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

• ClinicalTrials.gov Identifier: NCT04208529
• Recruitment Status: Enrolling by invitation
• First Posted: December 23, 2019
• Last Update Posted: April 20, 2023
• Sponsor: Vertex Pharmaceuticals Incorporated
• Collaborator: CRISPR Therapeutics
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

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).

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 Type: Observational
• Estimated 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: January 20, 2021
• Estimated Primary Completion Date: September 2039
• Estimated Study Completion Date: September 2039

Groups and Cohorts

Group/Cohort	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 [ Time Frame: Signing of informed consent up to 15 years post CTX001 infusion ]
2. New or worsening hematologic disorders [ Time Frame: Signing of informed consent up to 15 years post CTX001 infusion ]
3. All-cause mortality [ Time Frame: Signing of informed consent up to 15 years post CTX001 infusion ]
4. Serious adverse events (SAEs) occurring up to 5 years after CTX001 infusion [ Time Frame: Signing of informed consent up to 5 years post CTX001 infusion ]
5. CTX001-related AEs [ Time Frame: Signing of informed consent up to 15 years post CTX001 infusion ]

Secondary Outcome Measures :

1. TDT and SCD: Hemoglobin (Hb) concentration over time [ Time Frame: Up to 15 years post CTX001 infusion ]
2. TDT and SCD: HbF concentration over time [ Time Frame: Up to 15 years post CTX001 infusion ]
3. TDT and SCD: Proportion of alleles with intended genetic modification present in peripheral blood over time [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Up to 5 years post CTX001 infusion ]
8. TDT: Proportion of subjects achieving transfusion independence for at least 12 consecutive months (TI12) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: From Day 60 up to 15 years post-CTX001 infusion ]
11. TDT: Duration of transfusion free in subjects who have achieved TI12 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 15 years post CTX001 infusion ]
26. SCD: Change from baseline in reticulocytes/erythrocytes over time [ Time Frame: From baseline up to 15 years post CTX001 infusion ]
27. SCD: Change from baseline in lactate dehydrogenase (LDH) over time [ Time Frame: From baseline up to 15 years post CTX001 infusion ]
28. SCD: Change from baseline in haptoglobin over time [ Time Frame: From baseline up to 15 years post CTX001 infusion ]
29. SCD: Change from baseline in total bilirubin over time [ Time Frame: From baseline up to 15 years post CTX001 infusion ]
30. SCD: Change from baseline in indirect bilirubin over time [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Up to 5 years post CTX001 infusion ]
33. SCD: Change in PRO over time assessed using 11-point numerical rating scale (NRS) [ Time Frame: Up to 5 years post CTX001 infusion ]
34. SCD: Change in PROs over time assessed using Wong Baker FACES pain scale [ Time Frame: Up to 5 years post CTX001 infusion ]
35. SCD: Change in PROs over time using face, legs, activity, cry, consolability (FLACC) behavioral pain scale [ Time Frame: 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
• Sampling Method: Non-Probability Sample

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.

Criteria

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

United States, New York

Columbia University Medical Center (21+ years)

New York, New York, United States, 10032

Columbia University Medical Center

New York, New York, United States, 10032

United States, North Carolina

Atrium Health Levine Children's Hospital

Charlotte, North Carolina, United States, 28203

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

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

United States, Texas

Methodist Healthcare System of San Antonio, Methodist Hospital, Methodist Children's Hospital

San Antonio, Texas, United States, 78229

Canada

The Hospital for Sick Children

Toronto, Canada

Toronto General Hospital, University Health Network

Toronto, Canada

St. Paul's Hospital

Vancouver, Canada

Germany

Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine

Regensburg, Germany

Universitätsklinikum Tübingen Klinik für Kinder- und Jugendmedizin

Tuebingen, Germany

Italy

Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCS

Rome, Italy

United Kingdom

Imperial College Healthcare NHS Trust, Hammersmith Hospital

London, United Kingdom

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

CRISPR Therapeutics

More Information

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT04208529
• Other Study ID Numbers: CTX001-131; 2018-002935-88 ( EudraCT Number )
• First Posted: December 23, 2019
• Last Update Posted: April 20, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

• Studies a U.S. FDA-regulated Drug Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

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