A Safety and Efficacy Study Evaluating CTX001 in Subjects With Severe Sickle Cell Disease
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ClinicalTrials.gov Identifier: NCT03745287 |
Recruitment Status :
Recruiting
First Posted : November 19, 2018
Last Update Posted : January 22, 2021
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Condition or disease | Intervention/treatment | Phase |
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Sickle Cell Disease Hematological Diseases Hemoglobinopathies | Biological: CTX001 | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 45 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1/2 Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Severe Sickle Cell Disease |
Actual Study Start Date : | November 27, 2018 |
Estimated Primary Completion Date : | February 2021 |
Estimated Study Completion Date : | May 2022 |

Arm | Intervention/treatment |
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Experimental: CTX001
CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Subjects will receive a single infusion of CTX001 through a central venous catheter.
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Biological: CTX001
Administered by IV infusion following myeloablative conditioning with busulfan. |
- Proportion of subjects with HbF ≥20%, sustained for at least 3 months at the time of analysis, starting 6 months after CTX001 infusion [ Time Frame: 6 months up to 2 years after CTX001 infusion ]
- Proportion of subjects with engraftment (absolute neutrophil count [ANC] ≥500/µL for three consecutive 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 ]
- Relative change from baseline in annualized rate of severe vaso-occlusive crises (VOC) 6 months after CTX001 infusion [ Time Frame: 6 months up to 2 years after CTX001 infusion ]
- Change from baseline in annualized rate of severe VOC by at least 50% [ Time Frame: 6 months up to 2 years after CTX001 infusion ]
- Change from baseline in annualized rate of severe VOC by at least 65% [ Time Frame: 6 months up to 2 years after CTX001 infusion ]
- Number of subjects with absence of severe VOC events for at least 12 months [ Time Frame: 6 months up to 2 years after CTX001 infusion ]
- Relative Change from baseline in annualized rate of hospitalization for severe VOC 6 months after CTX001 infusion [ Time Frame: 6 months up to 2 years after CTX001 infusion ]
- Change from baseline in annualized duration of hospitalization for severe VOC 6 months after CTX001 infusion [ Time Frame: 6 months up to 2 years after CTX001 infusion ]
- Proportion of subjects with sustained HbF ≥20% for at least 3 months [ Time Frame: 3 months up to 2 years after CTX001 infusion ]
- Proportion of subjects with sustained HbF ≥20% for at least 3 months [ Time Frame: From the time of CTX001 infusion up to 2 years after CTX001 infusion ]
- Proportion of subjects with sustained HbF ≥20% for 6 months starting 6 months after CTX001 infusion [ Time Frame: 6 months 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 ]
- 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 bone marrow cells 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]) [ Time Frame: 3 months up to 2 years after CTX001 infusion ]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.
- Change in PRO over time assessed using EuroQol quality of life scale (EQ-5D-5L) [ Time Frame: 3 months up to 2 years after CTX001 infusion ]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"
- 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 [ Time Frame: 3 months up to 2 years after CTX001 infusion ]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.
- Change in PRO over time assessed using adult sickle cell quality of life measurement system (ASCQ-Me) [ Time Frame: 3 months up to 2 years after CTX001 infusion ]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.
- 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 ]

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Ages Eligible for Study: | 12 Years to 35 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Diagnosis of severe sickle cell disease as defined by:
- Documented severe sickle cell disease genotype
- History of at least two severe vaso-occlusive crisis events per year for the previous two years prior to enrollment
- Eligible for autologous stem cell transplant as per investigators judgment
Key Exclusion Criteria:
- An available 10/10 human leukocyte antigen (HLA)-matched related donor
- Prior hematopoietic stem cell transplant (HSCT)
- Clinically significant and active bacterial, viral, fungal, or parasitic infection
Other protocol defined inclusion/exclusion criteria may apply

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03745287
Contact: Medical Information | 6173416777 | medicalinfo@vrtx.com |
United States, California | |
Lucille Packard Children's Hospital of Stanford University | Recruiting |
Palo Alto, California, United States, 94304 | |
United States, Illinois | |
University of Illinois at Chicago Hospitals and Health Systems | Recruiting |
Chicago, Illinois, United States, 60612 | |
United States, New York | |
Columbia University Medical Center (21+ years) | Recruiting |
New York, New York, United States, 10032 | |
Columbia University Medical Center (≤21 years) | Recruiting |
New York, New York, United States, 10032 | |
United States, Pennsylvania | |
Children's Hospital of Philadelphia | Recruiting |
Philadelphia, Pennsylvania, United States, 19104 | |
United States, Tennessee | |
St. Jude Children's Research Hospital | Recruiting |
Memphis, Tennessee, United States, 38105 | |
The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers | Recruiting |
Nashville, Tennessee, United States, 37203 | |
United States, Texas | |
Methodist Children's Hospital/Texas Transplant Institute | Recruiting |
San Antonio, Texas, United States, 78229 | |
Belgium | |
Hopital Universitaire des Enfants Reine Fabiola (HUDERF) | Recruiting |
Brussels, Belgium | |
Canada | |
The Hospital for Sick Children | Recruiting |
Toronto, Canada | |
Germany | |
Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine, Paediatric Haemotology, Oncology and Stem Cell Transplantation | Recruiting |
Regensburg, Germany | |
Italy | |
Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCS | Recruiting |
Rome, Italy | |
United Kingdom | |
Imperial College Healthcare NHS Trust, Hammersmith Hospital | Recruiting |
London, United Kingdom |
Responsible Party: | Vertex Pharmaceuticals Incorporated |
ClinicalTrials.gov Identifier: | NCT03745287 |
Other Study ID Numbers: |
CTX001-121 |
First Posted: | November 19, 2018 Key Record Dates |
Last Update Posted: | January 22, 2021 |
Last Verified: | January 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Anemia, Sickle Cell Hemoglobinopathies Hematologic Diseases Anemia, Hemolytic, Congenital |
Anemia, Hemolytic Anemia Genetic Diseases, Inborn |