RT Journal Article
SR Electronic
T1 Late-breaking abstract: Phase 2a randomized placebo-controlled trial of the oral prostaglandin D2 receptor (DP2/ CRTh2) antagonist QAW039 in eosinophilic asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2908
VO 44
IS Suppl 58
A1 Sherif Gonem
A1 Rachid Berair
A1 Amisha Singapuri
A1 Ruth Hartley
A1 Marie Laurencin
A1 Gerald Bacher
A1 Chengxing Lu
A1 Bjoern Holzhauer
A1 Michelle Bourne
A1 Vijay Mistry
A1 Ian Pavord
A1 Adel Mansur
A1 Andrew Wardlaw
A1 Salman Siddiqui
A1 Richard Kay
A1 Chris Brightling
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/2908.abstract
AB IntroductionThere is a high unmet need for safe, effective and convenient therapies to control symptoms and reduce the impact of exacerbations in severe asthma. Eosinophilic inflammation is common in asthma and attenuation of sputum eosinophilia is strongly associated with reduced exacerbation frequency.MethodsIn this single-center, double-blind, randomized controlled study, asthmatics (GINA II-V), with a sputum eosinophil count ≥2% at baseline, were randomised to QAW039 225mg BID or placebo for 12 weeks after a 2-week placebo run-in. The primary endpoint was the reduction of sputum eosinophils. Secondary, exploratory and post-hoc outcomes included changes in Asthma Control Questionnaire score (ACQ7), Asthma Quality of Life score (AQLQ) and FEV1.Results61 patients were randomized (30 to QAW039 and 31 to placebo); 90% were ≥GINA IV; and 25% were GINA V requiring up to 10 mg prednisolone daily. The primary endpoint was met, with QAW039 reducing sputum eosinophils 3.5-fold over placebo (95% CI: 1.7-7.0, p=0.001). The AQLQ improved in those treated with QAW039 compared to placebo (0.59 points; p=0.008) with non-significant improvements in ACQ7 in the group as a whole (0.40 points; p=0.084), which was greater in those with poor asthma control (ACQ≥1.5) at baseline (0.56 points; p=0.046). FEV1 improved in those receiving QAW039 versus placebo (0.074L; p=0.408; pre-bronchodilator (BD), 0.163L; p=0.022; post-BD). AEs were mild/moderate, balanced between both groups with no SAEs or deaths.ConclusionQAW039 is effective at attenuating eosinophilic airway inflammation, improves health status and lung function and has a favourable safety profile.