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

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)

This is a multi-site, open- label rollover study to evaluate the long-term safety and efficacy of CTX001 in pediatric and adult participants who received CTX001 in parent studies 111 (NCT03655678) 141 (NCT05356195) or 161 (NCT05477563) (transfusion-dependent β-thalassemia [TDT] studies) or Study 121 (NCT03745287) or 151 (NCT05329649) or 161(NCT05477563) (severe sickle cell disease [SCD] studies).

Study Overview

• Status: Enrolling by invitation
• Conditions: Hematologic Diseases; Genetic Diseases, Inborn; Sickle Cell Disease; Hemoglobinopathies; Sickle Cell Anemia; Thalassemia; Beta-Thalassemia
• Intervention / Treatment: Biological: CTX001

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Hopital Universitaire des Enfants Reine Fabiola (HUDERF) - Hematology
• Canada
  • Toronto, Canada
    • Hospital for Sick Children - Hematology
  • Toronto, Canada
    • Toronto General Hospital - Hematology
  • Vancouver, Canada
    • St. Paul's Hospital - Hematology
• Germany
  • Düsseldorf, Germany
    • University Hospital Duesseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology
  • Klinik Für Kinder- Und Jugendmedizin, Germany
    • Center for Pediatric Clinical Studies (CPCS)
  • Regensburg, Germany
    • Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine
• Italy
  • Rome, Italy
    • IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica
• United Kingdom
  • London, United Kingdom
    • Great Ormond Street Hospital for Children
  • London, United Kingdom
    • Hammersmith Hospital - Haematology Dept
  • London, United Kingdom
    • University College London Hospital NHS Foundation - Main
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago - Hematology
  • New York
    • New York, New York, United States, 10032
      • Herbert Irving Pavilion - Hematology
    • New York, New York, United States, 10032
      • New York Presbyterian Hospital - Morgan Stanley Children's Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Levine Children's Hospital - Hematology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia - Hematology
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37203
      • TriStar Medical Group Children's Specialists - Pediatric Oncology
  • Texas
    • San Antonio, Texas, United States, 78229
      • Methodist Healthcare System of San Antonio, Methodist Hospital, Methodist Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

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 enrolled in the long-term follow-up study.

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTX001; All participants who complete or discontinue one of the multiple parent studies (CTX001-111, CTX001-121, CTX001-141, CTX001-151 and CTX001-161) 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
New malignancies	Signing of informed consent up to 15 years post CTX001 infusion
New or worsening hematologic disorders	Signing of informed consent up to 15 years post CTX001 infusion
All-cause mortality	Signing of informed consent up to 15 years post CTX001 infusion
Serious adverse events (SAEs)	Signing of informed consent up to 15 years post CTX001 infusion
CTX001-related adverse events (AEs)	Signing of informed consent up to 15 years post CTX001 infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
TDT and SCD: Proportion of alleles with intended genetic modification present in peripheral blood over time	Up to 15 years post CTX001 infusion
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
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
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
SCD: Change in volume of RBCs transfused for SCD-related indications over time	Up to 15 years post CTX001 infusion
SCD: Change from baseline in reticulocytes/erythrocytes over time	From baseline up to 15 years post CTX001 infusion
SCD: Change from baseline in lactate dehydrogenase (LDH) over time	From baseline up to 15 years post CTX001 infusion
SCD: Change from baseline in haptoglobin over time	From baseline up to 15 years post CTX001 infusion
SCD: Change from baseline in total bilirubin over time	From baseline up to 15 years post CTX001 infusion
SCD: Change from baseline in indirect bilirubin over time	From baseline up to 15 years post CTX001 infusion
SCD: Change in PRO over time assessed using 11-point numerical rating scale (NRS)	Up to 5 years post CTX001 infusion
SCD: Change in PROs over time assessed using Wong Baker FACES pain scale	Up to 5 years post CTX001 infusion
SCD: Change in PROs over time using face, legs, activity, cry, consolability (FLACC) behavioral pain scale	Up to 5 years post CTX001 infusion
TDT and SCD: Total Hemoglobin (Hb) concentration over time	Up to 15 years post CTX001 infusion
TDT and SCD: Fetal Hemoglobin (HbF) concentration over time	Up to 15 years post CTX001 infusion
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
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
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
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
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
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
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
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
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
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
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
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
TDT: Proportion of participants achieving at least 95%, 90%, 85%, 75%, 50% reduction from baseline in annualized volume of RBC transfusions starting after month 10 after CTX001 infusion for participants who have not achieved TI12	From Month 10 up to 15 years post-CTX001 infusion
TDT: Relative reduction from baseline in annualized volume of RBC transfusions starting after Month 10 after CTX001 infusion for participants who have not achieved TI12	From Month 10 up to 15 years post-CTX001 infusion
TDT: Iron overload as measured by liver iron concentration (LIC), cardiac iron concentration (CIC), and ferritin for beta-Thalassemia participants	Up to 8 years post CTX001 infusion for LIC; up to 5 years post CTX001 infusion for CIC and up to 15 years post CTX001 infusion for ferritin
TDT: Proportion of participants receiving iron removal therapy over time	Up to 15 years post CTX001 infusion
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 and 121 only	Up to 5 years post CTX001 infusion
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 and 161 only	Up to 5 years post CTX001 infusion
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 and 151 only	Up to 5 years post CTX001 infusion
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 and 161 only)	Up to 5 years post CTX001 infusion
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 and 161	Up to 5 years post CTX001 infusion

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated
• Collaborators: CRISPR Therapeutics

Publications and helpful links

General Publications

• Fuente J, Frangoul H, Lang P, Wall D, Meisel R, Corbacioglu S, Li AM, Shah AJ, Carpenter B, Kwiatkowski JL, Mapara MY, Liem RI, Rupprecht J, Kuo KHM, Merkeley H, Algeri M, Smith W, Kohli P, Li N, Rubin J, Zhang S, Hobbs W, Locatelli F. Improvements in health-related quality of life in patients with transfusion-dependent beta-thalassemia after exagamglogene autotemcel. Blood Adv. 2025 Dec 23;9(24):6502-6510. doi: 10.1182/bloodadvances.2025016702.
• Sharma A, Locatelli F, Bhatia M, Molinari L, Mapara MY, Liem RI, Dedeken L, Wall D, Eckrich MJ, Kuo KHM, Smith W, Imren S, Kohli P, Li N, Liu T, Rubin J, Hobbs W, Grupp SA, Frangoul H. Improvements in health-related quality of life in patients with severe sickle cell disease after exagamglogene autotemcel. Blood Adv. 2025 Dec 23;9(24):6481-6490. doi: 10.1182/bloodadvances.2025016701.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2021
• Primary Completion (Estimated): September 30, 2039
• Study Completion (Estimated): September 30, 2039

Study Registration Dates

• First Submitted: December 20, 2019
• First Submitted That Met QC Criteria: December 20, 2019
• First Posted (Actual): December 23, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Anemia, Sickle Cell; Thalassemia; beta-Thalassemia; Hematologic Diseases; Hemoglobinopathies; exagamglogene autotemcel
• Other Study ID Numbers: VX18-CTX001-131; 2024-512654-19-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/our-science/clinical-trials-data-sharing/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes