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CXCR2 antagonist for patients with chronic obstructive pulmonary disease with chronic mucus hypersecretion: a phase 2b trial.
In: Respiratory Research, Jg. 21 (2020-06-12), Heft 1, S. 1-10
Online
academicJournal
Zugriff:
Background: Oral CXC chemokine receptor 2 (CXCR2) antagonists have been shown to inhibit neutrophil migration and activation in the lung in preclinical and human models of neutrophilic airway inflammation. A previous study with danirixin, a reversible CXCR2 antagonist, demonstrated a trend for improved respiratory symptoms and health status in patients with COPD. Methods: This 26-week, randomised, double-blind, placebo-controlled phase IIb study enrolled symptomatic patients with mild-to-moderate COPD at risk for exacerbations. Patients received danirixin 5, 10, 25, 35 or 50 mg twice daily or placebo in addition to standard of care. Primary end-points were the dose response of danirixin compared with placebo on the incidence and severity of respiratory symptoms (Evaluating Respiratory Symptoms in COPD [E-RS:COPD] scores) and safety. Secondary end-points included the incidence of moderate-severe exacerbations, health status (COPD Assessment test, CAT) and health-related quality of life HRQoL (St. George Respiratory Questionnaire-COPD, SGRQ-C). Results: A total of 614 participants were randomized to treatment. There were no improvements in E-RS:COPD, CAT or SGRQ-C scores in participants treated with any dose of danirixin compared to placebo; a larger than expected placebo effect was observed. There was an increased incidence of exacerbation in the danirixin-treated groups and an increased number of pneumonias in participants treated with danirixin 50 mg. Conclusions: The robust placebo and study effects prohibited any conclusions on the efficacy of danirixin. However, the absence of a clear efficacy benefit and the observed increase in exacerbations in danirixin-treated groups suggests an unfavorable benefit-risk profile in patients with COPD. Trial Registration: This study was registered with clinicaltrials.gov, NCT03034967. [ABSTRACT FROM AUTHOR]
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CXCR2 antagonist for patients with chronic obstructive pulmonary disease with chronic mucus hypersecretion: a phase 2b trial.
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Autor/in / Beteiligte Person: | Lazaar, Aili L. ; Miller, Bruce E. ; Donald, Alison C. ; Keeley, Thomas ; Ambery, Claire ; Russell, John ; Watz, Henrik ; Tal-Singer, Ruth ; for 205724 Investigators ; Bardin, Philip ; Bremner, Peter ; Langton, David ; Southcott, Anne-Marie ; Thomas, Paul S. ; Wheatley, John ; Chapman, Kenneth R. ; Ferguson, Murdo ; Homik, Lawrence A. ; Maltais, Francois ; Pek, Bonavuth |
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Zeitschrift: | Respiratory Research, Jg. 21 (2020-06-12), Heft 1, S. 1-10 |
Veröffentlichung: | 2020 |
Medientyp: | academicJournal |
ISSN: | 1465-9921 (print) |
DOI: | 10.1186/s12931-020-01401-4 |
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