E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Sickle Cell Disease (SCD) |
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E.1.1.1 | Medical condition in easily understood language |
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 | 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 the efficacy of a single dose of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (CTX001) in pediatric subjects with severe sickle cell disease |
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E.2.2 | Secondary objectives of the trial |
• Evaluate the safety and tolerability of a single dose of CTX001 • Assess the effects of infusion of CTX001 on disease-specific events and clinical status • Quantify gene editing efficiency |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects 2 through 11 years of age, inclusive, on the date of informed consent • Diagnosis of severe sickle cell disease as defined by: • Documented severe sickle cell disease genotype • History of at least two severe vaso-occlusive crisis events per year for the previous two years prior to enrollment • Eligible for autologous stem cell transplant as per investigators judgment
Other protocol defined inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
• An available 10/10 human leukocyte antigen (HLA)-matched related donor • Prior hematopoietic stem cell transplant (HSCT) • Clinically significant and active bacterial, viral, fungal, or parasitic infection
Other protocol defined exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects who do not have any severe VOCs for at least 12 consecutive months (VF12) after CTX001 infusion. The evaluation of VF12 starts 60 days after the last RBC transfusion for post-transplant support or SCD disease management. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Safety and tolerability of CTX001 based on adverse events (AEs), clinical laboratory values, vital signs, neutrophil engraftment, platelet engraftment, transplant-related mortality (TRM), and all-cause mortality • Proportion of subjects free from inpatient hospitalization for severe VOCs for at least 12 months (HF12) after CTX001 infusion. The evaluation of HF12 starts 60 days after last RBC transfusion for post-transplant support or SCD disease management. • Relative reduction from baseline in annualized rate of severe VOCs up to 24 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for posttransplant support or SCD disease management. • Duration of severe VOC free in subjects who have achieved VF12 • Relative reduction from baseline in annualized rate of inpatient hospitalizations for severe VOCs up to 24 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management. • Relative reduction from baseline in annualized duration of hospitalization for severe VOCs up to 24 months 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. • Proportion of subjects with sustained HbF ≥30% 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. • Time for subjects to reach HbF ≥20% • Time for subjects to reach HbF ≥30% • Relative reduction from baseline in annualized volume of units of RBCs transfusions • HbF concentrations over time • Hb concentrations over time • Change in proportion of circulating erythrocytes expressing fetal hemoglobin (F-cells) over time • Change from baseline in reticulocyte count (percent reticulocytes and absolute reticulocyte count) over time • Change from baseline in indirect bilirubin over time • Change from baseline in haptoglobin over time • Time to first detectable haptoglobin post CTX001 infusion • Change from baseline in lactate dehydrogenase (LDH) over time • Time to first normalized LDH (defined as within normal range per local laboratory) post CTX001 infusion • 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
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 | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 |
United Kingdom |
United States |
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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The end of study is defined as the last scheduled visit (or contact) of the last subject, which is the date the last subject completes the 24-month follow-up period or date of early withdrawal from the study. |
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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 | 4 |
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 | 4 |
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 |