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NCT Number: NCT03745287

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

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.

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Key information

Conditions

Sickle Cell Disease Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hematological Diseases Hemic and Lymphatic Diseases Hemoglobinopathies

Age range

12 year–35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Hopital Universitaire des Enfants Reine Fabiola (HUDERF), Brussels, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

CTX001

Biological

Administered by IV infusion following myeloablative conditioning with busulfan.

Other names: Exagamglogene autotemcel, Exa-cel

Primary outcomes

  1. 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

  2. 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

  3. Time to engraftment

    Time frame: From CTX001 infusion up to 2 years after CTX001 infusion

  4. Frequency and severity of collected adverse events (AEs)

    Time frame: From screening to 2 years after CTX001 infusion

  5. Incidence of transplant-related mortality (TRM) within 100 days after CTX001 infusion

    Time frame: Within 100 days after CTX001 infusion

  6. Incidence of TRM within 1 year after CTX001 infusion

    Time frame: Within 1 year after CTX001 infusion

  7. All-cause mortality

    Time frame: 2 years after mobilization

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Change in number of units of RBC transfused for SCD-related indications

    Time frame: 6 months up to 2 years after CTX001 infusion

  12. HbF concentration over time

    Time frame: 1 month up to 2 years after CTX001 infusion

  13. Hb concentration over time

    Time frame: From the time of CTX001 up to 2 years after CTX001 infusion

  14. Change from baseline in indirect bilirubin over time

    Time frame: From baseline (pre-infusion) up to 2 years after CTX001 infusion

  15. Change from baseline in reticulocyte count over time

    Time frame: From baseline (pre-infusion) up to 2 years after CTX001 infusion

  16. Change from baseline in haptoglobin over time

    Time frame: From baseline (pre-infusion) up to 2 years after CTX001 infusion

  17. Change from baseline in lactate dehydrogenase over time

    Time frame: From baseline (pre-infusion) up to 2 years after CTX001 infusion

  18. 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

  19. 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

  20. 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.

  21. 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"

  22. Change in PRO over time assessed using EQ-5D-Youth (EQ-5D-Y)

    Time frame: 3 months up to 2 years after CTX001 infusion

  23. 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.

  24. 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.

  25. Change in PRO over time assessed using pediatric quality of life inventory (PedsQL)

    Time frame: 3 months up to 2 years after CTX001 infusion

  26. Change in PRO over time assessed using PedsQL sickle cell disease module

    Time frame: 3 months up to 2 years after CTX001 infusion

Sponsors and collaborators

Lead sponsor

Vertex Pharmaceuticals Incorporated

Industry

Collaborators

  • CRISPR Therapeutics

Registry information

Official study title

A Phase 1/2/3 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

Important dates

Study start
2018
Primary completion
2025
Study completion
2025
First posted
Nov 19, 2018
Registry last updated
Aug 11, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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