A Safety and Efficacy Study Evaluating CTX001 in Subjects With Severe Sickle Cell Disease

A VOC is a condition of SCD characterized by vaso-occlusion presenting as recurrent pain episodes. The percentage of participants who remain VOC free after achieving VF12 were data reported in the outcome measure.

Neutrophil engraftment is defined as the first day of 3 consecutive measurements of absolute neutrophil count (ANC)≥500/μL on 3 different days, within 42 days after exa-cel infusion without the use of unmodified CD34+ cells after reaching the nadir, defined as ANC <500/µL.

Neutrophil engraftment is defined as the first day of 3 consecutive measurements of absolute neutrophil count (ANC)≥500/μL on 3 different days, without use of the unmodified CD34+ cells after reaching the nadir, defined as ANC<500/μL. Time to neutrophil engraftment was calculated by the neutrophil engraftment date subtract exa-cel infusion date +1.

Platelet engraftment is defined as the first day of 3 consecutive measurements of unsupported (no platelet transfusions for the last 7 days) platelet ≥50,000/μL on 3 different days after Exa-cel infusion. For participants discharged early day 7 after the last platelet transfusion will be the day of platelet engraftment, as long as 3 subsequent and consecutive unsupported measurements on 3 different days are >50,000/μL. For participants who have been discharged prior to platelet engraftment, it is recommended to collect blood every 2 to 3 days to obtain an accurate assessment of platelet engraftment. Time to platelet engraftment was defined as first of 3 consecutive measurements on 3 different days with platelet ≥50 × 109/L without a platelet transfusion for 7 consecutive days.

The transplant-related mortality is defined as death related to Busulfan and/or exa-cel infusion. The number and proportion of TRM participants who have died within 100 days, or with at least 100 days post exa-cel infusion.

The transplant-related mortality is defined as death related to Busulfan and/or exa-cel infusion. The number and proportion of TRM within 12 months will be summarized for participants who have died within 12 months, or with at least 12 months post exa-cel infusion.

All-cause mortality from exa-cel infusion up to 2 years

The HF12 means Free from inpatient hospitalization for severe vaso-occlusive crises (VOCs) and sustained for at least 12 months after exa-cel infusion.

The VF12 defines absence of any severe vaso-occlusive crises (VOCs) for at least 12 consecutive months after exa-cel infusion. Only severe VOCs adjudicated by an outcome measure adjudication committee as meeting the protocol definition of severe VOCs were included in the analysis. Relative reduction from baseline was calculated as 100 % × (Baseline value - post-baseline value) / Baseline value. Annualized rate is calculated by the Total number of events/number of years.

Percentage of participants with at least 90% relative reduction from baseline was reported. The percentages were calculated relative to the number of participants who did not achieve VF12.

Percentage of participants with at least 80% relative reduction from baseline was reported. The percentages were calculated relative to the number of participants who did not achieve VF12.

Percentage of participants with at least 75% relative reduction from baseline was reported. The percentages were calculated relative to the number of participants who did not achieve VF12.

Percentage of participants with at least 50% relative reduction from baseline was reported. The percentages were calculated relative to the number of participants who did not achieve VF12.

The VF12 means the absence of any severe VOC for at least 12 consecutive months after exa-cel infusion. The evaluation of the severe VOC free duration in participants who achieved VF12 started 60 days after the last RBC transfusion for post transplant support or SCD management.

The HF12 means Free from inpatient hospitalization for severe vaso-occlusive crises (VOCs) and sustained for at least 12 months after exa-cel infusion. Relative reduction from baseline is calculated as 100% × (Baseline value - post-baseline value) / Baseline value. Annualized rate is calculated by the Total number of events/number of years.

Only severe VOCs adjudicated by an outcome measure adjudication committee as meeting the protocol definition of severe VOCs are included in the analysis.

The HF12 means Free from inpatient hospitalization for severe vaso-occlusive crises (VOCs) and sustained for at least 12 months after exa-cel infusion. Relative reduction from baseline is calculated as 100% × (Baseline value - post-baseline value) / Baseline value. Annualized rate is calculated by the Total number of events/number of years.

Only severe VOCs adjudicated by an outcome measure adjudication committee as meeting the protocol definition of severe VOCs are included in the analysis.

The HbF evaluation started 60 days after the last RBC transfusion for post transplant support or SCD management. The last RBC transfusion refers to that in the period of the initial RBC transfusions for post transplant support or SCD management.

The HbF evaluation started 60 days after the last RBC transfusion for post transplant support or SCD management. The last RBC transfusion refers to that in the period of the initial RBC transfusions for post transplant support or SCD management.

The HbF evaluation started 60 days after the last RBC transfusion for post transplant support or SCD management. The last RBC transfusion refers to that in the period of the initial RBC transfusions for post transplant support or SCD management.

The evaluation of the number of annualized RBC units transfused after exa-cel infusion started 12 months after exa-cel infusion.

Relative reduction from baseline = 100% × (Baseline value - post baseline value)/Baseline value. The evaluation of the number of annualized RBC units transfused after exa-cel infusion started 12 months after exa-cel infusion.

The 11-point pain numerical rating scale (NRS) is used to measures pain intensity on a 1-dimensional score ranging from 0 (no pain) to 10 (worst possible pain).

The 11 point pain numerical rating scale (NRS) is used to measures pain intensity on a 1 dimensional score ranging from 0 (no pain) to 10 (worst possible pain).

The EQ-5D VAS is a version of the EQ-5D designed for children and adolescents S). The EQ VAS records the subject's self-rated health on a 100-point VAS scale that ranged from 0 (worst imaginable health) to 100 (best imaginable health) points.

The EQ-5D VAS is a version of the EQ-5D designed for children and adolescents S). The EQ VAS records the subject's self-rated health on a 100-point VAS scale that ranged from 0 (worst imaginable health) to 100 (best imaginable health) points.

The Functional Assessment of Cancer Therapy-Bone Marrow Transplant scale (FACT-BMT) is a quality of life instrument that assesses the effects of bone marrow transplantation (BMT) on a patient's physical, social/family, emotional, and functional well-being while taking into consideration BMT-specific concerns. The assessment has different questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-148, with higher scores indicating higher levels of overall well-being.

ASCQ-Me is a disease-specific HRQoL questionnaire for adults with sickle cell disease that assesses Emotional Impact, Pain Impact, Social Functioning Impact, Stiffness Impact, Sleep Impact, Pain Episode Frequency, and Pain Episode Severity. Domain scores are reported as T-scores standardized to a reference population where mean = 50, and SD = 10. A change of approximately 5 points (1/2 SD) is considered clinically meaningful. An increase of 5 points indicates improvement for the impact domains, whereas a decrease of 5 points indicates improvement for the Pain Episode Frequency and Pain Episode Severity domains. For impact domain items higher score indicates better HRQoL and lower disease burden. For Pain items lower score indicates a better outcome. Scores are interpreted relative to the reference population mean of 50, taking into account the direction of scoring for each domain.

PedsQL scores were used to assess quality of life of participants. It is a standardized, generic instrument for measuring health related quality of life (HRQoL) in children and adolescents. It includes different domains (Psychosocial health, physical functioning, emotional functioning, social functioning, and school functioning). When completing the PedsQL questionnaires, respondents were asked to provide a response on a 5-point scale ranging from 0 (never a problem) to 4 (almost always a problem). Responses were then transformed to a 0 to 100 score, with higher scores reflecting better quality of life.

The PedsQL Sickle Cell Disease Module (PedsQL SCD) is a disease-specific module of the PedsQL. The tool measures self-reported health-related quality of life in participants with SCD across 9 domains: pain and hurt, pain impact, pain management (mgmt), worry I, worry II, emotions, treatment, communication I, and communication II. When completing the PedsQL SCD Module questionnaires, respondents were asked to provide a response on a 5-point scale ranging from 0 (never a problem) to 4 (almost always a problem). Responses were then transformed to a 0 to 100 score, with higher scores reflecting better quality of life.