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

Name of medicine

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).