exagamglogene autotemcel for Transfusion-dependent beta-thalassemia | Severe sickle cell disease

Inclusion criteria

• {"criterion_text":"- Participants with TDT and SCD: Eligible for autologous stem cell transplant as per investigator's judgment.\n- Participants with TDT: Diagnosis of TDT as defined by: Documented homozygous β-thalassemia 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 History of at least 100 milliliter (mL)/kilograms (kg)/year or 10 units/year of packed red blood cells (RBC) transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening\n- Participants with SCD: Diagnosis of severe SCD as defined by: Documented SCD genotypes History of at least two severe VOCs events per year for the previous two years prior to enrollment"}

Exclusion criteria

• {"criterion_text":"- Participants with TDT and SCD: A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor is available per investigator's judgement Prior hematopoietic stem cell transplant (HSCT) Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator\n- Participants with TDT: Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications Participants with sickle cell β-thalassemia variant\n- Participants with SCD: History of untreated moyamoya syndrome or presence of moyamoya syndrome at screening"}

Primary endpoints

• {"endpoint_text":"- HbF and Hb levels over time. The evaluation will start 60 days after last RBC transfusion for post-transplant support or disease management.","definition_or_measurement_approach":"Serial measurement of HbF and haemoglobin (Hb) over time; evaluation window begins 60 days after last RBC transfusion for post-transplant support or disease management."}

Secondary endpoints

• {"endpoint_text":"- TDT and SCD: Safety and tolerability of CTX001 based on adverse events (AEs), clinical laboratory values, neutrophil engraftment, platelet engraftment, transplant-related mortality (TRM), and all-cause mortality.","definition_or_measurement_approach":"Safety assessed by recording AEs, lab values, neutrophil and platelet engraftment timing, transplant-related mortality and all-cause mortality."}
• {"endpoint_text":"- TDT and SCD: Relative reduction from baseline in annualized volume of RBC transfusions","definition_or_measurement_approach":"Compare annualized volume of RBC transfusions post-treatment versus baseline."}
• {"endpoint_text":"- TDT and SCD: Proportion of alleles with intended genetic modification present in peripheral blood over time","definition_or_measurement_approach":"Molecular assay measuring fraction of alleles with intended edit in peripheral blood samples over time."}
• {"endpoint_text":"- TDT and SCD: Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time","definition_or_measurement_approach":"Molecular assay measuring fraction of alleles with intended edit in bone marrow CD34+ cells over time."}
• {"endpoint_text":"- TDT: Duration transfusion free","definition_or_measurement_approach":"Time from treatment to first transfusion (duration transfusion-free period)."}
• {"endpoint_text":"- SCD: Relative reduction from baseline in annualized rate of severe vaso-occlusive crises (VOCs) up to 12 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":"Compare annualized rate of severe VOCs in the 12 months post-treatment versus baseline; evaluation window begins 60 days after last RBC transfusion."}
• {"endpoint_text":"- SCD: Relative reduction from baseline in annualized rate of inpatient hospitalizations for severe VOCs up to 12 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":"Compare annualized rate of inpatient hospitalizations for severe VOCs up to 12 months post-treatment versus baseline; evaluation starts 60 days after last RBC transfusion."}
• {"endpoint_text":"- SCD: Relative reduction from baseline in annualized duration of hospitalization for severe VOCs up to 12 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":"Compare annualized duration of hospitalization for severe VOCs up to 12 months post-treatment versus baseline; evaluation starts 60 days after last RBC transfusion."}
• {"endpoint_text":"- SCD: Relative reduction from baseline in markers of hemolysis up to 12 months after CTX001 infusion.","definition_or_measurement_approach":"Laboratory measures of hemolysis markers compared to baseline up to 12 months post-infusion."}

Germany

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

14-05-2025

Processing Time Days

350

Number Of Sites

1

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

16-05-2025

Processing Time Days

352

Number Of Sites

1

Number Of Participants

4

Primary sponsor

Full Name

Vertex Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States