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 observed trend of both reduced IL-13 and reduced eosinophils, together with the pre-clinical results, suggest that TLR7 agonists may suppress the Th2 immune state in asthmatic subjects challenged with allergen. There were no changes in IFNregulated gene expression 1 week post-dosing in the current study, which is in keeping with previous clinical studies [24] . The lack of effect on PBMC response in the allergen recall experiment suggests that AZD8848 did not provide protection from the allergic inflammation induced by house dust mite allergen at 1 week post-dosing. The primary outcome variable for the allergen challenge test was the area under the curve (AUC). Power calculations for other endpoints were not performed, so the sample size was not based on a formal power calculation. Instead, a practical approach was used to obtain as many samples as feasible within the study. The absence of significant effects on the exploratory biomarkers studied at 1 week post-dosing indicates that there was no unwanted induction of systemic Th1 cytokines by administration of AZD8848. We did not design the study to assess upregulation of TRL7-mediated Th1 responses, but we have assumed that the inhibition of LAR observed here was due to this mechanism.