A randomised, placebo-controlled trial of anti-interleukin-1 receptor 1 monoclonal antibody MEDI8968 in chronic obstructive pulmonary disease.
| Autor: | Calverley PMA; School of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK. pmacal@liverpool.ac.uk.; Clinical Science Centre, University Hospital Aintree, Longmoor Lane, Liverpool, L9 7AL, UK. pmacal@liverpool.ac.uk., Sethi S; Division of Pulmonary, Critical Care and Sleep Medicine, University of Buffalo, State University of New York, Buffalo, NY, USA., Dawson M; MedImmune, Cambridge, UK., Ward CK; MedImmmune, Gaithersburg, MD, USA.; Present address: Bristol-Myers Squibb, Princeton, NJ, USA., Finch DK; MedImmune, Cambridge, UK., Penney M; MedImmune, Cambridge, UK.; Present address: UCB Pharma, Slough, UK., Newbold P; MedImmmune, Gaithersburg, MD, USA., van der Merwe R; MedImmune, Cambridge, UK. |
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| Jazyk: | angličtina |
| Zdroj: | Respiratory research [Respir Res] 2017 Aug 09; Vol. 18 (1), pp. 153. Date of Electronic Publication: 2017 Aug 09. |
| DOI: | 10.1186/s12931-017-0633-7 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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