A phase 2a study of toreforant, a histamine H 4 receptor antagonist, in eosinophilic asthma.

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 (C) 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.