Calverley, Peter MA, Sethi, Sanjay, Dawson, Michelle, Ward, Christine K, Finch, Donna K, Penney, Mark, Newbold, Paul and van der Merwe, Rene
(2017)
A randomised, placebo-controlled trial of anti-interleukin-1 receptor 1 monoclonal antibody MEDI8968 in chronic obstructive pulmonary disease.
RESPIRATORY RESEARCH, 18 (1).
153-.
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>In this phase II study, MEDI8968 did not produce statistically significant improvements in AECOPD rate, lung function or quality of life.<h4>Trial registration</h4>ClinicalTrials.gov, NCT01448850 , date of registration: 06 October 2011.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | C-reactive protein, COPD, Fibrinogen, Interleukin-1 receptor 1, MEDI8968, Neutrophils, Pharmacology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 17 Aug 2018 14:24 |
| Last Modified: | 25 May 2023 19:51 |
| DOI: | 10.1186/s12931-017-0633-7 |
| Open Access URL: | https://doi.org/10.1186/s12931-017-0633-7 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3025184 |
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