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

Primary Outcome Measures

1. Proportion of subjects who have not experienced any severe vaso-occlusive crisis (VOC) for at least 12 consecutive months (VF12)
2. Proportion of subjects with engraftment (first day of three consecutive measurements of absolute neutrophil count [ANC] ≥500/µL on three different days)
3. Time to engraftment
4. Frequency and severity of collected adverse events (AEs)
5. Incidence of transplant-related mortality (TRM) within 100 days after CTX001 infusion
6. Incidence of TRM within 1 year after CTX001 infusion
7. All-cause mortality

Secondary Outcome Measures

1. Proportion of subjects free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12)
2. Proportion of subjects who have not experienced any severe VOC for at least 9 consecutive months (VF9) any time after CTX001 infusion
3. Proportion of subjects with 90 percent (%), 80%, 75% or 50% reduction in annualized rate of severe VOCs
4. Relative change from baseline in annualized rate of severe VOCs
5. Duration of severe VOC free in subjects who have achieved VF12
6. Relative Change from baseline in rate of inpatient hospitalization for severe VOCs
7. Relative change from baseline in annualized duration of hospitalization for severe VOCs
8. Proportion of subjects with sustained HbF ≥20% for at least 3 months
9. Proportion of subjects with sustained HbF ≥20% for at least 12 months
10. Proportion of subjects with sustained HbF ≥20% for at least 6 months
11. Change in number of units of RBC transfused for SCD-related indications
12. HbF concentration over time
13. Hb concentration over time
14. Change from baseline in indirect bilirubin over time
15. Change from baseline in reticulocyte count over time
16. Change from baseline in haptoglobin over time
17. Change from baseline in lactate dehydrogenase over time
18. Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time
19. Proportion of alleles with intended genetic modification present in CD34+ cells of bone marrow over time
20. 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.
21. 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"
22. Change in PRO over time assessed using EQ-5D-Youth (EQ-5D-Y)
23. 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.
24. 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.
25. Change in PRO over time assessed using pediatric quality of life inventory (PedsQL)
26. Change in PRO over time assessed using PedsQL sickle cell disease module