A Long-term Follow-up Study of Subjects With β-thalassemia or Sickle Cell Disease Treated With Autologous CRISPR-Cas9 Modified Hematopoietic Stem Cells (CTX001)

ClinicalTrials.gov processed this data on November 19, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

ENROLLING BY INVITATION (See Contacts and Locations)
Verified September 2024 by Vertex Pharmaceuticals Incorporated, CRISPR Therapeutics

Sponsor

Vertex Pharmaceuticals Incorporated

Information Provided by (Responsible Party)

Vertex Pharmaceuticals Incorporated

Clinicaltrials.gov Identifier

NCT04208529
Other Study ID Numbers: CTX001-131
First Submitted: December 20, 2019
First Posted: December 23, 2019
Last Update Posted: November 22, 2024
Last Verified: September 2024
History of Changes

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Study Description

Not Provided
Condition or Disease Intervention/Treatment
  • Beta-Thalassemia
  • Thalassemia
  • Sickle Cell Disease
  • Hematologic Diseases
  • Hemoglobinopathies
  • Genetic Diseases, Inborn
  • Sickle Cell Anemia
  • Biological: CTX001

Study Design

Study TypeInterventional
Anticipated Enrollment160 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeOther
Official TitleA Long-term Follow-up Study of Subjects With β-thalassemia or Sickle Cell Disease Treated With Autologous CRISPR-Cas9 Modified Hematopoietic Stem Cells (CTX001)
Study Start DateJanuary 20, 2021
Anticipated Primary Completion DateSeptember 2039
Anticipated Study Completion DateSeptember 2039

Groups and Cohorts

Group/ CohortIntervention/ Treatment
  • CTX001
    • All participants who complete or discontinue one of the multiple parent studies (CTX001-111, CTX001-121, CTX001-141, CTX001-151, CTX001-161 and CTX001-171) after CTX001 infusion will be asked to participate in this long-term follow-up study.
  • Biological: CTX001
    • CTX001 infusion.

Outcome Measures

Primary Outcome Measures

  1. New malignancies [Signing of informed consent up to 15 years post CTX001 infusion]
  2. New or worsening hematologic disorders [Signing of informed consent up to 15 years post CTX001 infusion]
  3. All-cause mortality [Signing of informed consent up to 15 years post CTX001 infusion]
  4. Serious adverse events (SAEs) [Signing of informed consent up to 15 years post CTX001 infusion]
  5. CTX001-related adverse events (AEs) [Signing of informed consent up to 15 years post CTX001 infusion]

Secondary Outcome Measures

  1. TDT and SCD: Total Hemoglobin (Hb) concentration over time [Up to 15 years post CTX001 infusion]
  2. TDT and SCD: Fetal Hemoglobin (HbF) concentration over time [Up to 15 years post CTX001 infusion]
  3. TDT and SCD: Proportion of alleles with intended genetic modification present in peripheral blood over time [Up to 15 years post CTX001 infusion]
  4. TDT and SCD: Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time [Up to 15 years post CTX001 infusion]
  5. TDT and SCD: Change in patient-reported outcome (PRO) over time in participants ≥18 years of age assessed using EuroQol quality of life scale (EQ-5D-5L) for participants from study 111,121 and 171 only [Up to 5 years post CTX001 infusion]
  6. TDT and SCD: Change in PROs over time in participants ≥18 years of age assessed using functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) questionnaire for participants from study 111, 121, 161 and 171 only [Up to 5 years post CTX001 infusion]
  7. TDT and SCD: Change in PROs over time in participants <18 years assessed using EQ-5D-Youth (EQ-5D-Y) from study 111,121,141,151 and 171 only [Up to 5 years post CTX001 infusion]
  8. TDT and SCD: Change in PROs over time in participants <18 years assessed using pediatric quality of life inventory (PedsQL) Core [Up to 5 years post CTX001 infusion]
  9. TDT: Proportion of participants achieving transfusion independence for at least 12 consecutive months (TI12) [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
  10. TDT: Proportion of participants achieving transfusion independence for at least 6 consecutive months (TI6) [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
  11. TDT: Proportion of participants achieving at least 95%, 90%, 85%, 75%, 50% reduction from baseline in annualized transfusions starting 60 days after CTX001 infusion [From Day 60 up to 15 years post-CTX001 infusion]
  12. TDT: Duration of transfusion free in participants who have achieved TI12 [From 60 days after last RBC transfusion up to 15 years post CTX001 infusion]
  13. TDT: Relative reduction from baseline in annualized volume of RBC transfusions [From Day 60 up to 15 years post-CTX001 infusion]
  14. TDT: Iron overload as measured by liver iron concentration (LIC), cardiac iron concentration (CIC), and ferritin for beta-Thalassemia participants [From Up to 5 years post CTX001 infusion (for LIC and CIC) and up to 15 years post CTX001 infusion (for ferritin)]]
  15. TDT: Proportion of participants receiving iron chelation therapy over time [Up to 15 years post CTX001 infusion]
  16. SCD: Proportion of participants who have not experienced any severe vaso-occlusive crises (VOC) for at least 12 consecutive months (VF12) [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
  17. SCD: Proportion of participants with SCD free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12) [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
  18. SCD: Proportion of participants with at least 90 percent (%), 80%, 75% or 50% reduction in annualized rate of severe VOCs [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
  19. SCD: Relative change from baseline in annualized rate of severe VOCs [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
  20. SCD: Duration of severe VOC free in participants who have achieved VF12 [From 60 days after last RBC transfusion up to 15 years post CTX001 infusion]
  21. SCD: Relative change from baseline in rate of inpatient hospitalizations for severe VOCs [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
  22. SCD: Relative change from baseline in annualized duration of hospitalization for severe VOCs [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
  23. SCD: Proportion of participants with sustained HbF ≥20% for at least 3 months [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
  24. SCD: Proportion of participants with sustained HbF ≥20% for at least 6 months [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
  25. SCD: Proportion of participants with sustained HbF ≥20% for at least 12 months [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
  26. SCD: Change in volume of RBCs transfused for SCD-related indications over time [Up to 15 years post CTX001 infusion]
  27. SCD: Change from baseline in reticulocytes/erythrocytes over time [From baseline up to 15 years post CTX001 infusion]
  28. SCD: Change from baseline in lactate dehydrogenase (LDH) over time [From baseline up to 15 years post CTX001 infusion]
  29. SCD: Change from baseline in haptoglobin over time [From baseline up to 15 years post CTX001 infusion]
  30. SCD: Change from baseline in total bilirubin over time [From baseline up to 15 years post CTX001 infusion]
  31. SCD: Change from baseline in indirect bilirubin over time [From baseline up to 15 years post CTX001 infusion]
  32. SCD: Change in SCD-specific PROs over time in participants ≥18 years of age assessed using adult sickle cell quality of life measurement system (ASCQ-Me) (participants from Study 121,161 and 171 only) [Up to 5 years post CTX001 infusion]
  33. SCD: Change in SCD-specific PROs over time in participants <18 years of age assessed using PedsQL Generic Core SCD module from studies 111,121,141,151,161 and 171 [Up to 5 years post CTX001 infusion]
  34. SCD: Change in PRO over time assessed using 11-point numerical rating scale (NRS) [Up to 5 years post CTX001 infusion]
  35. SCD: Change in PROs over time assessed using Wong Baker FACES pain scale [Up to 5 years post CTX001 infusion]
  36. SCD: Change in PROs over time using face, legs, activity, cry, consolability (FLACC) behavioral pain scale [Up to 5 years post CTX001 infusion]

Eligibility Criteria

Ages Eligible for Study 2 Years and Older (Child, Adult, Older Adult)
Sexes Eligible for Study All
Accepts Healthy Volunteers No
Inclusion Criteria
  • Participants (or his or her legally appointed and authorized representative or guardian) must sign and date informed consent form (ICF) and, where applicable, an assent form
  • Participants must have received CTX001 infusion in a parent study
Exclusion Criteria
  • There are no exclusion criteria

Contacts and Locations

Sponsors and Collaborators Vertex Pharmaceuticals Incorporated, CRISPR Therapeutics
CRISPR Therapeutics
Locations
  • Lucile Packard Children's Hospital | Palo Alto, California, United States, 94304
  • Ann & Robert Lurie Children's Hospital of Chicago | Chicago, Illinois, United States, 60611
  • Columbia University Medical Center (21+ years) | New York, New York, United States, 10032
  • Columbia University Medical Center | New York, New York, United States, 10032
  • Atrium Health Levine Children's Hospital | Charlotte, North Carolina, United States, 28203
  • Children's Hospital of Philadelphia | Philadelphia, Pennsylvania, United States, 19104
  • St. Jude Children's Research Hospital | Memphis, Tennessee, United States, 38105
  • The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers | Nashville, Tennessee, United States, 37203
  • Methodist Healthcare System of San Antonio, Methodist Hospital, Methodist Children's Hospital | San Antonio, Texas, United States, 78229
  • Hopital Universitaire des Enfants Reine Fabiola (HUDERF) | Brussels, Belgium,
  • The Hospital for Sick Children | Toronto, Canada,
  • Toronto General Hospital, University Health Network | Toronto, Canada,
  • St. Paul's Hospital | Vancouver, Canada,
  • University Hospital Duesseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology | Dusseldorf, Germany,
  • Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine | Regensburg, Germany,
  • University Hospital Tuebingen | Tuebingen, Germany,
  • Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCS | Rome, Italy,
  • Imperial College Healthcare NHS Trust, Hammersmith Hospital | London, United Kingdom,
  • University College London Hospitals NHS Foundation Trust | London, United Kingdom,

More Information

Additional Relevant MeSH Terms

  • Anemia, Sickle Cell
  • Thalassemia
  • beta-Thalassemia
  • Hematologic Diseases
  • Hemoglobinopathies
  • Genetic Diseases, Inborn
  • Anemia, Hemolytic, Congenital
  • Anemia, Hemolytic
  • Anemia