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

Study Overview
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Brief Summary
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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).

Official Title
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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)

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

Intervention / Treatment
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* Biological: CTX001


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CTX001<br>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<br>* CTX001 infusion.<br>* Other names: Exa-cel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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) occurring up to 5 years after CTX001 infusion |  | Signing of informed consent up to 5 years post CTX001 infusion | 
| CTX001-related AEs |  | Signing of informed consent up to 15 years post CTX001 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TDT and SCD: Hemoglobin (Hb) concentration over time |  | Up to 15 years post CTX001 infusion | 
| TDT and SCD: HbF concentration over time |  | Up to 15 years post CTX001 infusion | 
| TDT and SCD: Proportion of alleles with intended genetic modification present in peripheral blood over time |  | Up to 15 years post CTX001 infusion | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| TDT: Relative change from baseline in transfusions starting 60 days after CTX001 infusion |  | From Day 60 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 subjects |  | From Up to 5 years post CTX001 infusion (for LIC and CIC) and up to 15 years post CTX001 infusion (for ferritin)] | 
| TDT: Proportion of subjects receiving iron chelation therapy over time |  | Up to 15 years post CTX001 infusion | 
| 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 | 
| 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 | 
| 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 | 
| 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: 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 | 
| 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: 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 | 
| 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 | 
| 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 | 
| 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 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 | 
| 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 | 
| 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 |