"Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial"

作者全名："Zhang, Yuan; Yan, Bing; Shen, Shen; Song, Xicheng; Jiang, Yan; Shi, Li; Zhao, Changqing; Yang, Yi; Jiang, Luyun; Li, Jiping; Ye, Jing; Liu, Jinfeng; Wan, Lijia; Yang, Yucheng; Chen, Jianjun; Liu, Feng; Su, Lizhong; Xu, Yu; Tan, Guolin; Yu, Shaoqing; Zhang, Yu; Wang, Lin; Liu, Shengyang; Yan, Hongyue; Liu, Wei; Chen, Bo; Wang, Chengshuo; Zhang, Luo"

作者地址："[Zhang, Yuan; Zhang, Luo] Capital Med Univ, Beijing TongRen Hosp, Dept Allergy, Beijing 100005, Peoples R China; [Yan, Bing; Shen, Shen; Liu, Shengyang; Wang, Chengshuo; Zhang, Luo] Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing 100730, Peoples R China; [Yan, Bing; Shen, Shen; Wang, Chengshuo; Zhang, Luo] Capital Med Univ, Beijing Inst Otolaryngol, Beijing Lab Allerg Dis,Minist Educ, Beijing Key Lab Nasal Dis,Key Lab Otolaryngol Hea, Beijing 100005, Peoples R China; [Yan, Bing; Shen, Shen; Wang, Chengshuo; Zhang, Luo] Chinese Acad Med Sci, Res Unit Diag & Treatment Chron Nasal Dis, Beijing 100005, Peoples R China; [Song, Xicheng; Zhang, Yu] Qingdao Univ, Yantai Yuhuangding Hosp, Dept Otorhinolaryngol Head & Neck Surg, Yantai 264000, Shandong, Peoples R China; [Song, Xicheng; Liu, Feng; Zhang, Yu] Shandong Prov Clin Res Ctr Otorhinolaryngol Dis, Yantai 264000, Shandong, Peoples R China; [Jiang, Yan; Wang, Lin] Qingdao Univ, Dept Otorhinolaryngol Head & Neck Surg, Affiliated Hosp, Qingdao 266003, Shandong, Peoples R China; [Shi, Li] Shandong Univ, Shandong Prov ENT Hosp, Dept Otorhinolaryngol Head & Neck Surg, Jinan 250000, Shandong, Peoples R China; [Zhao, Changqing] Shanxi Med Univ, Dept Otorhinolaryngol, Hosp 2, Taiyuan 030000, Shanxi, Peoples R China; [Yang, Yi] Beijing Hosp, Dept Otorhinolaryngol, Beijing 100730, Peoples R China; [Jiang, Luyun] Chengdu Univ Tradit Chinese Med, Dept Otorhinolaryngol, Chengdu 610075, Sichuan, Peoples R China; [Li, Jiping] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Otorhinolaryngol, Shanghai, Peoples R China; [Ye, Jing] Nanchang Univ, Dept Otorhinolaryngol Head & Neck Surg, Affiliated Hosp 1, Nanchang 330000, Jiangxi, Peoples R China; [Liu, Jinfeng] Capital Med Univ, Beijing Chao Yang Hosp, Dept Otorhinolaryngol Head & Neck Surg, Beijing 100020, Peoples R China; [Wan, Lijia] Yangtze Univ, Dept Otorhinolaryngol, Jingzhou Hosp, Jingzhou 434020, Hubei, Peoples R China; [Yang, Yucheng] Chongqing Med Univ, Dept Otorhinolaryngol, Affiliated Hosp 1, Chongqing 400042, Peoples R China; [Chen, Jianjun] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Otorhinolaryngol, Wuhan 430022, Hubei, Peoples R China; [Liu, Feng] Sichuan Univ, West China Hosp, Dept Otolaryngol Head & Neck Surg, Chengdu 610066, Sichuan, Peoples R China; [Su, Lizhong] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Dept Otorhinolaryngol, Peoples Hosp, Hangzhou 310014, Zhejiang, Peoples R China; [Xu, Yu] Wuhan Univ, Dept Otorhinolaryngol Head & Neck Surg, Renmin Hosp, Wuhan 430060, Hubei, Peoples R China; [Tan, Guolin] Cent South Univ, Dept Otorhinolaryngol Head & Neck Surg, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China; [Yu, Shaoqing] Tongji Univ, Sch Med, Tongji Hosp, Dept Otolaryngol Head & Neck Surg, Shanghai 200065, Peoples R China; [Yu, Shaoqing] Tongji Univ, Sch Med, Tongji Hosp, Dept Allergy, Shanghai 200065, Peoples R China; [Yan, Hongyue; Liu, Wei; Chen, Bo] Keymed Biosci Chengdu Ltd, Clin Dept, Chengdu 610219, Sichuan, Peoples R China"

通信作者："Zhang, L (通讯作者)，Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, 1 Dongjiaominxiang, Beijing 100730, Peoples R China.; Wang, CS (通讯作者)，Beijing Inst Otolaryngol, 17 HouGouHuTong, Beijing 100005, Peoples R China."

来源：ECLINICALMEDICINE

ESI学科分类：　

WOS号：WOS:001041582500001

JCR分区：Q1

影响因子：9.6

年份：2023

卷号：61

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Chronic rhinosinusitis with nasal polyps; RCT; Placebo-controlled; Double-blind; Anti-interleukin-4 receptor alpha monoclonal antibody

摘要："Background Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP. Methods A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398. symbolscript Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study.Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were -2.1 (95% CI -2.9, -1.4; p < 0.0001) and -0.9 (95% CI -1.4, -0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] -7.6, [-9.4, -5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] -37%, [-47%, -28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (-2.6 [95% CI -3.5,-1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (-19.1 [95% CI -29.8,-8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related.Interpretation These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP."

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