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

There were no significant changes from baseline (Visit 1) in plasma cytokine, sputum Th2 cytokine or sputum eosinophil levels in either the AZD8848 or placebo groups at 1 and 4 weeks after the last dose of AZD8848, with no significant difference between the groups. A trend towards a reduction in the sputum Th2 cytokines IL-5, IL-13 and in sputum eosinophils was observed 1 week after the last dose of AZD8848 compared with placebo prior to allergen challenge ( Fig. 5 ; p = 0.097, p = 0.054 and p = 0.068 respectively; Additional file 1: Table S1 and Figure S2 ). As expected, there was a robust Th2 cytokine response postallergen challenge in both the blood and sputum samples. However, there was no significant change from baseline in this response 1 week after cessation of dosing with AZD8848 or placebo. In addition, there appeared to be no differences in gene expression changes locally or systemically between the AZD8848 group and placebo group 1 week post-dosing before or after allergen challenge. In an allergen recall assay, 37 patients provided samples and the expected allergen-induced increase in Th2 cytokines (IL-5 and IL-13) was observed in PBMC prepared from the predose blood samples from the AZD8848 or placebo groups, with no significant increase in either IL-10 or IFNγ, indicating a good biomarker response in the house dust mitesensitive individuals. There was no significant change in this response observed 1 week post-dosing with either AZD8848 or placebo.