School of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
Clinical Science Centre, University Hospital Aintree, Longmoor Lane, Liverpool, L9 7AL, UK.
Respir Res. 2017 Aug 9;18(1):153. doi: 10.1186/s12931-017-0633-7.
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.
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).
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.
In this phase II study, MEDI8968 did not produce statistically significant improvements in AECOPD rate, lung function or quality of life.
ClinicalTrials.gov, NCT01448850 , date of registration: 06 October 2011.
白细胞介素-1 受体 1（IL-1R1）抑制是治疗慢性阻塞性肺疾病（COPD）患者的一种潜在策略。MEDI8968 是一种完全人源化单克隆抗体，能选择性地与 IL-1R1 结合，抑制 IL-1α 和 IL-1β 的激活。我们研究了 MEDI8968 在有症状、中重度 COPD 的成年患者中的疗效和安全性/耐受性。
这是一项 II 期、随机、双盲、安慰剂对照、多中心、平行组研究。年龄在 45-75 岁之间，在过去一年中因 COPD 急性加重（AECOPD）接受过≥2 次标准维持治疗的患者，按 1:1 随机接受安慰剂或 MEDI8968（600mg 静脉负荷剂量）300mg 皮下注射，每 4 周一次，共 52 周。主要终点是中重度 AECOPD 发生率（随机后 56 周）。次要终点为重度 AECOPD 发生率和圣乔治呼吸问卷-COPD（SGRQ-C）评分（随机后 56 周）。
随机分配至安慰剂（n=164）和 MEDI8968（n=160）组的患者中，分别有 79.3%和 75.0%完成了研究。两组在中重度 AECOPD 发生率方面均无统计学差异[90%置信区间（CI）：0.78（0.63，0.96），安慰剂；0.71（0.57，0.90），MEDI8968]，重度 AECOPD 发生率或 SGRQ-C 评分也无差异。根据基线中性粒细胞计数或循环中性粒细胞计数的三分位值进行亚组事后分析，并未改变研究结果。安慰剂和 MEDI8968 治疗组的治疗出现的不良事件（TEAEs）发生率相似。最常见的 TEAE 是 COPD 恶化。
在这项 II 期研究中，MEDI8968 并未显著改善 AECOPD 发生率、肺功能或生活质量。
ClinicalTrials.gov，NCT01448850，注册日期：2011 年 10 月 6 日。
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