Effects of the Toll-like receptor 7 (TLR7) agonist, AZD8848, on allergen-induced responses in patients with mild asthma: a double-blind, randomised, parallel-group study

Leaker, Brian R.; Singh, Dave; Lindgren, Sam; Almqvist, Gun; Eriksson, Leif; Young, Barbara; O’Connor, Brian

The primary outcome variable was the area under the curve (AUC)-based average mean fall from the pre-dose value of FEV 1 during the 4-10 h interval post allergen assessment (LAR) at 1 week post-treatment. Serial measurements of FEV 1 were performed every 30 min. Data from the allergen challenges were summarized in terms of two mean FEV 1 values, both computed from an area under the curve (trapezoidal rule), divided by observational time. Data were analysed both as FEV 1 in litres and as percent change (in mean value) from the zero value, which was the first FEV 1 measurement at the same visit measured prior to the allergen challenge. An additional allergen challenge at 4 weeks post-treatment was used to assess duration of efficacy. Secondary outcomes included EAR, measured by the average fall in FEV 1 at 0-2 h post-allergen challenge; PC 20 methacholine challenge (the provocative concentration of methacholine causing a 20% fall in FEV 1 ) was used to assess allergen-induced AHR; analyses of biomarkers (including blood and sputum cytokines and cell counts) were carried out to explore the mechanism of action of AZD8848. Baseline biomarkers including blood and sputum eosinophils were assessed at visit 1 and again after treatment. Safety and tolerability were assessed by adverse events (AEs) and vital signs/electrocardiographic parameters.