This is a single-arm, open-label, multi-site, single-dose Phase 1/2/3 study in subjects with severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) using CTX001.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
63
Administered by IV infusion following myeloablative conditioning with busulfan.
Lucile Packard Children's Hospital of Stanford University
Palo Alto, California, United States
Proportion of subjects who have not experienced any severe vaso-occlusive crisis (VOC) for at least 12 consecutive months (VF12)
Time frame: From 60 days after last RBC transfusion up to 2 years after CTX001 infusion
Proportion of subjects with engraftment (first day of three consecutive measurements of absolute neutrophil count [ANC] ≥500/µL on three different days)
Time frame: Within 42 days after CTX001 infusion
Time to engraftment
Time frame: From CTX001 infusion up to 2 years after CTX001 infusion
Frequency and severity of collected adverse events (AEs)
Time frame: From screening to 2 years after CTX001 infusion
Incidence of transplant-related mortality (TRM) within 100 days after CTX001 infusion
Time frame: Within 100 days after CTX001 infusion
Incidence of TRM within 1 year after CTX001 infusion
Time frame: Within 1 year after CTX001 infusion
All-cause mortality
Time frame: 2 years after mobilization
Proportion of subjects free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12)
Time frame: From 60 days after last RBC transfusion up to 2 years after CTX001 infusion
Proportion of subjects who have not experienced any severe VOC for at least 9 consecutive months (VF9) any time after CTX001 infusion
Time frame: From 60 days after last RBC transfusion up to 2 years after CTX001 infusion
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Ann & Robert Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
University of Illinois at Chicago Hospitals and Health Systems
Chicago, Illinois, United States
Columbia University Medical Center (21+ years)
New York, New York, United States
Columbia University Medical Center (≤21 years)
New York, New York, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers
Nashville, Tennessee, United States
Methodist Children's Hospital/Texas Transplant Institute
San Antonio, Texas, United States
Hopital Universitaire des Enfants Reine Fabiola (HUDERF)
Brussels, Belgium
...and 7 more locations
Proportion of subjects with 90 percent (%), 80%, 75% or 50% reduction in annualized rate of severe VOCs
Time frame: From 60 days after last RBC transfusion up to 2 years after CTX001 infusion
Relative change from baseline in annualized rate of severe VOCs
Time frame: From 60 days after last RBC transfusion up to 2 years after CTX001 infusion
Duration of severe VOC free in subjects who have achieved VF12
Time frame: From 60 days after last RBC transfusion up to 2 years after CTX001 infusion
Relative Change from baseline in rate of inpatient hospitalization for severe VOCs
Time frame: From 60 days after last RBC transfusion up to 2 years after CTX001 infusion
Relative change from baseline in annualized duration of hospitalization for severe VOCs
Time frame: From 60 days after last RBC transfusion up to 2 years after CTX001 infusion
Proportion of subjects with sustained HbF ≥20% for at least 3 months
Time frame: From 60 days after last RBC transfusion up to 2 years after CTX001 infusion
Proportion of subjects with sustained HbF ≥20% for at least 12 months
Time frame: From 60 days after last RBC transfusion up to 2 years after CTX001 infusion
Proportion of subjects with sustained HbF ≥20% for at least 6 months
Time frame: From 60 days after last RBC transfusion up to 2 years after CTX001 infusion
Change in number of units of RBC transfused for SCD-related indications
Time frame: 6 months up to 2 years after CTX001 infusion
HbF concentration over time
Time frame: 1 month up to 2 years after CTX001 infusion
Hb concentration over time
Time frame: From the time of CTX001 up to 2 years after CTX001 infusion
Change from baseline in indirect bilirubin over time
Time frame: From baseline (pre-infusion) up to 2 years after CTX001 infusion
Change from baseline in reticulocyte count over time
Time frame: From baseline (pre-infusion) up to 2 years after CTX001 infusion
Change from baseline in haptoglobin over time
Time frame: From baseline (pre-infusion) up to 2 years after CTX001 infusion
Change from baseline in lactate dehydrogenase over time
Time frame: From baseline (pre-infusion) up to 2 years after CTX001 infusion
Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time
Time frame: 1 month up to 2 years after CTX001 infusion
Proportion of alleles with intended genetic modification present in CD34+ cells of bone marrow over time
Time frame: 6 months up to 2 years after CTX001 infusion
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.
Time frame: 3 months up to 2 years after CTX001 infusion
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"
Time frame: 3 months up to 2 years after CTX001 infusion
Change in PRO over time assessed using EQ-5D-Youth (EQ-5D-Y)
Time frame: 3 months up to 2 years after CTX001 infusion
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.
Time frame: 3 months up to 2 years after CTX001 infusion
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.
Time frame: 3 months up to 2 years after CTX001 infusion
Change in PRO over time assessed using pediatric quality of life inventory (PedsQL)
Time frame: 3 months up to 2 years after CTX001 infusion
Change in PRO over time assessed using PedsQL sickle cell disease module
Time frame: 3 months up to 2 years after CTX001 infusion