广州本瑞利珠单抗注射液III期临床试验-一项在接受中剂量 ICS-LABA 治疗后控制不佳的嗜酸性粒细胞哮喘患者中研究与常规递增至高剂量 ICS-LABA 治疗相比加用本瑞利珠单抗 30 mg SC 的疗效和安全性的随机临床试验

登记号	CTR20251810	试验状态	进行中
申请人联系人	徐金瑞	首次公示信息日期	2025-05-08
申请人名称	AstraZeneca AB/ 阿斯利康投资（中国）有限公司/ Catalent Indiana, LLC

登记号	CTR20251810
相关登记号	暂无
药物名称	本瑞利珠单抗注射液
药物类型	生物制品
临床申请受理号	企业选择不公示
适应症	用于12岁及以上，经中剂量吸入性糖皮质激素（ICS）联合LABA治疗后仍控制不佳的，伴有血嗜酸性粒细胞升高（≥150/ul）的哮喘患者的附加维持治疗
试验专业题目	BRISOTE：一项在接受中剂量吸入性皮质类固醇联合长效 β2-激动剂治疗后控制不佳的嗜酸性粒细胞哮喘患者中评估皮下注射本瑞利珠单抗 30 mg 的疗效和安全性的多中心、随机、双盲、平行组、阳性对照、IIIb 期研究
试验通俗题目	一项在接受中剂量 ICS-LABA 治疗后控制不佳的嗜酸性粒细胞哮喘患者中研究与常规递增至高剂量 ICS-LABA 治疗相比加用本瑞利珠单抗 30 mg SC 的疗效和安全性的随机临床试验
试验方案编号	D3250C00101	方案最新版本号	2.0
版本日期:	2024-09-27	方案是否为联合用药	是

申请人名称	[["AstraZeneca AB"],["阿斯利康投资（中国）有限公司"],["Catalent Indiana, LLC"]]
联系人姓名	徐金瑞	联系人座机	010-58326447	联系人手机号
联系人Email	Clinical-Trial-Disclosure-Mailbox@astrazeneca.com	联系人邮政地址	上海市-上海市-浦东亮景路199号	联系人邮编	201203

主要目的：在接受中剂量ICS-LABA治疗后控制不佳的嗜酸性粒细胞哮喘患者中通过比较加用本瑞利珠单抗与高剂量ICS-LABA递增治疗评估本瑞利珠单抗对哮喘加重率的影响 次要目的：在接受中剂量ICS-LABA治疗后控制不佳的嗜酸性粒细胞哮喘患者中通过比较加用本瑞利珠单抗与高剂量ICS-LABA递增治疗，评估本瑞利珠单抗对患者报告疾病特定生活质量的影响、对肺功能的影响、对患者报告的哮喘控制、生活质量和生产力损失的影响、对至首次哮喘加重的时间的影响、对因哮喘而进行急诊室/紧急护理访视和住院的影响、对4分量临床缓解复合指标的影响 安全性目的：在接受中剂量ICS-LABA治疗后控制不佳的嗜酸性粒细胞哮喘患者中通过比较加用本瑞利珠单抗与高剂量ICS-LABA递增治疗描述本瑞利珠单抗的安全性和耐受性 探索性目的：在接受中剂量ICS-LABA治疗后控制不佳的嗜酸性粒细胞哮喘患者中通过比较加用本瑞利珠单抗与高剂量ICS-LABA递增治疗,评估本瑞利珠单抗对血生物标志物的影响、描述本瑞利珠单抗对3分量和附加的4分量临床缓解复合指标的影响

试验分类	安全性和有效性	试验分期	III期	设计类型	平行分组
随机化	随机化	盲法	双盲	试验范围	国际多中心试验

年龄	12岁(最小年龄)至 75岁(最大年龄)
性别	男+女
健康受试者	无
入选标准	[["获得书面知情同意书"],["受试者年龄必须为 12 - 75 岁（包括 12 岁和 75 岁）"],["在访视 1 前至少 12 个月有医生诊断的哮喘病史，需要使用至少中剂量的 ICS（丙酸氟替卡松干粉制剂当量每日总剂量 > 250 μg）和一种 LABA 进行治疗"],["在访视 1 前接受过有据可查的中剂量 ICS 和 LABA 治疗至少 3 个月，联合或不联合其他哮喘控制药物（不包括口服皮质类固醇）"],["体重 ≥ 35 kg"],["BD 前 FEV1 预测值 ≤ 90%（访视 2）"],["在知情同意日期之前的 12 个月内，记录有至少 2 次哮喘加重"],["访视 1 时 ACQ-6 评分 ≥ 1.5;在导入期（从访视 2 至访视 3）以及访视 3 时至少一次 ACQ-6 评分 ≥1.5"],["通过满足方案中定义的标准，证明肺功能变异性过大而记录的哮喘证据"],["访视 1 时当地实验室评估的外周血嗜酸性粒细胞计数 ≥ 150 个细胞/μL"],["根据哮喘每日日记，在导入期（从访视 2 至访视 3）期间，对常规哮喘控制药物 ICS-LABA 的依从性至少为 70%。"]]
排除标准	[["研究者判断的除哮喘以外的重要肺部疾病，或曾被诊断患有哮喘以外与外周嗜酸性粒细胞计数升高相关的肺部或全身性疾病。"],["在获得知情同意的日期之前 30 天内或在筛选/导入期期间，需要使用 SCS 治疗的哮喘加重或需要使用抗生素或抗病毒药物治疗的急性上/下呼吸道感染"],["研究者认为影响研究的任何不稳定的疾病"],["需要全身治疗的具有临床意义的慢性或持续性活动性感染（由研究者酌情决定）"],["同期参与另一项采用一种 IP 进行的临床研究或一项批准后安全性研究"],["在获得知情同意的日期之前 12 个月内有酗酒或药物滥用史"],["当前吸烟者或既往吸烟者，吸烟史 ≥ 10 包-年。既往吸烟者必须在访视 1 之前戒烟至少 6 个月才有资格"]]

试验药	[["中文通用名:本瑞利珠单抗注射液 英文通用名:BenralizumabInjection 商品名称:凡舒卓","剂型:注射剂 规格:30mg/ml 用法用量:皮下注射，每次1mL 用药时程:前3剂每4周一次，随后每8周给药一次"]] 序号 名称 用法
对照药	[["中文通用名:安慰剂 英文通用名:NA 商品名称:NA","剂型:注射剂 规格:30mg/ml(含20mML-组氨酸/L-组氨酸盐酸盐一水合物、0.25M海藻糖二水合物和0.006%w/v聚山梨酯20) 用法用量:皮下注射，每次1mL 用药时程:前3剂每4周一次，随后每8周给药一次"]] 序号 名称 用法

主要终点指标及评价时间

[["哮喘年加重率","48 周治疗期间","有效性指标"]] 序号 指标 评价时间 终点指标选择

次要终点指标及评价时间

[["EOT（第 48 周）的 SGRQ 总评分较基线的变化","48 周治疗期间","有效性指标"],["EOT（第 48 周）和治疗期间 BD 前 FEV1 较基线的变化","48 周治疗期间","有效性指标"],["EOT（第 48 周）和治疗期间 ACQ-6 较基线的变化","48 周治疗期间","有效性指标"],["从基线至 EOT（第 48 周）达到临床有意义的 ACQ-6 改善（定义为较基线下降 ≥ 0.5 分）的受试者比例","48 周治疗期间","有效性指标"],["治疗期间达到哮喘控制（定义为 ACQ-6 < 1.5）的受试者比例","48 周治疗期间","有效性指标"],["治疗期间 SGRQ 从基线至第 4、8、16 和 32 周的变化","48 周治疗期间","有效性指标"],["从基线至 EOT 达到临床有意义的 SGRQ 总评分改善（定义为较基线下降 ≥ 4 个单位）的受试者比例","48 周治疗期间","有效性指标"],["EOT（第 48 周）和治疗期间急救药物使用较基线的变化","48 周治疗期间","有效性指标"],["EOT（第 48 周）和治疗期间的 PGI-S 和 PGI-S 较基线的变化","48 周治疗期间","有效性指标"],["生产力损失从基线至 EOT（第 48 周）的变化","48 周治疗期间","有效性指标"],["至首次哮喘加重的时间","48 周治疗期间","有效性指标"],["在 48 周的治疗期间与急诊室/紧急护理访视或住院治疗相关的加重的 AAER","48 周治疗期间","有效性指标"],["第24周和EOT时符合4分量临床缓解复合指标中每个分量的受试者人数和比例n在第24周和EOT时符合复合缓解终点的0、1、2、3和所有4个分量的受试者人数和比例","48 周治疗期间","有效性指标"],["AE、SAE、DAE；实验室参数和生命体征","48 周治疗期间","安全性指标"],["血嗜酸性粒细胞计数和 FeNO 较基线的变化：随时间的实测值和较基线的变化","48 周治疗期间","有效性指标"],["在第24周和EOT时符合3分量临床缓解复合指标的受试者人数和比例n在第24周和EOT时符合复合缓解终点的0、1、2 和所有3个分量的受试者人数和比例","48 周治疗期间","有效性指标"],["第24周和EOT时符合4分量临床缓解复合指标的受试者人数和比例n在第24周和EOT时符合复合缓解终点的0、1、2、3 和所有4个分量的受试者人数和比例","48 周治疗期间","有效性指标"]] 序号 指标 评价时间 终点指标选择

1	姓名	陈如冲；钟南山	学位	医学博士	职称	主任医师
	电话	13710723826	Email	Chen_rch@163.com	邮政地址	广东省-广州市-荔湾区桥中中路28号
	邮编	510120	单位名称	广州医科大学附属第一医院

[["广州医科大学附属第一医院","陈如冲；钟南山","中国","广东省","广州市"],["温州医科大学附属第二医院/育英儿童医院","戴元荣","中国","浙江省","温州市"],["浙江省人民医院","孙益兰","中国","浙江省","杭州市"],["秦皇岛市第一医院","徐淑凤","中国","河北省","秦皇岛市"],["宁夏医科大学总医院","侯嘉","中国","宁夏回族自治区","银川市"],["上海市第一人民医院","张旻","中国","上海市","上海市"],["徐州医科大学附属医院","陈碧","中国","江苏省","徐州市"],["惠州市第三人民医院","吴峰","中国","广东省","惠州市"],["长沙市中心医院","杨红忠","中国","湖南省","长沙市"],["重庆医科大学附属第一医院","郭述良","中国","重庆市","重庆市"],["北京清华长庚医院","牟向东","中国","北京市","北京市"],["广州市第一人民医院","魏树全","中国","广东省","广州市"],["上海市肺科医院","程克斌","中国","上海市","上海市"],["北京大学人民医院","高占成","中国","北京市","北京市"],["河南中医药大学第一附属医院","王明航","中国","河南省","郑州市"],["福建省福州结核病防治院/福建省福州肺科医院","王新航","中国","福建省","福州市"],["合肥市第一人民医院","钟明媚","中国","安徽省","合肥市"],["山东省立医院","刘毅","中国","山东省","济南市"],["华中科技大学同济医学院附属同济医院","谢敏","中国","湖北省","武汉市"],["浙江大学医学院附属第一医院","周建娅","中国","浙江省","杭州市"],["Recherche Clinique Sigma Inc.","Guy Chouinard","加拿大","Quebec","Québec"],["St. James's University Hospital","Rashad Salman","英国","Leeds","Leeds"],["Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital","Thomas Brown","英国","Hampshire","Portsmouth"],["Dynamic Drug Advancement Limited","George Philteos","加拿大","Ontario","Ajax"],["Hospital Universitari Germans Trias i Pujol","Carlos Martinez Rivera","西班牙","Barcelona","Barcelona"],["Kantonsspital St. Gallen","Frank Rassouli","瑞士","St. Gallen","St. Gallen"],["Policlinico Universitario Monserrato","Stefano Del Giacco","意大利","Sardegna","Cagliari"],["Northwell Health - Centers for Advanced Medicine","Mina Makaryus","美国","New York","New Hyde Park"],["Hospital Universitario Virgen de las Nieves","Concepcion Morales Garcia","西班牙","Granada","Granada"],["Centre Hospitalier Universitaire Vaudois","Christophe von Garnier","瑞士","Lausanne","Lausanne"],["Medical Arts Health Research Group - Kamloops","Keith Hutchison","加拿大","British Columbia","Kamloops"],["Prime Healthcare - Inglewood","Patel Paryus","美国","California","Inglewood"],["Allergic Disease & Asthma Center, P.A. (ADAC) - Butler Road Office","Neil Kao","美国","South Carolina","Greenville"],["Urban Health Plan","Samuel DeLeon","美国","New York","Bronx"],["Florida Premier Research Institute - Clay Street","Alfonso Gonzalez-Rodriguez","美国","Florida","Winter Park"],["Hospital Universitari Son Espases","Francisco de Borja Garcia-Cosio Piqueras","西班牙","Baleares","Palma de Mallorca"],["Hospital Universitario Ramón y Cajal","Silvia Sanchez Cuellar","西班牙","Madrid","Madrid"],["Hospital Universitario de La Ribera","Inmaculada Lluch Tortajada","西班牙","Valencia","Alzira"],["Hospital San Pedro de Alcántara","Manuel Agustin Sojo Gonzalez","西班牙","Cáceres","Cáceres"],["South Texas Allergy & Asthma Medical Professionals (STAAMP)","Erika Gonzalez","美国","Texas","San Antonio"],["National Jewish Health","Rohit Katial","美国","Colorado","Denver"],["Portiuncula University Hospital","Hilary McLoughlin","爱尔兰","Contae na Gaillimhe","Ballinasloe"],["University First Multiprofile Hospital for Active Treatment - Sofia","Dinko Valev","保加利亚","Sofia","Sofia"],["Institut Universitaire de Cardiologie et de Pneumologie de Québec","Andreanne Cote","加拿大","Québec","Québec"],["Hospital Universitario de Burgos","Maria Victoria Garcia Gallardo Sanz","西班牙","Burgos","Burgos"],["CHU Hopitaux de Bordeaux - Hopital Haut-Leveque","Patrick Berger","法国","Nouvelle-Aquitaine","Pessac"],["Hospital San Eloy","Jesus Camino Buey","西班牙","Bizkaia","Barakaldo"],["Hospital de Merida","Antonio Manuel Perez Fernandez","西班牙","Extremadura","Merida"],["Hopital Larrey","Laurent Guilleminault","法国","Haute-Garonne","Toulouse"],["Centre Hospitalier de la Cote Basque","Cecilia Nocent","法国","Basque","Bayonne"],["Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento","Marco Caminati","意大利","Verona","Verona"],["Ospedale Policlinico San Martino","Fulvio Braido","意大利","Genova","Genova"],["Pneumologisches Forschungsinstitut Hohegeest GbR","Wolfgang Zachgo","德国","Schleswig-Holstein","Geesthacht"],["NewportNativeMD, Inc.","Ryan Klein","美国","California","Newport Beach"],["University Hospitals Birmingham NHS Foundation Trust - Heartlands Hospital","Adel Mansur","英国","West Midlands","Birmingham"],["Clinical Research Trials of Florida, Inc.","Sady Alpizar","美国","Florida","Tampa"],["Bradford Teaching Hospitals NHS Foundation Trust - Bradford Royal Infirmary","Dinesh Saralaya","英国","West Yorkshire","Bradford"],["Hospital Universitario 12 de Octubre","Ismael Garcia Moguel","西班牙","Madrid","Madrid"],["Hospital Universitario Vall d'Hebron","Xavier Munoz","西班牙","Catalunya","Barcelona"],["Hospital Universitario de Jerez de la Frontera","Jose Gregorio Soto Campos","西班牙","Cadiz","Jerez"],["Fondazione Policlinico Universitario Agostino Gemelli","Cristiano Caruso","意大利","Roma","Roma"],["Lungenfacharztzentrum Wiesbaden","Peter Fried","德国","Rhine-Main","Wiesbaden"],["Preventsia 2000 - Medical Centre for Outpatient Medical Care OOD","Vanya Dimova Ilieva-Fartunova","保加利亚","Stara Zagora","Stara Zagora"],["Connolly Hospital Blanchardstown","Abirami Subramaniam","爱尔兰","Dublin","Dublin"],["MC Fama Medical EOOD","Blagoy Marinov","保加利亚","Plovdiv","Plovdiv"],["Lynn Health Science Institute East","Charles Lunn","美国","Oklahoma","Oklahoma"],["Research Center for Medical Studies (RCMS)","Bjoern Martens","德国","Berlin","Berlin"],["Hospital Costa del Sol","Alicia Padilla-Galo","西班牙","Malaga","Marbella"],["Hospital Universitario Virgen de la Victoria","Jose Luis Velasco Garrido","西班牙","Málaga","Málaga"],["Hopital de la Croix-Rousse","Gilles Devouassoux","法国","Auvergne-Rhone-Alpes","Lyon"],["AORN - Ospedali dei Colli Ospedale V. Monaldi","Anna Stanziola","意大利","Campania","Napoli"],["University Multiprofile Hospital for Active Treatment “Alexandrovska”","Maria Staevska-Kotasheva","保加利亚","Sofia","Sofia"],["Our Lady of Lourdes Hospital - Drogheda","Tidi Hassan","爱尔兰","Louth","Drogheda"],["Henderson Clinical Trials, LLC","Vikas Sayal","美国","Nevada","Henderson"],["Noble Clinical Research - Elite Clinical Network","Dena Petersen","美国","Arizona","Tucson"],["University of Michigan Health System - A. Alfred Taubman Health Care Center - Pulmonary Clinic","Arjun Mohan","美国","Michigan","Ann Arbor"],["Lancashire Teaching Hospitals NHS Foundation Trust - Chorley and South Ribble Hospital","Kathryn Prior","英国","Lancashire","Chorley"],["Frau Dr. med. Karin Forster","Karin Forster","德国","Berlin","Berlin"],["Metroplex Pulmonary and Sleep Center","Shahrukh Kureishy","美国","Texas","McKinney"],["Hospital Universitario Marqués de Valdecilla","Juan Luis Garcia Rivero","西班牙","Cantabria","Santander"],["Hospital de la Santa Creu i Sant Pau","David Ramos Barbon","西班牙","Catalunya","Barcelona"],["Inspiration Research Limited","Kenneth Chapman","加拿大","Ontario","Toronto"],["Istituto Clinico Humanitas","Stefano Aliberti","意大利","Milan","Rozzano"],["Kantonsspital Aarau AG","Hans-Joachim Kabitz","瑞士","Aargau","Aarau"],["Cork University Hospital","Desmond Murphy","爱尔兰","Cork","Cork"],["Pharmax Research of South Florida, Inc","Lourdes Bosch","美国","Florida","Miami"],["Klinikum der Universitat München","Alexandra Lenoir","德国","Freistaat Bayern","Muenschen"],["The Lung Centre","Celine Bergeron","加拿大","British Columbia","Vancouver"],["North Bristol NHS Trust - Southmead Hospital Bristol","James Dodd","英国","Bristol","Bristol"],["Medipole Lyon - Villeurbanne","Jean-Marc Dot","法国","Rhone","Villeurbanne"],["Hospital Quiron Marbella (Antiguo USP Hospital de Marbella)","Jose-Maria Ignacio-Garcia","西班牙","Marbella","Marbella"],["Centre Hospitalier Intercommunal de Créteil","Amel Boudjemaa","法国","Marne la Vallée","Creteil"],["Azienda Ospedaliero - Universitaria di Modena Policlinico","Bianca Beghe","意大利","Modena","Modena"],["Ospedale di Montebelluna","Francesco Menzella","意大利","Treviso","Montebelluna"],["Azienda Ospedaliero - Universitaria Consorziale Policlinico di Bari","Giovanna Elisiana Carpagnano","意大利","Bari","Bari"],["ASST Papa Giovanni XXIII","Fabiano Di Marco","意大利","Bergamo","Bergamo"],["Prince of Wales Hospital","David Shu-Cheong Hui","中国香港","香港","Sha Tin"],["MECS Cottbus GmbH","Frank Kaessner","德国","Brandenburg Land","Cottbus"],["Rush University Medical Center","Priya Mishra","美国","Illinois","Chicago"],["Pasadena Clinical Trials","Tzu-Jen Tzao","美国","California","Pasadena"],["SRA Trials North","Maria Bermudez","美国","Florida","Florida"],["Pediatric Pulmonary & Asthma Associates of South Jersey, LLC","Mila Leong","美国","NJ","Northfield"],["Nottingham University Hospitals NHS Trust - City Hospital","Sherif Gonem","英国","Nottingham","Nottingham"],["Clinical Research Associates of Central PA","Sandeep Bansal","美国","Illinois","Chicago"],["Hospital Universitario Fundación Alcorcón","Ana Rosado","西班牙","Madrid","Alcorcón"],["University Hospital Lucus Augusti","Luis Alejandro Perez de Llano","西班牙","Galicia","Lugo"],["Dr. Syed Anees Medicine Professional Corporation","Syed Anees","加拿大","Ontario","Windsor"],["ASST degli Spedali Civili di Brescia","Laura Pini","意大利","Brescia","Brescia"],["Akershus Universitetssykehus HF","Gunnar Einvik","挪威","Akershus","Loerenskog"],["Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes)","Christel Saint Raymond","法国","Isère","La Tronche"],["Sun City Clinical Research","Juan Rodriguez","美国","Arizona","Sun City"],["C&A Clinical Trials Safety First","Juan Carmona","美国","Florida","Cape Coral"],["Belfast Health and Social Care Trust - Belfast City Hospital","Liam Heaney","英国","Béal Feirste","Béal Feirste"],["Aapri Clinical Research Institute","John Zwetchkenbaum","美国","Rhode Island","Warwick"],["Velocity Clinical Research Germany GmbH","Konstanze Landerholm","德国","Schleswig-Holstein","Lübeck"],["Queen Mary Hospital","David Chi-Leung Lam","中国香港","香港","Pok Fu Lam"],["University Hospital Basel","Antje Prasse","瑞士","Basel","Basel"],["CHRU Montpellier - Arnaud de Villeneuve","Arnaud Bourdin","法国","Hérault","Montpellier"],["Hopital Foch","Colas Tcherakian","法国","Hauts-de-Seine","Suresnes"],["Policlinico Milano","Mirta Cavallini","意大利","Milano","Milano"],["Policlinico Umberto I","Matteo Bonini","意大利","Rome","Rome"],["Heuer M.D. Research, Inc.","Marvin Heuer","美国","Florida","Orlando"],["Universitá degli Studi","Girolamo Pelaia","意大利","Catanzaro","Catanzaro"],["Flourish Research - Leesburg","Jose Diaz","美国","Florida","Leesburg"],["Hopitaux Universitaires de Geneve (HUG)","Florian Charbonnier","瑞士","Genève","Genève"]]

序号	机构名称	主要研究者	国家	省（州）	城市

[["广州医科大学附属第一医院医学伦理委员会","同意","2025-02-14"]]

序号	名称	审查结论	批准日期/备案日期

进行中（尚未招募）

目标入组人数	国内: 120 ； 国际: 400 ；
已入组人数	国内: 登记人暂未填写该信息； 国际: 1 ；
实际入组总人数	国内: 登记人暂未填写该信息； 国际: 登记人暂未填写该信息；

第一例受试者签署知情同意书日期	国内：登记人暂未填写该信息；     国际：2025-03-28；
第一例受试者入组日期	国内：登记人暂未填写该信息；     国际：2025-04-30；
试验完成日期	国内：登记人暂未填写该信息；     国际：登记人暂未填写该信息；