| 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 | 6.9 Score on a scale | Standard Deviation 11.93 |
| 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 | 9.7 Score on a scale | Standard Deviation 14.91 |
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 equated to better outcomes.
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 measure and number analyzed signifies those participants who were 11 to \<18 years at specific timepoint.
| 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 | 15.8 Score on a scale | Standard Deviation 20.6 |
| 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 | 20.9 Score on a scale | Standard Deviation 18.86 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score
FACT-BMT is assessed bone marrow transplant related quality of life in adults. It. 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 \>= 18 years for this outcome measure.
| 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 Score | Total Score: Change at Month 12 | 3.78 Score on a scale | Standard Deviation 16.994 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score | Total Score: Change at Month 24 | 2.15 Score on a scale | Standard Deviation 13.695 |
Secondary
Change From Baseline in Liver Iron Concentration by Magnetic Resonance Imaging (MRI)
Change From Baseline in liver Iron Content by Magnetic Resonance Imaging (MRI) at Months 12 and 24 were reported.
Time frame: Baseline, Months 12 and 24
Population: TP included all participants who received beti-cel. Participants were evaluable for this outcome if they had available liver iron content measurements at baseline and at the applicable follow-up timepoints. Here, number of participants 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 Concentration by Magnetic Resonance Imaging (MRI) | At Month 12 | 2.490 milligrams per gram (mg/g) | Standard Deviation 4.1546 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Liver Iron Concentration by Magnetic Resonance Imaging (MRI) | At Month 24 | 0.494 milligrams per gram (mg/g) | Standard Deviation 3.9957 |
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 to 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, 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 measure and number analyzed signifies those participants who were \<18 years 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 | Patient total score: Change at Month 12 | 6.82 Score on a scale | Standard Deviation 16.079 |
| 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 | 8.76 Score on a scale | Standard Deviation 12.071 |
| 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 | 6.03 Score on a scale | Standard Deviation 9.753 |
| 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 | 9.96 Score on a scale | Standard Deviation 16.997 |
Secondary
Change From Baseline in Serum Ferritin at Months 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.
Time frame: Baseline, Months 12 and 24
Population: TP included all participants who received beti-cel. Participants were evaluable for this endpoint if they had available serum ferritin measurements at baseline and at the applicable follow-up timepoints. 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 at Months 12 and 24 | At Month 12 | 167.3 picomole per Liter (pmol/L) | Standard Deviation 1887.67 |
| LentiGlobin BB305 Drug Product | Change From Baseline in Serum Ferritin at Months 12 and 24 | At Month 24 | -1163.8 picomole per Liter (pmol/L) | Standard Deviation 2435.58 |
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, 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 \[1=all of time to 5=none of the time\]). Four domains comprised physical component summary (PCS) score (physical functioning, role-physical, bodily pain, general health) and remaining 4 domains comprised mental component summary (MCS) score (vitality, social functioning, role-emotional, mental health). Reported summary scores were transformed on a scale from 0 to 100. 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 \>= 18 years for this outcome measure.
| 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: Change at Month 12 | 0.80 Score on a scale | Standard Deviation 4.838 |
| 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: Change at Month 24 | 0.82 Score on a scale | Standard Deviation 3.672 |
| 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: Change at Month 12 | 1.88 Score on a scale | Standard Deviation 8.201 |
| 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: Change at Month 24 | 0.93 Score on a scale | Standard Deviation 10.805 |
Secondary
Duration of Transfusion Independence (TI)
Duration of TI was calculated as the time from the start of TI (that is (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. Duration of TI from start of TI up to Month 24 months was reported.
Time frame: From start of TI up to Month 24
Population: TP included all participants who received beti-cel. All participants in the TP (23 participants) were evaluable for TI. Here, Overall number of participants analyzed signifies those participants who achieved TI (i.e. 21 participants as 2 participants did not achieve TI).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Duration of Transfusion Independence (TI) | 20.50 months |
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
The 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 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 Month 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-207 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 24 (>=10 g/dL) | 18 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) | 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 6 (>=10 g/dL) | 17 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) | 15 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) | 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 12 (>=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 12 (>=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 18 (>=10 g/dL) | 18 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) | 15 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) | 8 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) | 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 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 (>=11 g/dL) | 14 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) | 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 (>=13 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 6 (>=12 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 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) | 20 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) | 14 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) | 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 (>=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) | 18 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) | 14 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 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% | 95.7 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% | 91.3 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% | 91.3 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% | 91.3 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% | 91.3 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: Up to Month 24
Population: TP included all participants 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 | 43.5 percentage of participants |
Secondary
Percentage of Participants Who Meet the Definition of 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. Percentage of participants who met the definition of TI at Month 24 were evaluated
Time frame: At Month 24 post-transplant
Population: TP included all participants who received beti-cel. All participants in the TP (23 participants) were evaluable for TI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Percentage of Participants Who Meet the Definition of Transfusion Independence (TI) at Month 24 | 91.3 Percentage of participants |
Secondary
Percentage of Participants Who Used Therapeutic Phlebotomy Post Drug Product (DP) 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. Percentage of participants who used therapeutic phlebotomy post DP infusion for up to Month 24 were reported.
Time frame: Up to Month 24
Population: TP included all participants who received beti-cel.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Percentage of Participants Who Used Therapeutic Phlebotomy Post Drug Product (DP) Infusion | 30.4 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 14 months post-drug product infusion through Month 24
Population: TP included all participants who received beti-cel. All participants in the TP (23 participants) were evaluable for TI. Here, Overall number of participants analyzed signifies those participants who achieved TI (i.e. 21 participants as 2 participants did not achieve TI).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Time From Drug Product Infusion to Achievement of Transfusion Independence (TI) | 15.51 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 | 0.953 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. Participants were evaluable for this outcome if they had not received iron chelation therapy for at least 6 months following drug product infusion.
Time frame: Time from last iron chelation up to Month 24 (actual maximum time frame of up to approximately 27 months due to visit window)
Population: TP population. Here, Overall number of participants analyzed signifies those participants who have not received chelation therapy for at least 6 months following drug product infusion. Data are presented through the Month 24 Visit based on calendar dates and including visit windows. Notably due to institutional COVID-19 restrictions and scheduling conflicts one participant had a Month 24 visit 42 days out of this window.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Time From Last Iron Chelation Use to Last Follow-up | 23.56 months |
Secondary
Time From Last pRBC Transfusion to Month 24
Time From Last pRBC Transfusion to 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. Notably due to institutional COVID-19 restrictions and scheduling conflicts one participant had a Month 24 visit 42 days out of this window.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LentiGlobin BB305 Drug Product | Time From Last pRBC Transfusion to Month 24 | 23.228 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 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-207 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 | 11.24 g/dL | Standard Deviation 1.249 |
| LentiGlobin BB305 Drug Product | Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24 | At Month 9 | 11.22 g/dL | Standard Deviation 1.138 |
| LentiGlobin BB305 Drug Product | Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24 | At Month 12 | 11.45 g/dL | Standard Deviation 1.314 |
| LentiGlobin BB305 Drug Product | Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24 | At Month 18 | 11.80 g/dL | Standard Deviation 1.167 |
| LentiGlobin BB305 Drug Product | Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24 | At Month 24 | 11.77 g/dL | Standard Deviation 1.224 |
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. The 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: From 60 days after the last pRBC transfusion through Month 24
Population: TP included all participants who received beti-cel. All participants in the TP (23 participants) were evaluable for TI. Here, Overall number of participants analyzed signifies those participants who achieved TI (i.e. 21 participants as 2 participants did not achieve TI).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LentiGlobin BB305 Drug Product | Weighted Average Hemoglobin (Hb) During Transfusion Independence (TI) | 11.473 grams per deciliter (g/dL) | Standard Deviation 1.0395 |
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 participants who received beti-cel.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LentiGlobin BB305 Drug Product | Weighted Average Nadir Hemoglobin (Hb) | 9.546 g/dL | Standard Deviation 0.7007 |