Abstract
BACKGROUND: Interleukin-1 receptor 1 (IL-1R1) inhibition is a potential strategy for treating patients with chronic obstructive pulmonary disease (COPD). MEDI8968, a fully human monoclonal antibody, binds selectively to IL-1R1, inhibiting activation by IL-1α and IL-1β. We studied the efficacy and safety/tolerability of MEDI8968 in adults with symptomatic, moderate-to-very severe COPD. METHODS: This was a phase II, randomised, double-blind, placebo-controlled, multicentre, parallel-group study. Subjects aged 45-75 years and receiving standard maintenance therapy with ≥2 exacerbations in the past year were randomised 1:1 to receive placebo or MEDI8968 300 mg (600 mg intravenous loading dose) subcutaneously every 4 weeks, for 52 weeks. The primary endpoint was the moderate/severe acute exacerbations of COPD (AECOPD) rate (week 56 post-randomisation). Secondary endpoints were severe AECOPD rate and St George's Respiratory Questionnaire-COPD (SGRQ-C) score (week 56 post-randomisation). RESULTS: Of subjects randomised to placebo (n = 164) and MEDI8968 (n = 160), 79.3% and 75.0%, respectively, completed the study. There were neither statistically significant differences between treatment groups in moderate/severe AECOPD rate ([90% confidence interval]: 0.78 [0.63, 0.96], placebo; 0.71 [0.57, 0.90], MEDI8968), nor in severe AECOPD rate or SGRQ-C scores. Post-hoc analysis of subject subgroups (by baseline neutrophil count or tertiles of circulating neutrophil counts) did not alter the study outcome. The incidence of treatment-emergent adverse events (TEAEs) with placebo and MEDI8968 treatment was similar. The most common TEAE was worsening of COPD. CONCLUSIONS: In this phase II study, MEDI8968 did not produce statistically significant improvements in AECOPD rate, lung function or quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01448850 , date of registration: 06 October 2011.