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: July 23, 2020
• Sponsor: Vertex Pharmaceuticals Incorporated
• Collaborator: CRISPR Therapeutics
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

Tracking Information

• First Submitted Date: December 20, 2019
• First Posted Date: December 23, 2019
• Last Update Posted Date: July 23, 2020
• Estimated Study Start Date: February 2021
• Estimated Primary Completion Date: September 2039 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 20, 2019)

• New malignancies [ Time Frame: Signing of informed consent up to 15 years post CTX001 infusion ]
• New or worsening hematologic disorders [ Time Frame: Signing of informed consent up to 15 years post CTX001 infusion ]
• All-cause mortality [ Time Frame: Signing of informed consent up to 15 years post CTX001 infusion ]
• 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 ]
• CTX001-related AEs [ Time Frame: Signing of informed consent up to 15 years post CTX001 infusion ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 20, 2019)

• Hemoglobin (Hb) concentration over time [ Time Frame: From Day 1 up to 15 years post CTX001 infusion ]
• HbF concentration over time [ Time Frame: From Day 1 up to 15 years post CTX001 infusion ]
• Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time [ Time Frame: From Day 1 up to 15 years post CTX001 infusion ]
• Transfusion dependent thalassemia (TDT) related transfusions for beta-Thalassemia subjects [ Time Frame: Signing of informed consent up to 15 years post CTX001 infusion ]
• Iron overload as measured by liver iron concentration (LIC), cardiac iron concentration (CIC), and ferritin for beta-Thalassemia subjects [ Time Frame: From Day 1 up to 5 years post CTX001 infusion (for LIC and CIC) and up to 15 years post CTX001 infusion (for ferritin) ]
• Proportion of subjects receiving iron chelation therapy over time [ Time Frame: From Day 1 up to 15 years post CTX001 infusion ]
• Annualized rate of severe vaso-occlusive crises (VOC) events for severe sickle cell disease (SCD) subjects [ Time Frame: From Day 1 up to 15 years post CTX001 infusion ]
• Sickle cell disease (SCD) related transfusions for SCD subjects [ Time Frame: From Day 1 up to 15 years post CTX001 infusion ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Long-term Follow-up Study in Subjects Who Received CTX001
• 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)
• 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 Study CTX001-121 (NCT03745287).
• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: All subjects who complete or discontinue the parent study (CTX001-111 or CTX001-121) after CTX001 infusion will be enrolled in the long-term follow-up study.

Condition

• Beta-Thalassemia
• Thalassemia
• Sickle Cell Disease
• Hematologic Diseases
• Hemoglobinopathies
• Genetic Diseases, Inborn
• Sickle Cell Anemia

Intervention

Biological: CTX001

CTX001 infusion

Study Groups/Cohorts

CTX001

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

Intervention: Biological: CTX001

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: December 20, 2019): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2039
• Estimated Primary Completion Date: September 2039 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subjects or legal representative or guardian (if applicable) must sign and date informed consent form (ICF)
• Subjects must have received CTX001 infusion

Exclusion Criteria:

• There are no exclusion criteria

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Italy, United States

Administrative Information

• NCT Number: NCT04208529
• Other Study ID Numbers: CTX001-131; 2018-002935-88 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

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

• Responsible Party: Vertex Pharmaceuticals Incorporated
• Study Sponsor: Vertex Pharmaceuticals Incorporated
• Collaborators: CRISPR Therapeutics
• Investigators: Not Provided
• PRS Account: Vertex Pharmaceuticals Incorporated
• Verification Date: February 2020