全人源单克隆抗体安巴韦单抗-罗米司韦单抗对COVID-19患者的安全性与疗效:一项Ⅱ期临床试验  

Safety and efficacy of the fully humanized monoclonal antibodies Amubarvimab-Romlusevimab in COVID-19 patients:A phaseⅡclinical trial

作　　者：邓西龙 徐兴祥 袁静[3] 张政 杨欣平 黎毅敏[6] 张峣 李春明 刘洋 曹轲 张福杰 钟南山 Deng Xilong;Xu Xingxiang;Yuan Jing;Zhang Zheng;Yang Xinping;Li Yimin;Zhang Yao;Li Chunming;Liu Yang;Cao Ke;Zhang Fujie;Zhong Nanshan(Department of Critical Care Medicine,Guangzhou Eighth People′s Hospital,Guangzhou Medical University,Guangzhou 510180,China;Department of Respiratory and Critical Care Medicine,Northern Jiangsu People′s Hospital,Yangzhou 225001,China;Second Department of Infectious Diseases,the Third People′s Hospital of Shenzhen,Shenzhen,518112,China;Shenzhen Institute of Liver Disease,the Third People′s Hospital of Shenzhen,Shenzhen,518112,China;Second Department of Infectious Diseases,Yunnan Provincial Infectious Disease Hospital,Kunming 650399,China;The Respiratory Medicine,the First Affiliated Hospital of Guangzhou Medical University,Guangzhou 510120,China;Brii Biosciences(Beijing)Co.Limited,Beijing 100096,China;Department of Infectious Disease,Beijing Ditan Hospital,Capital Medical University,Beijing 100102,China)

机构地区：[1]广州医科大学附属市八医院重症医学科,广州510180 [2]苏北人民医院呼吸与危重症医学科,扬州225001 [3]深圳市第三人民医院感染二科,深圳518112 [4]深圳市第三人民医院深圳市肝病研究所,深圳518112 [5]云南省传染病医院感染二科,昆明650399 [6]广州医科大学附属第一医院呼吸内科,广州510120 [7]腾盛博药医药技术(北京)有限公司,北京100096 [8]首都医科大学附属北京地坛医院感染科,北京100102

出　　处：《国际呼吸杂志》2023年第7期766-774,共9页International Journal of Respiration

基　　金：国家重点研发计划(2020YFC0861200、2021YFC0864500);腾盛华创医药技术(北京)有限公司新冠中和抗体BRⅡ-196及BRⅡ-198临床开发项目(BRⅡ-196-198-004)。

摘　　要：目的评估单次静脉输注安巴韦单抗和罗米司韦单抗组合在两个剂量水平下给药对我国新型冠状病毒感染(COVID-19)患者的安全性和有效性。方法本研究采用单臂、开放性设计(A组)和单盲、随机、安慰剂对照、平行组设计(B组)。A组纳入了患有重症COVID-19的成人受试者(n=8),全部接受安巴韦单抗和罗米司韦单抗1000 mg/1000 mg单次给药。B组纳入了非重症COVID-19或无症状感染的成人受试者(n=43),以1∶1的比例随机接受抗体联合方案500 mg/500 mg单次静脉输注(抗体组,n=21)或生理盐水(安慰剂组,n=22)给药,其中抗体组2例、安慰剂组1例于给药前退出研究。主要研究终点为安全性评估,包括不良事件及严重不良事件发生率(A组和B组),和第8天鼻咽拭子中严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)RNA水平较基线水平的时间加权变化(B组)。次要终点包括病毒RNA阴转率、COVID-19相关症状的评估和临床转归。结果共有48例受试者进入研究入组并接受研究给药。A组5/8例受试者发生了12例次不良事件。B组抗体组和安慰组的受试者中不良事件发生率分别为73.7%(14/19)和71.4%(15/21)。不良事件中96.6%为1级或2级,与研究药物相关的不良事件2例次(均为1~2级)。未报告输液反应、与研究药物相关的严重不良事件、死亡或导致研究终止的不良事件。在给药后29 d的疗效评估期内,A组受试者中无因COVID-19进展使用机械通气或发生死亡。B组中抗体组和安慰剂组第8天的加权SARS-CoV-2 RNA水平较基线降低的平均值均为1.2 log10拷贝/检测(t=0.13,P=0.894)。B组中抗体组和安慰剂组达到症状充分改善的中位时间分别为8.0 d和10.0 d;抗体组有0例、安慰剂组有1例受试者进展为重症。结论安巴韦单抗和罗米司韦单抗在我国COVID-19患者的Ⅱ期临床研究中表现出良好的安全性、耐受性及临床获益趋势。Objective The aim of the study is to evaluate the safety and efficacy of two different dosage of Amubarvimab and Romlusevimab combination in patients with COVID-19 in China.Methods This study used a single arm,open-label design in Group A,and a single-blinded,randomized,placebo-controlled,parallel design in Group B.Adult subjects with severe COVID-19 were enrolled in Group A(n=8),all of whom received a single dose of 1000 mg Amubarvimab and 1000 mg Romlusevimab.Adult subjects with non-severe COVID-19 or asymptomatic infection were enrolled in Group B(n=43),who were randomized 1∶1 to receive a combined regimen(500 mg Amubarvimab and 500mg Romlusevimab,single intravenous infusion,antibody group,n=21)or placebo administration(placebo group,n=22).Two cases in the antibody group and 1 case in the placebo group withdrew from the study before administration.Primary end point of the study was safety assessment,including the incidence of adverse events(AEs)and serious adverse events(SAEs)(Group A and B),and time weighted changes in severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)RNA levels in nasopharyngeal swabs from baseline on Day 8(Group B).Secondary endpoints included negative conversion rate of viral RNA,COVID-19 related symptom evaluation and clinical outcomes.Results A total of 48 subjects were enrolled and received study medication.In Group A,12 AEs occurred in 5/8 subjects.In Group B,the incidence of AEs among subjects receiving a combined antibody regimen and a placebo(saline)was 73.7%(14/19)and 71.4%(15/21),respectively.Among all AEs,96.6%was considered as grade 1 or 2,and two drug-related AEs were reported by the investigators as grade 1-2.No infusion reactions,drug-related SAEs,death,or study AEs leading to termination were reported.During the efficacy evaluation period 29 days after administration,no patients in Group A received mechanical ventilation or died due to COVID-19 progression.In Group B,time-weighted changes of SARS-CoV-2 RNA at day 8 declined 1.2 log10copies/test from baseline

关 键 词：新型冠状病毒感染 单克隆中和抗体 安全性 

分 类 号：R969.3[医药卫生—药理学]