E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transfusion-dependent β thalassemia (TDT). Severe sickle cell disease (SCD). |
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E.1.1.1 | Medical condition in easily understood language |
Transfusion-dependent β thalassemia. Severe sickle cell disease. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 26.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043391 |
E.1.2 | Term | Thalassaemia beta |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040641 |
E.1.2 | Term | Sickle cell anaemia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate long-term safety up to 15 years after CTX001 infusion in subjects who received CTX001 for treatment of transfusion-dependent thalassemia (TDT) or severe sickle cell disease (SCD) |
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E.2.2 | Secondary objectives of the trial |
To evaluate efficacy of CTX001 up to 15 years after CTX001 infusion, in subjects who received CTX001 for treatment of TDT or severe SCD |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 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. 2. Subjects must have received CTX001 infusion in a parent study. |
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E.4 | Principal exclusion criteria |
1. There are no exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• New malignancies • New or worsening hematologic disorders (e.g. immune-mediated cytopenias, aplastic anemia, primary immunodeficiencies) • All-cause mortality • All serious adverse events (SAEs) • CTX001-related AEs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 15 years after CTX001 infusion |
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E.5.2 | Secondary end point(s) |
TDT and SCD: • Total Hemoglobin (Hb) concentration over time • Fetal hemoglobin (HbF) concentration over time • Proportion of alleles with intended genetic modification present in peripheral blood over time • Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time • Change in patient-reported outcomes (PROs) over time in subject ≥ 18 years of age using: o EuroQol Questionnaire – 5 dimensions – 5 levels of severity (EQ-5D-5L; subjects from Study 111 and Study 121, and Study 171 only) o Functional assessment of cancer therapy bone marrow transplant (FACT-BMT) (subjects from Study 111, Study 121, Study 161, and 171 only) • Change in PROs over time in subjects <18 years of age using: o EuroQol Questionnaire – 5 dimensions – youth (EQ-5D-Y; selfcomplete and proxy versions based on age; subjects from Study 111, Study 121, Study 141, Study 151^, and Study 171 only) o Pediatric Quality of Life Inventory (PedsQL) Genetic Core (self-complete and proxy versions based on age; all studies) TDT only: • Proportion of subjects achieving TI12, defined as maintaining weighted average Hb ≥9 g/dL without RBC transfusions for at least 12 consecutive months any time after CTX001 infusion. The evaluation of TI12 starts 60 days after last RBC transfusion for post-transplant support or TDT disease management. • Proportion of subjects achieving TI6, defined as maintaining weighted average Hb ≥9 g/dL without RBC transfusions for at least 6 consecutive months any time after CTX001 infusion. The evaluation of TI6 starts 60 days after last RBC transfusion for post-transplant support or TDT disease management. • Proportion of subjects achieving at least 95%, 90%, 85%, 75%, 50% reduction from baseline in annualized transfusions starting 60 days after CTX001 infusion. • Duration transfusion free in subjects who have achieved TI12 • Relative reduction from baseline in annualized volume of RBC transfusion • Iron overload as measured by liver iron concentration (LIC), cardiac iron concentration (CIC), and ferritin over time • Proportion of subjects receiving iron chelation therapy over time SCD only: • Proportion of subjects who have not experienced any severe VOC for at least 12 consecutive months (VF12) after CTX001 infusion. The evaluation of VF12 starts 60 days after last RBC transfusion for posttransplant support or SCD disease management • Proportion of subjects free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12) after CTX001 infusion. The evaluation of HF12 starts 60 days after last RBC transfusion for posttransplant support or SCD disease management • Proportion of subjects with reduction in annualized rate of severe VOCs at the time of analysis from baseline by at least 90%, 80%, 75%, 50% after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management • Relative change from baseline in annualized rate of severe VOCs after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management • Duration of severe VOC free in subjects who have achieved VF12 • Relative change from baseline in rate of inpatient hospitalizations for severe VOCs after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management • Relative change from baseline in annualized duration of hospitalization for severe VOCs after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management • Proportion of subjects with sustained HbF ≥20% at the time of analysis for at least 3 months, 6 months, or 12 months. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management • Change in volume of RBCs transfused for SCD-related indications over time • Change from baseline in hemolysis markers (reticulocytes/erythrocytes, lactate dehydrogenase [LDH], haptoglobin, total and indirect bilirubin) over time • Change in SCD-specific PROs over time in subjects ≥18 years of age using Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) (subjects from Study 121, Study 161, and Study 171 only) • Change in SCD-specific PROs over time in subjects <18 years of age using PedsQL SCD module (self-complete and proxy versions based on age) • Change in Pain Scale PROs (based on age) over time using Numeric Rating Scale (NRS) 11-point, Wong Baker FACES Pain Scale, or FLACC Behavioral Pain Scale |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 15 years after CTX001 infusion with exception of LIC, CIC and PROs (including Pain Scales) which will be assessed for up to 5 years. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 0 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
United Kingdom |
United States |
Belgium |
France |
Germany |
Italy |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 21 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 21 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |