Castro Mario, Kerwin Edward, Miller David, Pedinoff Andrew, Sher Lawrence, Cardenas Pamela, Knorr Barbara, Lawrence David, Ossa Diego, Wang Wei, Maspero Jorge F
Division of Pulmonary, Critical Care Medicine, University of Kansas School of Medicine, Kansas City, KS, USA.
Clinical Research Institute of Southern Oregon, Medford, OR, USA.
EClinicalMedicine. 2021 Apr 25;35:100847. doi: 10.1016/j.eclinm.2021.100847. eCollection 2021 May.
These studies assessed the efficacy and safety of fevipiprant, an oral antagonist of the prostaglandin D (PGD) receptor (DP), compared with placebo when added to standard-of-care (SoC) asthma therapy in patients with uncontrolled asthma.
ZEAL-1 (NCT03215758) and ZEAL-2 (NCT03226392) are two replicate, phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies in which fevipiprant 150 mg once daily (o.d.) or placebo was added to SoC asthma therapy in patients aged ≥12 years with uncontrolled asthma. Primary endpoint: change from baseline in pre-dose forced expiratory volume in 1 s (FEV) after 12 weeks' treatment. Key secondary endpoints: daytime asthma symptom score, short-acting β-agonist (SABA) use and Asthma Quality-of-Life Questionnaire (AQLQ+12) score after 12-weeks treatment.
662 patients in ZEAL-1 and 685 patients in ZEAL-2 completed the treatment period. In ZEAL-1, the least squares (LS) mean change from baseline in pre-dose FEV was 112 mL in fevipiprant vs 71 mL in placebo group (difference [∆]:41 mL; 95% CI: -6, 88; adjusted p-value 0·088). In ZEAL-2, the LS mean change in pre-dose FEV was 126 mL and 157 mL in the fevipiprant and placebo groups, respectively (∆:-31 mL; 95% CI: -80, 18; adjusted p-value 0·214). For both studies, there were no statistically significant differences in the key secondary objectives between the treatment groups.
The ZEAL studies did not demonstrate significant improvement in lung function or other clinical outcomes. These results suggest that DP receptor inhibition with fevipiprant is not effective in the studied patient population.
这些研究评估了在标准治疗（SoC）哮喘治疗基础上添加口服前列腺素D（PGD）受体（DP）拮抗剂非维吡兰特与安慰剂相比，对未控制哮喘患者的疗效和安全性。
ZEAL-1（NCT03215758）和ZEAL-2（NCT03226392）是两项重复的3期多中心随机双盲安慰剂对照平行组研究，将150毫克非维吡兰特每日一次（o.d.）或安慰剂添加到年龄≥12岁的未控制哮喘患者的SoC哮喘治疗中。主要终点：治疗12周后，给药前1秒用力呼气量（FEV）相对于基线的变化。关键次要终点：治疗12周后的日间哮喘症状评分、短效β受体激动剂（SABA）使用情况和哮喘生活质量问卷（AQLQ+12）评分。
ZEAL-1中的662名患者和ZEAL-2中的685名患者完成了治疗期。在ZEAL-1中，非维吡兰特组给药前FEV相对于基线的最小二乘（LS）均值变化为112毫升，而安慰剂组为71毫升（差值[∆]：41毫升；95%置信区间：-6，88；校正p值0.088）。在ZEAL-2中，非维吡兰特组和安慰剂组给药前FEV的LS均值变化分别为净变化126毫升和157毫升（∆：-31毫升；95%置信区间：-80，18；校正p值0.214）。对于两项研究，治疗组之间的关键次要目标均无统计学显著差异。
ZEAL研究未显示肺功能或其他临床结局有显著改善。这些结果表明，在研究的患者群体中，非维吡兰特抑制DP受体无效。
