A Phase 2a Study of DP 2 -antagonist GB001 for Asthma.

BACKGROUND: GB001, a DP2 antagonist, may inhibit recruitment and activation of inflammatory cells in patients with asthma, consequently reducing airway inflammation. OBJECTIVE: Explore the efficacy and safety of GB001 in adults with mild to moderate asthma. METHODS: During a 4-week run-in period, adult patients with asthma (N = 158) received medium-dose inhaled corticosteroid and placebo and were then randomized to treatment once daily with GB001 5 mg, 20 mg, or placebo for 16 weeks or until asthma worsening/exacerbation. Patients were tapered to and then discontinued from low-dose inhaled corticosteroid at randomization and at 4 weeks postrandomization, respectively. Primary end point was change in morning peak expiratory flow (AM PEF); secondary end points included measures of asthma control. Safety was also assessed. RESULTS: Baseline characteristics were similar among GB001 5 mg, 20 mg, and placebo groups. Changes in AM PEF in 5 mg and 20 mg groups versus placebo showed mean differences (95% CI) of 15.2 (3.1-27.4) L/min (P = .02) and 13.7 (1.5-25.8) L/min (P = .03), respectively. The changes in forced expiratory volume in 1 second of 55 mL and 32 mL, respectively, were not significant. There was a significant difference between GB001 20 mg and placebo for the secondary end points of time to asthma worsening/exacerbation (hazard ratio, 0.29), 5-item Asthma Control Questionnaire score (-0.60 point), the percentage of days without asthma symptoms (26%), and the percentage of rescue-free days (22%). Patients with baseline eosinophil levels greater than or equal to 300/mL had larger differences between GB001 20 mg and placebo for changes in AM PEF. Similar effects were seen in a post hoc analysis for time to worsening/exacerbations and 5-item Asthma Control Questionnaire score. The most common nonserious adverse event in the GB001 groups compared with the placebo group was nasopharyngitis. CONCLUSIONS: GB001 was well tolerated and although not associated with clinically meaningful changes in lung function, improvements in asthma worsening/exacerbations and markers of asthma control were demonstrated. In addition, greater treatment effects were observed in patients with high baseline blood eosinophils. Further studies are needed to confirm these findings in the context of standard of care treatment. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.