Beta-Thalassemia, Genetic Diseases, Inborn, Hematologic Diseases, Hemoglobinopathies, Sickle Cell Anemia, Sickle Cell Disease, Thalassemia
Conditions
Brief summary
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).
Interventions
BIOLOGICALCTX001
CTX001 infusion.
Sponsors
Vertex Pharmaceuticals Incorporated
CRISPR Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Long Term Safety Follow-up
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 peripheral blood 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 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 |
| 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: 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: Duration of transfusion free in participants who have achieved TI12 | From 60 days after last RBC transfusion 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 |
| 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: 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 participants 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 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 |
| 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 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 |
| 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 |
Countries
Belgium, Canada, Germany, Italy, United Kingdom, United States
Outcome results
None listed