Exagamglogene autotemcel for Severe sickle cell disease | Sickle cell anaemia

Inclusion criteria

• {"criterion_text":"- Diagnosis of severe SCD as defined by: Documented SCD genotypes\n- History of at least two severe VOCs events per year for the previous two years prior to enrollment\n- Hydroxyurea (HU) failure unless HU intolerant\n- Eligible for autologous stem cell transplant as per investigators judgment"}

Exclusion criteria

• {"criterion_text":"- A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor\n- Prior hematopoietic stem cell transplant (HSCT)\n- Clinically significant and active bacterial, viral, fungal, or parasitic infection\n- Other protocol defined Inclusion/Exclusion criteria may apply"}

Primary endpoints

• {"endpoint_text":"- Proportion of subjects who do not have any severe vaso-occlusive crises (VOCs) for at least 12 consecutive months (VF12) after CTX001 infusion. The evaluation of VF12 starts 60 days after the last red blood cell (RBC) transfusion for post- transplant support or SCD disease management.","definition_or_measurement_approach":"VF12 is evaluated starting 60 days after the last RBC transfusion for post-transplant support or SCD disease management; primary endpoint is the proportion of subjects without any severe VOCs for at least 12 consecutive months after CTX001 infusion."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Assessed by monitoring adverse events, clinical laboratory values, vital signs, neutrophil and platelet engraftment, transplant-related mortality and all-cause mortality."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"HF12 evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management; proportion of subjects without inpatient hospitalization for severe VOCs for at least 12 months."}
• {"endpoint_text":"- 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 post-transplant support or SCD disease management","definition_or_measurement_approach":"Relative reduction from baseline in annualized rate of severe VOCs measured up to 24 months; evaluation starts 60 days after last RBC transfusion."}
• {"endpoint_text":"- Duration of severe VOC free in subjects who have achieved VF12.","definition_or_measurement_approach":"Duration (time) subjects remain free of severe VOCs following achievement of VF12."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Relative reduction from baseline in annualized inpatient hospitalization rate for severe VOCs up to 24 months; evaluation starts 60 days after last RBC transfusion."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Relative reduction from baseline in annualized duration (days) of hospitalization for severe VOCs up to 24 months; evaluation starts 60 days after last RBC transfusion."}
• {"endpoint_text":"- Proportion of subjects with sustained fetal hemoglobin (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","definition_or_measurement_approach":"Proportion of subjects with sustained HbF ≥20% for specified durations; evaluation starts 60 days after last RBC transfusion."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Proportion of subjects with sustained HbF ≥30% for specified durations; evaluation starts 60 days after last RBC transfusion."}
• {"endpoint_text":"- Time for subjects to reach HbF ≥20%","definition_or_measurement_approach":"Time-to-event: time from infusion to first occurrence of HbF ≥20%."}
• {"endpoint_text":"- Time for subjects to reach HbF ≥30%","definition_or_measurement_approach":"Time-to-event: time from infusion to first occurrence of HbF ≥30%."}
• {"endpoint_text":"- Relative reduction from baseline in annualized volume of RBC transfusions","definition_or_measurement_approach":"Relative reduction from baseline in annualized RBC transfusion volume measured over follow-up."}
• {"endpoint_text":"- HbF concentrations over time","definition_or_measurement_approach":"Serial measurement of fetal hemoglobin (HbF) concentrations over time."}
• {"endpoint_text":"- Hemoglobin (Hb) concentrations over time","definition_or_measurement_approach":"Serial measurement of hemoglobin concentrations over time."}
• {"endpoint_text":"- Change from baseline in reticulocyte count (percent reticulocytes and absolute reticulocyte count) over time","definition_or_measurement_approach":"Change from baseline in reticulocyte parameters measured longitudinally."}
• {"endpoint_text":"- Change from baseline in indirect bilirubin over time","definition_or_measurement_approach":"Change from baseline in indirect bilirubin measured longitudinally."}
• {"endpoint_text":"- Change from baseline in haptoglobin over time","definition_or_measurement_approach":"Change from baseline in haptoglobin measured longitudinally."}
• {"endpoint_text":"- Time to first detectable haptoglobin post CTX001 infusion","definition_or_measurement_approach":"Time-to-event: time from infusion to first detectable haptoglobin."}
• {"endpoint_text":"- Change from baseline in lactate dehydrogenase (LDH) over time","definition_or_measurement_approach":"Change from baseline in LDH measured longitudinally."}
• {"endpoint_text":"- Time to first normalized LDH (defined as within normal limits per local laboratory) post CTX001 infusion.","definition_or_measurement_approach":"Time-to-event: time from infusion to first LDH value within local laboratory normal limits."}
• {"endpoint_text":"- Proportion of alleles with intended genetic modification present in peripheral blood over time","definition_or_measurement_approach":"Molecular assay quantifying proportion of alleles with intended genetic modification in peripheral blood over time."}
• {"endpoint_text":"- Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time","definition_or_measurement_approach":"Molecular assay quantifying proportion of alleles with intended genetic modification in bone marrow CD34+ cells over time."}

Germany

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

04-06-2025

Processing Time Days

237

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

23-12-2025

Processing Time Days

439

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Vertex Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States