The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma
The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma
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DOI：
10.1016/j.jaci.2012.12.1561
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发表时间：
2013-03-01
影响因子：
14.2
通讯作者：
Renner, Wolfgang A.
中科院分区：
文献类型：
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作者：
Beeh, Kai-Michael;Kanniess, Frank;Renner, Wolfgang A.
背景：过敏原特异性T（H）2反应参与过敏性哮喘的发生。它们的增加可能是由于早期暴露于环境病原体的减少，这诱导了T（H）1反应，从而抑制了过敏性T（H）2反应。QbG10目的：设计一种新型的Toll样受体9激动剂（含CpG基序G10的噬菌体Q β衍生病毒样颗粒），包装在病毒样颗粒中，用于刺激免疫系统产生T（H）1介导的保护性应答。我们检查了临床疗效，安全性，QbG 10在轻度至中度持续性过敏性哮喘患者中的耐受性和患者报告的客观临床结果参数。在这项概念验证平行组、双盲、随机试验中，63名哮喘患者转换为标准化吸入性类固醇，并接受7次QbG 10或安慰剂注射治疗。控制类固醇戒断，对患者的影响-报告（白天和夜间哮喘症状、沙丁胺醇使用情况和7项哮喘控制问卷评分）和客观临床结局指标在12周内评估FEV 1、呼出气一氧化氮分数和血嗜酸性粒细胞（ClinicalTrials.gov编号，NCT 00890734）。在QbG 10治疗患者（n=33）中，尽管停用类固醇，但所有患者报告的参数在第0周至第12周之间总体改善，与安慰剂组观察到的恶化相比（n=30，P
Background: Allergen-specific T(H)2 responses contribute to the development of allergic asthma. Their increase may be due to a reduced early exposure to environmental pathogens, which induces a T(H)1 response, and thereby suppresses the allergic T(H)2 response. QbG10 (bacteriophage Qbeta-derived virus-like particle with CpG-motif G10 inside), a novel Toll-like receptor 9 agonist packaged into virus-like particles, was designed to stimulate the immune system toward a T(H)1-mediated protective response.Objective: We examined clinical efficacy, safety, and tolerability of QbG10 with patient-reported and objective clinical outcome parameters in patients with mild-to-moderate persistent allergic asthma.Methods: In this proof-of-concept parallel-group, double-blind, randomized trial, 63 asthmatic patients followed conversion to a standardized inhaled steroid and were treated with 7 injections of either QbG10 or placebo. Incorporating a controlled steroid withdrawal, the effects on patient-reported (day- and nighttime asthma symptoms, salbutamol usage, and 7-item-Asthma Control Questionnaire scores) and objective clinical outcome measures (FEV1, fraction of exhaled nitric oxide, and blood eosinophils) were assessed over 12 weeks (ClinicalTrials.gov number, NCT00890734).Results: All patient-reported parameters improved overall between week 0 and 12 in QbG10-treated patients (n=33) despite steroid withdrawal, compared with deteriorations observed under placebo (n=30, P