EMPIRE-CF: A phase II randomized placebo-controlled trial of once-daily, oral acebilustat in adult patients with cystic fibrosis - Study design and patient demographics
EMPIRE-CF: A phase II randomized placebo-controlled trial of once-daily, oral acebilustat in adult patients with cystic fibrosis - Study design and patient demographics
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DOI：
10.1016/j.cct.2018.07.014
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发表时间：
2018-09-01
影响因子：
2.2
通讯作者：
Rowe, Steven M.
中科院分区：
文献类型：
--
作者：
Elborn, J. Stuart;Ahuja, Sanjeev;Rowe, Steven M.
炎症导致囊性纤维化（CF）肺中不可修复的损伤。尽管有高标准的护理和新疗法的出现，炎症仍然会导致肺功能的显著丧失和发病率。Acebilustat是一种每日一次的口服分子，通过抑制LTA 4水解酶和调节LTB 4而具有抗炎活性。它有可能减少CF患者的肺功能下降和肺加重，目前正在进行II期多中心、随机、双盲、安慰剂对照试验，平行组研究选择基于囊性纤维化基金会患者登记数据建模的严格纳入标准，以丰富最有可能从慢性抗-HCV治疗中获益的患者的试验。减轻肺功能下降的炎症治疗。招募了200例年龄在18 - 30岁之间，FEV 1预测百分比（pp）≥ 50%，并且在过去一年中加重≥ 1次的患者。将患者以1：1：1随机分配至安慰剂、醋比司他50 mg或100 mg，持续48周，与他们当前的护理标准同时服用，并基于同时使用CP FR调节剂、基线FEVipp（50%至75%和> 75%）和过去一年中的恶化次数（1或> 1）分层。主要终点是FEVipp和安全性结局较基线的绝对变化。次要终点包括肺部急性加重的发生率和至首次肺部急性加重的时间。预计EMPIRE-CF将确定未来acebilustat试验的最佳患者人群、剂量、持续时间和终点，并扩大对CF患者药物疗效的理解。
Inflammation causes irreparable damage in the cystic fibrosis (CF) lung. Despite high standards of care and the advent of new therapies, inflammation continues to cause significant loss of lung function and morbidity.Acebilustat is a once-daily, oral molecule with anti-inflammatory activity through the inhibition of LTA4 hydrolase and modulation of LTB4. It has potential to reduce lung function decline and pulmonary exacerbations in patients with CF and is currently being tested in a Phase II multicenter, randomized, double-blind, placebo controlled, parallel-group study (EMPIRE-CF).Strict inclusion criteria based on modeling of the Cystic Fibrosis Foundation Patient Registry data were selected to enrich the trial with patients most likely to benefit from chronic anti-inflammatory therapy that reduces lung function decline. 200 patients between 18 and 30 years of age, with an FEV1 percent predicted (pp) a >= 50%, and a >= 1 exacerbation in the past year have been enrolled. Patients are randomized 1:1:1 to placebo, acebilustat 50 mg or 100 mg for 48 weeks, taken concomitantly with their current standard of care, and stratified based on concomitant CP FR modulator use, baseline FEVipp (50% to 75% and > 75%), and number of exacerbations in the past year (1 or > 1). The primary endpoints are absolute change from baseline in FEVipp and safety outcomes. Secondary endpoints include rate of pulmonary exacerbations and time to first pulmonary exacerbation. Biomarkers of inflammation will also be assessed.EMPIRE-CF is expected to identify the optimal patient population, dose, duration and endpoints for future acebilustat trials, and widen understanding of the drug's efficacy in patients with CF.