A phase 2a study of toreforant, a histamine H4 receptor antagonist, in eosinophilic asthma

Abstract Background Data from preclinical and clinical studies support the evaluation of histamine 4 receptor antagonists in the treatment of asthma. Toreforant is a selective histamine 4 receptor antagonist that could be effective in patients with eosinophilic asthma. Objective To evaluate the efficacy and safety of toreforant in patients with eosinophilic, persistent asthma that was inadequately controlled despite current treatment. Methods In this phase 2a, multicenter, randomized, double-blinded, parallel-group, placebo-controlled, proof-of-concept study, 162 eligible patients were randomized (1:1) to placebo or 30 mg of toreforant once daily through week 24 and followed for 4 weeks. The primary end point was change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at week 16. Secondary end points included change from baseline at week 16 in postbronchodilator percent-predicted forced expiratory volume in 1 second, Asthma Control Questionnaire scores, weekly averages of Daytime and Nighttime Asthma Diary Symptom Scores, and weekly average of number of puffs in a day that rescue medication was used. Results There was no significant difference between groups in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at week 16 (difference in least-square means −0.19%; 95% confidence interval −3.01 to 2.64; P  = .90). Similarly, there were no significant differences between groups at week 16 in changes from baseline in the secondary end points ( P ≥ .30). Toreforant was generally well tolerated. No deaths or serious adverse events were reported at any time point. Conclusion Toreforant, at the dose tested, failed to provide therapeutic benefit in this population of patients with uncontrolled, eosinophilic, persistent asthma. Trial Registration ClinicalTrials.gov, NCT01823016