Long-term registry-based study of patients with transfusion-dependent β-thalassemia (TDT) or sickle cell disease (SCD) treated with exagamglogene autotemcel (exa-cel)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  CASGEVY
• Study drug International non-proprietary name (INN) or common name:
  EXAGAMGLOGENE AUTOTEMCEL
• Anatomical Therapeutic Chemical (ATC) code:
  (B06AX05) exagamglogene autotemcel

  exagamglogene autotemcel
• Medical condition to be studied:
  Sickle cell disease

  Thalassaemia beta

Population studied

• Short description of the study population:
  Patients with TDT or SCD treated in participating transplant centers reporting data to EBMT or CIBMTR Registry and receiving Casgevy or allogeneic-HSCT.
• Age groups:
  • Adolescents (12 to < 18 years)
  • Adults (18 to < 65 years)
• Estimated number of subjects:
  800

Study design details

• Study design:
  Long-term, prospective observational cohort study using primary and secondary data collected by established international hematopoietic stem cell transplant (HSCT) registries.
• Main study objective:
  1. Evaluate long-term safety outcomes in patients who received exa-cel for treatment of TDT or SCD ; 2. Evaluate long-term safety outcomes in patients who received exa-cel for treatment of TDT or SCD in comparison to patients receiving allo-HSCT;
• Setting:
  This is a study conducted in a real-world setting using primary and secondary data collected from the EBMT and CIBMTR patient registries; all transplant centers participating in this study will report data directly to their respective transplant registry. The study will include patients from Germany, France, Italy, UK, and US.
• Comparators:
  To be eligible for inclusion, comparators must be: ; • receiving an HSCT from a study-participating transplant center reporting data to the respective transplant registry; and; • receiving allo-HSCT for treatment of TDT or SCD from the date of approval of exa-cel through the end of the enrollment period; • Of an age that corresponds with the exa cel label current at the time of transplant.; ; All patients must additionally provide informed consent / assent for registry / study data collection. ; ;
• Outcomes:
  Safety outcomes: Neutrophil recovery, Platelet recovery, New malignancy, New or worsening hematologic disorder, Mortality ; Effectiveness Outcomes: Hemoglobin measures, Iron concentration measures, Disease-related end-organ damage / dysfunction diagnoses, Disease-related therapies ; Other outcomes: Transplant-related complications, Additional laboratory measures, Pregnancy ;
• Data analysis plan:
  Descriptive statistics will be presented for all study endpoints. Cumulative incidence curves will be provided for select outcomes. ; Within the TDT and SCD Exa-cel Cohorts, comparisons of the post-transplant period to pre-transplant period will be performed, as appropriate. ; Between cohort results (TDT Exa-cel versus TDT Allo-HSCT; SCD Exa-cel versus SCD Allo-HSCT) will also be evaluated within each registry separately. ; Subgroup analyses will be performed by age group, genotype, and/or other patient characteristics, as appropriate. Subgroup analyses by country of transplant may be performed if sufficient patient counts are available to preserve patient anonymity. Additional ad hoc statistical analyses may be implemented, as applicable (e.g., modeling to adjust for differences in cohort characteristics in between-cohort analyses, time-to-event analyses for select outcomes). Pooled analyses of key safety outcomes are planned at pre-specified timepoints (after 5-, 10-, and 15-year duration of follow-up is accrued for all enrolled patients).;