Clinical trial NCT06951867: Tezspire Cardiac Events PASS
Official title: An Observational Multi-Country Post-Authorisation Safety Study to Evaluate the Risk of Serious Adverse Cardiovascular Events in Adolescent and Adult Patients With Severe Asthma Taking Tezepelumab
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Cardiovascular Events
MACE
Keywords: post Marketing Requirements (PMR) study
cardiovascular events
non-fatal myocardial infarction
non-fatal stroke
cardiovascular death
arrythmias
coronary artery disease
heart failure
myocardial disorders
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: IQVIA Pvt. Ltd
First posted: 2025-04-30
Enrollment: 95574
Sex: ALL
Minimum age (years): 12
Maximum age (years): 130
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will be conducted using data sources from Denmark, France, Germany, and the United States of America (USA).

The source population will consist of patients with a diagnosis of asthma receiving tezepelumab or high-intensity SOC treatment for severe asthma at any point during the study inclusion period. From this source population, the exposed study population (i.e. patients who initiate tezepelumab treatment) and the unexposed study population (i.e. comparable patients who are unexposed to tezepelumab) will be identified.

Brief summary: The aim of this study is to evaluate the risk of serious adverse cardiovascular events in adolescent and adult patients with severe asthma taking tezepelumab compared to a population receiving standard of care treatment for severe asthma.

Detailed description: Tezepelumab (brand name: TEZSPIRE®), a human monoclonal antibody specific for the epithelial cell-derived cytokine thymic stromal lymphopoietin (TSLP), was recently launched as a first-in-class biologic add on treatment for patients with severe asthma. Results from DESTINATION, a long-term extension, phase 3 trial, showed a numeric imbalance in the occurrence of cardiac disorder system organ class serious adverse events (SAEs) in participants receiving tezepelumab compared to placebo. The observed imbalance resulted in the inclusion of serious cardiovascular events as an important potential risk to be addressed in the European Union (EU) risk management plan (RMP). AstraZeneca proposed to evaluate the risk of serious cardiovascular events with long-term tezepelumab treatment to meet regulatory requirements under a category 3 Post-Authorisation Safety Study (PASS).

This study is a non-interventional, longitudinal, population-based cohort study, using secondary data derived from multiple data sources. The study will consist of descriptive and a prevalent new-user design for comparative analyses of serious cardiovascular events outcomes in adolescent and adult patients with severe asthma exposed and unexposed to tezepelumab.

The study will be conducted using data sources from Denmark, France, Germany, and the United States of America (USA). The start of the study period will correspond to tezepelumab market launch date in each country of interest (i.e. between Q1 2022 - Q3 2023). An approximately five-year study period is planned in each country, with an anticipated last date of study period on 28 February 2029.

Eligibility criteria: Inclusion Criteria:

* patients with a diagnosis of asthma receiving tezepelumab or high-intensity SOC treatment for severe asthma at any point during the study inclusion period.

Exclusion Criteria for both exposed and unexposed groups include:

* \<12 months of data availability prior to index date,
* age \<12 years at index date,
* history of congenital heart disease or heart transplant outcome-specific exclusion criterion applied for each objective will include the presence of non-fatal myocardial infarction or stroke and the specific outcome of interest in the 180 days prior to index date
* for comparative analysis, an additional exclusion criterion will be considered, i.e. exposure to non-tezepelumab biologics on index date or within the 5-half-life clearance period of the biologic
* matching criteria (including, among other variables, the type and duration of SOC exposure in the 12 months before index date and propensity score \[PS\] matching) will be applied to ensure exposed and unexposed patients' comparability

Primary outcomes:
measure: composite outcome MACE
timeFrame: five years from tezepelumab market launch
Secondary outcomes:
measure: composite of four serious adverse cardiovascular events
timeFrame: five years from tezepelumab market launch
Other outcomes:
Locations:
Study officials:
affiliation: Iqvia Pty Ltd
name: Peter Egger
role: PRINCIPAL_INVESTIGATOR
References: