关于H4-受体拮抗剂（JNJ-3575 8979）在对未控制成人哮喘患者的疗效：2a期，随机，双盲，安慰剂对照，多中心，
2018/05/08
关于H4-受体拮抗剂（JNJ-3575 8979）在对未控制成人哮喘患者的疗效：2a期，随机，双盲，安慰
剂对照，多中心，平行对照组研究
剂对照，多中心，平行对照组研究
摘要
背景：H4受体拮抗剂在前期临床哮喘模型中的作用支持关于H4受体拮抗剂对人类哮喘治疗中的研究。JNJ-3575 8979是一种高效、高选择性的口服H4受体拮抗剂。
目的：评估H4受体拮抗剂JNJ-39758979在成人哮喘患者中的安全性和有效性。
方法：在这项2a期双盲多中心安慰剂对照研究中，115名符合条件的患者被随机分配到JNJ-39758979 300 mg 每日一次或安慰剂组，试验时长12周。主要疗效指标为第12周测定不吸入支气管扩张剂下的FEV1较基线的变化。次要疗效指标为患者自我评估症状（PRO）变化（哮喘日记日记数据[日间峰流速，沙丁胺醇/沙丁胺醇的使用次数，夜间憋醒和哮喘症状评分]）。
结果：这项研究没有达到主要终点。然而试验结束时，在呼出气一氧化氮、痰嗜酸性粒细胞或血嗜酸性粒细胞升高的亚组中，JNJ-3575 8979较安慰剂能显著改善不吸入支气管舒张剂下的FEV1值，同样的，在嗜酸性粒细胞升高的亚组中，JNJ-3575 8979较安慰剂也能显著改善PRO。安全性，如不良事件率， JNJ-3575 8979与安慰剂之间没有差异。试验中无严重不良反应发生。没有观察到临床相关的实验室检测值的变化。
结论：研究结果提示H4R拮抗剂对嗜酸性粒细胞哮喘患者的肺功能和哮喘控制有潜在的益处，并可进一步证实哮喘的发病机制。
(中日友好医院呼吸与危重症医学科 张科文 摘译 林江涛 审校)
(Clin Exp Allergy. 2018 Apr 23. doi: 10.1111/cea.13154.)
(Clin Exp Allergy. 2018 Apr 23. doi: 10.1111/cea.13154.)
Phase 2a, randomized, double-blind, placebo-controlled, multicenter,parallel-group study of an H4 R-antagonist (JNJ-39758979) in adults with uncontrolled asthma.
Kollmeier AP, Greenspan A, Xu XL
Abstract
BACKGROUND:The effects of H4 R antagonists in preclinical asthma models support the study of antagonists of the H4 R in the treatment of asthma in humans. JNJ-39758979 is a potent and highly-selective oral H4 R antagonist.
OBJECTIVE:We sought to evaluate the safety and efficacy of the H4 R-antagonist JNJ-39758979 in adult patients with uncontrolled asthma.
METHODS:One hundred and fifteen eligible patients were randomly assigned to JNJ-39758979 300 mg or placebo once daily for 12 weeks in this phase 2a, double-blind, multicenter, placebo-controlled study. Primary efficacy was assessed via week-12 change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1 ). Secondary efficacy assessments included patient-reported outcome (PRO) asthma assessments (Asthma Daily Diary data [AM and PM peak expiratory flow rate, number of puffs of albuterol/salbutamol, presence of nocturnal awakenings and asthma symptom score]).
RESULTS:The study did not meet the primary end-point. However, nominally significant improvements in pre-bronchodilator FEV1 were observed with JNJ-39758979 versus placebo at week 12 in pre-specified subgroups with elevated exhaled nitric oxide, sputum eosinophils or blood eosinophils at baseline. Nominally significant improvements across PRO assessments were consistently observed in the overall population, as well as in eosinophilic subgroups. Safety, such as adverse event rates, was comparable between JNJ-39758979 and placebo. No serious adverse events were reported. No clinically relevant changes in laboratory values were observed.
CONCLUSIONS:The findings suggest potential benefit of H4 R antagonists on lung function and asthma control in eosinophilic asthma patients and warrant further evaluation of this mechanism in asthma with eosinophilic inflammation.
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