exagamglogene autotemcel (CTX001) for Transfusion-dependent beta thalassemia

Inclusion criteria

• {"criterion_text":"- Diagnosis of TDT as defined by: a. Documented homozygous or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Participants can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning. b. History of at least 100 mL/kilograms (kg)/year of packed RBC transfusions in the prior 24 months before signing of consent (or the last rescreening for patients going through repeat screening) or, for participants initiating transfusion therapy <24 months before signing of consent, requirement for packed RBC transfusion at least every 3 to 4 weeks for ≥6 months.\n- Eligible for autologous stem cell transplant as per investigator's judgment."}

Exclusion criteria

• {"criterion_text":"- A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor is available per investigator's judgement\n- Prior hematopoietic stem cell transplant (HSCT)\n- Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications\n- Participants with sickle cell β-thalassemia variant\n- Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator\n- Other protocol defined Inclusion/Exclusion criteria may apply."}

Primary endpoints

• {"endpoint_text":"- Proportion of subjects who achieve TI12. A subject will be considered to have achieved TI12 if he/she has maintained 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.","definition_or_measurement_approach":"TI12 defined as weighted average hemoglobin ≥9 g/dL without RBC transfusions for at least 12 consecutive months any time after CTX001 infusion; evaluation of TI12 begins 60 days after last RBC transfusion for post-transplant support or disease management."}

Secondary endpoints

• {"endpoint_text":"- Proportion of Participants Achieving at Least 95 Percent (%), 90%, 85%, 75% and 50% Reduction in Annualized Transfusions","definition_or_measurement_approach":"Proportion of participants achieving defined percentage reductions in annualized transfusion volume compared to baseline (annualized volume of RBC transfusions)."}
• {"endpoint_text":"- Relative Reduction in Annualized Volume of RBC Transfusions","definition_or_measurement_approach":"Measurement of change in annualized volume of RBC transfusions compared to baseline."}
• {"endpoint_text":"- Transfusion Free Duration for Participants who Achieve TI12","definition_or_measurement_approach":"Duration (time) participants remain free of RBC transfusions following achievement of TI12."}
• {"endpoint_text":"- Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time","definition_or_measurement_approach":"Proportion of alleles carrying the intended genetic modification measured in peripheral blood over time (genetic assay/timepoints)."}
• {"endpoint_text":"- Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time","definition_or_measurement_approach":"Proportion of alleles carrying the intended genetic modification measured in CD34+ bone marrow cells over time (genetic assay/timepoints)."}
• {"endpoint_text":"- HbF concentration (pre-transfusion) over time","definition_or_measurement_approach":"Fetal hemoglobin concentration measured pre-transfusion at specified timepoints over the study period."}
• {"endpoint_text":"- Total hemoglobin concentration (pre-transfusion) over time.","definition_or_measurement_approach":"Total hemoglobin concentration measured pre-transfusion at specified timepoints over the study period."}
• {"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":"Safety assessed by collection and analysis of adverse events, laboratory values, vital signs, neutrophil and platelet engraftment metrics, transplant-related mortality, and all-cause mortality."}
• {"endpoint_text":"- Proportion of subjects who achieve TI6. A subject will be considered to have achieved TI6 if he/she has maintained 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.","definition_or_measurement_approach":"TI6 defined as weighted average hemoglobin ≥9 g/dL without RBC transfusions for at least 6 consecutive months any time after CTX001 infusion; evaluation of TI6 begins 60 days after last RBC transfusion for post-transplant support or disease management."}

Germany

Earliest CTIS Part Ii Submission Date

18-11-2024

Latest Decision Or Authorization Date

25-11-2024

Processing Time Days

7

Number Of Sites

1

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

18-11-2024

Latest Decision Or Authorization Date

14-01-2025

Processing Time Days

57

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Vertex Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States