A Long-term Follow-up Study in Subjects Who Received CTX001

Sponsor
Vertex Pharmaceuticals Incorporated (Industry)
Overall Status
Enrolling by invitation
CT.gov ID
NCT04208529
Collaborator
CRISPR Therapeutics (Industry)
114
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9.5
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Study Details

Study Description

Brief Summary

This is a multi-site, observational study to evaluate the long-term safety and efficacy of CTX001 in subjects who received CTX001 in Study CTX001-111 (NCT03655678) or VX21-CTX001-141 (transfusion-dependent β-thalassemia [TDT] studies) or Study CTX001-121 (NCT03745287) or VX21-CTX001-151 (severe sickle cell disease [SCD] studies; NCT05329649).

Study Design

Study Type:
Observational
Anticipated Enrollment :
114 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
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)
Actual Study Start Date :
Jan 20, 2021
Anticipated Primary Completion Date :
Sep 1, 2039
Anticipated Study Completion Date :
Sep 1, 2039

Arms and Interventions

Arm Intervention/Treatment
CTX001

All subjects who complete or discontinue the parent study (CTX001-111 or CTX001-121 or VX21-CTX001-141 or VX21-CTX001-151) after CTX001 infusion will be asked to participate in this long-term follow-up study.

Biological: CTX001
CTX001 infusion.
Other Names:
  • Exagamglogene autotemcel
  • Exa-cel
  • 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) occurring up to 5 years after CTX001 infusion [Signing of informed consent up to 5 years post CTX001 infusion]

    5. CTX001-related AEs [Signing of informed consent up to 15 years post CTX001 infusion]

    Secondary Outcome Measures

    1. TDT and SCD: Hemoglobin (Hb) concentration over time [Up to 15 years post CTX001 infusion]

    2. TDT and SCD: 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: Change in patient-reported outcome (PRO) over time in subjects ≥18 years of age assessed using EuroQol quality of life scale (EQ-5D-5L) for subjects from study CTX001-111 and study CTX001-121 only [Up to 5 years post CTX001 infusion]

    5. TDT and SCD: Change in PROs over time in subjects ≥18 years of age assessed using functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) questionnaire for subjects from study CTX001-111 and study CTX001-121 only [Up to 5 years post CTX001 infusion]

    6. TDT and SCD: Change in PROs over time in subjects <18 years assessed using EQ-5D-Youth (EQ-5D-Y) [Up to 5 years post CTX001 infusion]

    7. TDT and SCD: Change in PROs over time in subjects <18 years assessed using pediatric quality of life inventory (PedsQL) Core [Up to 5 years post CTX001 infusion]

    8. TDT: Proportion of subjects achieving transfusion independence for at least 12 consecutive months (TI12) [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]

    9. TDT: Proportion of subjects achieving transfusion independence for at least 6 consecutive months (TI6) [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]

    10. TDT: Proportion of subjects 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]

    11. TDT: Duration of transfusion free in subjects who have achieved TI12 [From 60 days after last RBC transfusion up to 15 years post CTX001 infusion]

    12. TDT: Relative change from baseline in transfusions starting 60 days after CTX001 infusion [From Day 60 up to 15 years post-CTX001 infusion]

    13. TDT: Iron overload as measured by liver iron concentration (LIC), cardiac iron concentration (CIC), and ferritin for beta-Thalassemia subjects [From Up to 5 years post CTX001 infusion (for LIC and CIC) and up to 15 years post CTX001 infusion (for ferritin)]]

    14. TDT: Proportion of subjects receiving iron chelation therapy over time [Up to 15 years post CTX001 infusion]

    15. SCD: Proportion of subjects 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]

    16. SCD: Proportion of subjects 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]

    17. SCD: Proportion of subjects 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]

    18. 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]

    19. SCD: Duration of severe VOC free in subjects who have achieved VF12 [From 60 days after last RBC transfusion up to 15 years post CTX001 infusion]

    20. 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]

    21. 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]

    22. SCD: Proportion of subjects with sustained HbF ≥20% for at least 3 months [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]

    23. SCD: Proportion of subjects with sustained HbF ≥20% for at least 6 months [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]

    24. SCD: Proportion of subjects with sustained HbF ≥20% for at least 12 months [From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]

    25. SCD: Change in volume of RBCs transfused for SCD-related indications over time [Up to 15 years post CTX001 infusion]

    26. SCD: Change from baseline in reticulocytes/erythrocytes over time [From baseline up to 15 years post CTX001 infusion]

    27. SCD: Change from baseline in lactate dehydrogenase (LDH) over time [From baseline up to 15 years post CTX001 infusion]

    28. SCD: Change from baseline in haptoglobin over time [From baseline up to 15 years post CTX001 infusion]

    29. SCD: Change from baseline in total bilirubin over time [From baseline up to 15 years post CTX001 infusion]

    30. SCD: Change from baseline in indirect bilirubin over time [From baseline up to 15 years post CTX001 infusion]

    31. SCD: Change in SCD-specific PROs over time in subjects ≥18 years of age assessed using adult sickle cell quality of life measurement system (ASCQ-Me) (subjects from Study 121 only) [Up to 5 years post CTX001 infusion]

    32. SCD: Change in SCD-specific PROs over time in subjects <18 years of age assessed using PedsQL SCD module [Up to 5 years post CTX001 infusion]

    33. SCD: Change in PRO over time assessed using 11-point numerical rating scale (NRS) [Up to 5 years post CTX001 infusion]

    34. SCD: Change in PROs over time assessed using Wong Baker FACES pain scale [Up to 5 years post CTX001 infusion]

    35. 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

    Criteria

    Ages Eligible for Study:
    2 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Subjects (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

    • Subjects must have received CTX001 infusion in a parent study

    Exclusion Criteria:
    • There are no exclusion criteria

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Columbia University Medical Center (21+ years) New York New York United States 10032
    2 Columbia University Medical Center New York New York United States 10032
    3 St. Jude Children's Research Hospital Memphis Tennessee United States 38105
    4 The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers Nashville Tennessee United States 37203
    5 Methodist Healthcare System of San Antonio, Methodist Hospital, Methodist Children's Hospital San Antonio Texas United States 78229
    6 The Hospital for Sick Children Toronto Canada
    7 Toronto General Hospital, University Health Network Toronto Canada
    8 St. Paul's Hospital Vancouver Canada
    9 Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine Regensburg Germany
    10 Universitätsklinikum Tübingen Klinik für Kinder- und Jugendmedizin Tuebingen Germany
    11 Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCS Rome Italy
    12 Imperial College Healthcare NHS Trust, Hammersmith Hospital London United Kingdom

    Sponsors and Collaborators

    • Vertex Pharmaceuticals Incorporated
    • CRISPR Therapeutics

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Vertex Pharmaceuticals Incorporated
    ClinicalTrials.gov Identifier:
    NCT04208529
    Other Study ID Numbers:
    • CTX001-131
    • 2018-002935-88
    First Posted:
    Dec 23, 2019
    Last Update Posted:
    Jul 5, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Product Manufactured in and Exported from the U.S.:
    Yes
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 5, 2022