Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Proportion of subjects who have not experienced any severe vaso-occlusive crisis (VOC) for at least 12 consecutive months (VF12) |
|
From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
|
| Primary |
Proportion of subjects with engraftment (first day of three consecutive measurements of absolute neutrophil count [ANC] =500/µL on three different days) |
|
Within 42 days after CTX001 infusion |
|
| Primary |
Time to engraftment |
|
From CTX001 infusion up to 2 years after CTX001 infusion |
|
| Primary |
Frequency and severity of collected adverse events (AEs) |
|
From screening to 2 years after CTX001 infusion |
|
| Primary |
Incidence of transplant-related mortality (TRM) within 100 days after CTX001 infusion |
|
Within 100 days after CTX001 infusion |
|
| Primary |
Incidence of TRM within 1 year after CTX001 infusion |
|
Within 1 year after CTX001 infusion |
|
| Primary |
All-cause mortality |
|
2 years after mobilization |
|
| Secondary |
Proportion of subjects free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12) |
|
From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
|
| Secondary |
Proportion of subjects who have not experienced any severe VOC for at least 9 consecutive months (VF9) any time after CTX001 infusion |
|
From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
|
| Secondary |
Proportion of subjects with 90 percent (%), 80%, 75% or 50% reduction in annualized rate of severe VOCs |
|
From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
|
| Secondary |
Relative change from baseline in annualized rate of severe VOCs |
|
From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
|
| Secondary |
Duration of severe VOC free in subjects who have achieved VF12 |
|
From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
|
| Secondary |
Relative Change from baseline in rate of inpatient hospitalization for severe VOCs |
|
From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
|
| Secondary |
Relative change from baseline in annualized duration of hospitalization for severe VOCs |
|
From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
|
| Secondary |
Proportion of subjects with sustained HbF =20% for at least 3 months |
|
From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
|
| Secondary |
Proportion of subjects with sustained HbF =20% for at least 12 months |
|
From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
|
| Secondary |
Proportion of subjects with sustained HbF =20% for at least 6 months |
|
From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
|
| Secondary |
Change in number of units of RBC transfused for SCD-related indications |
|
6 months up to 2 years after CTX001 infusion |
|
| Secondary |
HbF concentration over time |
|
1 month up to 2 years after CTX001 infusion |
|
| Secondary |
Hb concentration over time |
|
From the time of CTX001 up to 2 years after CTX001 infusion |
|
| Secondary |
Change from baseline in indirect bilirubin over time |
|
From baseline (pre-infusion) up to 2 years after CTX001 infusion |
|
| Secondary |
Change from baseline in reticulocyte count over time |
|
From baseline (pre-infusion) up to 2 years after CTX001 infusion |
|
| Secondary |
Change from baseline in haptoglobin over time |
|
From baseline (pre-infusion) up to 2 years after CTX001 infusion |
|
| Secondary |
Change from baseline in lactate dehydrogenase over time |
|
From baseline (pre-infusion) up to 2 years after CTX001 infusion |
|
| Secondary |
Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time |
|
1 month up to 2 years after CTX001 infusion |
|
| Secondary |
Proportion of alleles with intended genetic modification present in CD34+ cells of bone marrow over time |
|
6 months up to 2 years after CTX001 infusion |
|
| Secondary |
Change in patient-reported outcome (PRO) over time assessed using weekly pain-scale (11-point numerical rating scale [NRS]) |
The NRS is a 1-dimensional measure of reporting intensity of pain. The score of NRS ranges from 0 to 10 points, with higher values indicating a higher level of pain. |
3 months up to 2 years after CTX001 infusion |
|
| Secondary |
Change in PRO over time assessed using EuroQol quality of life scale (EQ-5D-5L) |
The EQ-5D-5L Questionnaire consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The EQ-5D comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and 5 levels: no problems to extreme problems. The subject marks the most appropriate statement in each dimension, resulting in a 1-digit number for that dimension. The digits can be combined in a 5-digit number describing the subject's health state. The EQ VAS records the subject's self-rated health on a 100-point VAS, endpoints labelled "the best health you can imagine" and "the worst health you can imagine" |
3 months up to 2 years after CTX001 infusion |
|
| Secondary |
Change in PRO over time assessed using EQ-5D-Youth (EQ-5D-Y) |
|
3 months up to 2 years after CTX001 infusion |
|
| Secondary |
Change in PRO over time assessed using functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) questionnaire |
The FACT-BMT Questionnaire includes physical, social, family, emotional, and functional well-being, and treatment specific concerns of bone marrow transplantation. Each statement has a 5-point Likert-type response scale ranging from 0=not at all to 4=very much. The subject marks one number per line as it applies to the past 7 days. Questionnaires are then scored; the higher the score, the better the quality of life. |
3 months up to 2 years after CTX001 infusion |
|
| Secondary |
Change in PRO over time assessed using adult sickle cell quality of life measurement system (ASCQ-Me) |
ASCQ-Me comprises measures to assess physical, mental and social health along with information on severity of disease. It includes the following domains: emotional impact, pain impact, pain episodes, sleep impact, social functioning impact, stiffness impact and SCD medical history checklist. ASCQ-Me domains are scored using T-score metric with mean of 50 for reference population and SD of 10. Higher scores indicate healthier status. |
3 months up to 2 years after CTX001 infusion |
|
| Secondary |
Change in PRO over time assessed using pediatric quality of life inventory (PedsQL) |
|
3 months up to 2 years after CTX001 infusion |
|
| Secondary |
Change in PRO over time assessed using PedsQL sickle cell disease module |
|
3 months up to 2 years after CTX001 infusion |
|
