Novel CompEx Endpoint Could Improve Asthma Therapy Assessments

Because asthma exacerbations are intermittent, it can be a challenge to obtain enough subjects to properly assess the clinical effect of a treatment. A new study reveals that a novel endpoint for asthma, CompEx, could help determine the efficacy of an asthma therapy using smaller trial sizes and time periods.

CompEx, developed by AstraZeneca (AZ) in collaboration with researchers from the Universities of Colorado and Lund, combines deteriorations and frequency of asthma exacerbations that are recorded twice daily by patients. An algorithm is developed based off of patient deterioration below threshold limits and gradual deterioration over a five-day time frame.

The study, led by Göran Eriksson, Hendrick Nolte, and Christian Ljørring, Department of Respiratory Medicine at Lund University Hospital, Sweden, applied CompEx post-hoc to data from MITRA, a large phase 3 house dust mite (HDM) sublingual immunotherapy (SLIT) tablet allergic asthma trial.

During the trial, MITRA used an adapted version of the definition of moderate to severe asthma exacerbations established by the American Thoracic Society and the European Respiratory Society (ATS/ERS). Investigators wanted to compare results from CompEx to the results that implemented the ATS/ERS version (which was also modified to increase sensitivity in asthma trials).

In the MITRA trial, 834 participants were randomized to once-daily treatment of placebo or HDM SLIT tablet (6 SQ-HDM or 12 SQ-HDM). To qualify for the trial, candidates had to have a history of house dust mite allergic asthma for 1 year or more, associated rhinitis not controlled by inhaled corticosteroids (ICS), and positive tests for house dust mite sensitivity.

Participants kept a diary of data on peak expiratory flow, reliever use, and asthma symptoms, all documented each morning and evening, including nighttime awakenings, during the 6-month efficacy period.

Severe asthma exacerbations were defined as use of systemic corticosteroids or a hospital/emergency room visit due to asthma, as labeled by ATS/ERS. For CompEx, an exacerbation transpired when an ATS/ERS defined exacerbation occurred or when a diary event occurred.

At the three-month assessment, CompEx showed a 25% exacerbation rate with 12 SQ-HDM and placebo, compared to 19% with moderate/severe events. At the six-month assessment, CompEx still maintained a higher rate at 34%, versus 28% for moderate/severe events. Time to first event for 12 SQ-HDM and placebo was also evaluated, resulting in lower P values for CompEx when compared to moderate/severe events.

Overall, there was a 30% reduction in the number of patients needed per group for CompEx versus using the moderate/severe definition.

“The increased event rate after 3 months of ICS reduction combined with the lower p-values imply that using CompEx would allow conduct of an allergic asthma trial with a shorter duration or fewer subjects, while still maintaining statistical power,” investigators wrote.

The study, "Comparison of the novel CompEx asthma exacerbation endpoint to the ATS/ERS adapted moderate/severe asthma exacerbation definition used in the MITRA trial," was published online in Respiratory Journal.