Effect of the CXCR2 antagonist danirixin on symptoms and health status in COPD

Approximately one-third of patients with chronic obstructive pulmonary disease (COPD) have chronic mucus hypersecretion (CMH) [1], often referred to as chronic bronchitis. Despite treatment with inhaled medications and other therapies such as expectorants or methylxanthines, patients with CMH may continue to experience exacerbations, substantial symptom burden and poor health status [1]. CXCR2 antagonists are effective in multiple preclinical and human models of airway inflammation [2–5]. Danirixin is a competitive, reversible oral CXCR2 antagonist that has been well-tolerated in healthy subjects and in patients with influenza [6, 7]. We report the results of a 52-week Phase 2 study conducted in Germany and the USA (GSK protocol 200163; ClinicalTrials.gov identifier [NCT02130193][1]) assessing the effects of danirixin when added to standard-of-care inhaled medications in participants with symptomatic COPD. Participants with an FEV1≥50% of predicted normal and a history of two exacerbations in the prior 12 months, or one exacerbation and elevated plasma fibrinogen ≥3 mg·mL−1, as well as a history of chronic cough and/or mucus hypersecretion on most days for at least the previous 3 months prior screening, were eligible. Full inclusion and exclusion criteria are available online at clinicaltrials.gov. The study was approved by the Western Institutional Review Board (Puyallup, WA, USA) and the Ethikkommission I, Arztekammer Schleswig-Holstein (Bad Segeberg, Germany). Written informed consent was obtained from all participants. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Lazaar is an employee of GlaxoSmithKline and holds stock in the company. Conflict of interest: Dr. Miller reports personal fees and other from GSK, during the conduct of the study. Conflict of interest: Dr. Yonchuk reports personal fees and other from GSK, during the conduct of the study. Conflict of interest: Dr. Leidy reports other from Evidera, during the conduct of the study; other from Evidera, outside the submitted work. Conflict of interest: Dr. Ambery reports other from GSK, during the conduct of the study. Conflict of interest: Dr. Bloomer reports personal fees and other from GSK, during the conduct of the study. Conflict of interest: Dr. Watz reports personal fees from GSK, during the conduct of the study. Conflict of interest: Ms. Tabberer is an employee of and holds stock in GSK. Conflict of interest: Dr. Tal-Singer reports personal fees and other from GSK, during the conduct of the study. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02130193&atom=%2Ferj%2Fearly%2F2018%2F08%2F16%2F13993003.01020-2018.atom