北京Volixibat胶囊II期临床试验-一项在原发性胆汁性胆管炎患者中评估Volixibat治疗胆汁淤积性瘙痒的疗效和安全性的随机、双盲、安慰剂对照研究(VANTAGE)

登记号	CTR20244920	试验状态	进行中
申请人联系人	Quynh Tran	首次公示信息日期	2024-12-27
申请人名称	Mirum Pharmaceuticals, Inc./ 赛纽仕医药信息咨询（北京）有限公司/ Halo Pharmaceutical Canada, Inc.

登记号	CTR20244920
相关登记号	暂无
药物名称	Volixibat胶囊
药物类型	化学药物
临床申请受理号	企业选择不公示
适应症	用于治疗原发性胆汁性胆管炎（PBC）患者的胆汁淤积瘙痒症
试验专业题目	一项在原发性胆汁性胆管炎患者中评估Volixibat治疗胆汁淤积性瘙痒的疗效和安全性的随机、双盲、安慰剂对照研究(VANTAGE)
试验通俗题目	一项在原发性胆汁性胆管炎患者中评估Volixibat治疗胆汁淤积性瘙痒的疗效和安全性的随机、双盲、安慰剂对照研究(VANTAGE)
试验方案编号	VLX-601	方案最新版本号	版本3
版本日期:	2023-08-03	方案是否为联合用药	否

申请人名称	[["Mirum Pharmaceuticals, Inc."],["赛纽仕医药信息咨询（北京）有限公司"],["Halo Pharmaceutical Canada, Inc."]]
联系人姓名	Quynh Tran	联系人座机	646-3002679	联系人手机号
联系人Email	quynh.tran@mirumpharma.com	联系人邮政地址	北京市-北京市-朝阳区建国门外大街2号院3号楼5层	联系人邮编	100020

主要目的：基于主要终点，评估 Volixibat 相较于安慰剂治疗 PBC 受试者瘙痒的疗效；次要目的：基于次要终点，评估 Volixibat 相较于安慰剂对 PBC 受试者胆汁淤积标志物改善的疗效。

试验分类	安全性和有效性	试验分期	II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	18岁(最小年龄)至 无上限 (最大年龄)
性别	男+女
健康受试者	无
入选标准	[["愿意并能够在筛选访视时提供签署的知情同意书，并遵守所有研究访视和要求，直至研究结束"],["男性或女性，筛选访视时年龄≥18 岁"],["具有以下≥2 项，证实 PBC 诊断符合 AASLD 指南na.筛选访视前≥6 个月首次发现 ALP 水平持续升高＞ULN 的病史（意识到 UDCA 治疗时 ALP 可能降低，因此不要求筛选时 ALP 持续升高）nb.记录 AMA 滴度阳性（免疫荧光滴度＞1:40 或酶联免疫吸附试验 M2 阳性）或 PBC 特异性自身抗体免疫荧光模式（多个核点和/或点状核缘）nc.非化脓性破坏性胆管炎和小叶间胆管破坏的组织学证据。既往可能在任何时间进行的肝脏活检"],["如果接受 UDCA 治疗的患者在筛选（访视 1）时符合以下标准之一，则允许入组：na.至少 6 周的稳定治疗，或 nb.至少结束治疗 6 周和随后由研究者确定临床稳定"],["如果在筛选（访视 1）时符合以下标准之一，则允许使用旨在解决胆汁淤积性瘙痒的全身药物治疗，具体包括但不限于贝特类、SSRI、利福平、加巴喷丁、考来烯胺和阿片类受体拮抗剂： na.至少6周的稳定治疗或 nb.结束治疗至少2周"],["在访视2前的连续2周内，平均每日成人ItchRO评分≥1"],["在访视2前的连续2周内，成人ItchRO每日日记条目的依从性≥70%"]]
排除标准	[["可能干扰PBC相关瘙痒严重程度评估的其他病因的慢性瘙痒"],["有失代偿性肝硬化或肝硬化并发症的证据。有代偿性肝硬化且肝合成功能保留且无并发症的患者符合资格"],["当前患有症状性胆石症或炎性胆囊疾病。在筛选访视前≥3个月有胆囊切除术史的患者可能有资格入组"],["累及回肠末端的小肠手术/切除史，可能破坏肠肝循环"],["有其他肝脏疾病的证据、病史或怀疑，包括但不限于(字数限制详见方案)"],["可能损害受试者参与研究所有方面的能力、混淆疗效和/或安全性评估或导致预期寿命大幅缩短的不稳定和/或严重医学疾病"],["本研究定义的中度饮酒，即在筛选访视前24周内，女性和男性平均每天分别饮用＞1和＞2标准饮料"],["筛选访视前24周内的药物滥用或药物筛查结果呈阳性，除非可以通过药物处方进行解释。如果研究者认为结果反映了可能损害受试者参与研究能力的行为模式，则将根据阳性药物筛查排除受试者"],["HIV 抗体阳性"],["特定的具有临床意义的 ECG 异常，包括但不限于(字数限制详见方案)"],["中心实验室提供的筛选访视期间收集的以下任何实验室参数的结果(字数限制详见方案)"],["无法遵守或满足第6.8.1节中列出的筛选前选定允许合并用药的最低时间要求"],["筛选访视前至少8周内他汀类药物给药不稳定"],["筛选访视前8周内使用奥贝胆酸治疗"],["筛选访视前4周内使用IBAT抑制剂"],["在筛选访视前4周或5倍半衰期内使用研究方案中列出的禁用药物，以较长者为准"],[".妊娠或哺乳期女性。研究方案中概述了定义有生育能力的具体标准和可接受的避孕方法"],["已知对 Volixibat 或其辅料过敏/超敏"],["有研究者认为可能损害知情同意的有效性、损害受试者的安全性、导致不依从研究方案或无法进行研究程序的不依从治疗方案、不可靠、病况、精神不稳定或认知受损病史"],["在筛选访视前4周内或（如适用）5倍半衰期内（以较长者为准）参加干预性临床研究。始终遵守适用于特定合并用药的其他合格性标准"],["受试者与参与本研究实施的研究中心工作人员有依赖关系或有直系亲属（例如，配偶、父母、子女或兄弟姐妹）或受试者是研究中心工作人员"]]

试验药	[["中文通用名:Volixibat胶囊 英文通用名:Volixibatcapsules 商品名称:NA","剂型:胶囊剂 规格:5mg 用法用量:在双盲研究治疗期间，将给予研究药物（安慰剂或Volixibat）（4粒胶囊，口服）BID（早晚各一次）。在LTE期间，将给予Volixibat（20mg或80mg）（4粒胶囊，口服）BID（早晚各一次） 用药时程:24周双盲研究治疗期"]] 序号 名称 用法
对照药	[["中文通用名:Volixibat安慰剂 英文通用名:VolixibatPlacebo 商品名称:NA","剂型:胶囊剂 规格:5mg 用法用量:在双盲研究治疗期间，将给予研究药物（安慰剂或Volixibat）（4粒胶囊，口服）BID（早晚各一次）。在LTE期间，将给予Volixibat（20mg或80mg）（4粒胶囊，口服）BID（早晚各一次） 用药时程:24周双盲研究治疗期"]] 序号 名称 用法

主要终点指标及评价时间

[["从第 12 周至第 24 周，成人 ItchRO 评分较基线的平均变化与每周平均每日瘙痒评分的平均值","12周（从第 12 周至第 24 周）","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

[["第 24 周血清胆汁酸 (sBA) 水平较基线的平均变化","24周","有效性指标"],["第 24 周总胆红素水平较基线平均值的变化","24周","有效性指标"],["第 24 周 ALP 水平较基线平均值的变化","24周","有效性指标"],["第 24 周原发性胆汁性胆管炎生活质量指标 (PBC-40) 较基线的变化","24周","有效性指标"],["第 24 周患者报告结局测量信息系统 (PROMIS？) 疲乏评分较基线的变化","24周","有效性指标"],["第 24 周 PROMIS 睡眠评分较基线的变化","24周","有效性指标"],["自基线至第 24 周每日成人 ItchRO 每周平均评分降低≥2 分的受试者比例","24周","有效性指标"],["治疗中发生的不良事件、严重不良事件、临床关注事件和导致停用研究药物的不良事件发生率","24周","安全性指标"],["临床相关实验室检查异常的发生率","24周","安全性指标"]] 序号 指标 评价时间 终点指标选择

1	姓名	贾继东	学位	博士后	职称	正高级
	电话	13501378269	Email	jia_jd@ccmu.edu.cn	邮政地址	北京市-北京市-西城区永安路95号
	邮编	100050	单位名称	首都医科大学附属北京友谊医院

[["首都医科大学附属北京友谊医院","贾继东","中国","北京市","北京市"],["福建医科大学孟超肝胆医院","黄祖雄","中国","福建省","福州市"],["浙江大学医学院附属邵逸夫医院","吕芳芳","中国","浙江省","杭州市"],["首都医科大学附属北京佑安医院","徐斌","中国","北京市","北京市"],["吉林大学第一医院","金清龙","中国","吉林省","长春市"],["Gordon and Leslie Diamond Health Care Centre","Chahal, Daljeet","加拿大","British Columbia","Vancouver"],["University of Colorado Anschutz","Forman, Lisa","美国","Colorado","Aurora"],["Cedars-Sinai Medical Center CSMC - Comprehensive Transplant Center CTC","Ayoub, Walid","美国","California","West Hollywood"],["University of Miami/Schiff Center for Liver Diseases","Levy, Cynthia","美国","Florida","Miami"],["Beth Israel Deaconess Medical Center","Bonder, Alan","美国","Massachusetts","Boston"],["University of Iowa Hospitals and Clinic","Sanchez, Antonio","美国","Iowa","Iowa City"],["Loyola University Medical Center","Von Roenn, Natasha","美国","Illinois","Maywood"],["Advanced Research Institute Inc.","Freedland, Curtis Israel","美国","Florida","New Port Richey"],["Tampa General Hospital","Kemmer, Nyingi","美国","Florida","Tampa"],["University of Utah Health - University of Utah Hospital","Gallegos-Orozco, Juan","美国","Utah","Salt Lake City"],["CHI Health Clinic (Alegent Creighton Clinic) - Gastroenterology - Bergan","Mukherjee, Sandeep","美国","Nebraska","Omaha"],["Liver Associates of Texas","Ankoma-Sey, Victor","美国","Texas","Houston"],["Mayo Clinic","Eaton, John","美国","Massachusetts","Rochester"],["Covenant Research LLC","Neff, Guy","美国","Florida","Sarasota"],["Cleveland Clinic","Chiang, Dian","美国","Ohio","Cleveland"],["IHS Health","Lateef, Syed","美国","Florida","Kissimmee"],["UF Health Gastroenterology - JTB Kernan","Agrawal, Neha","美国","Florida","Jacksonville"],["Impact Research","Gunn, Nadege","美国","Texas","Waco"],["Soma Clinical Trials","Elgouhari, Hesham","美国","Texas","Denison"],["LSU Health Sciences Center","Cai, Qiang","美国","Louisiana","Shreveport"],["Covenant Research and Clinics","Neff, Guy","美国","Florida","Fort Myers"],["Albert Einstein Healthcare Network","Thapar, Manish","美国","Commonwealth of Pennsylvania","Philadelphia"],["Georgetown University Medical Center","Smith, Coleman","美国","DC","Washington"],["Galen Hepatology","Patel, Chirag","美国","State of Tennessee","Hixson"],["Bon Secours Liver Institute of Hampton Roads","Shiffman, Mitchell","美国","Commonwealth of Virginia","Newport News"],["Liver Institute Northwest","Kowdley, Kris","美国","State of Washington","Seattle"],["UF Hepatology Research at CTRB","Firpi-Morell, Roberto","美国","Florida","Gainesville"],["Southeast Clinical Research Center","Perez, Pablo","美国","Georgia","Dalton"],["Northwestern University","Boike, Justin","美国","Illinois","Chicago"],["Ochsner Health - Ochsner Medical Center - Baton Rouge","Samant, Hrishikesh","美国","Louisiana","Baton Rouge"],["Amel Med LLC","Khaja, Masi","美国","Texas","Austin"],["Bon Secours Richmond Community Hospital LLC d/b/a Bon Secours Liver Institute of Richmond","Shiffman, Mitchell","美国","Commonwealth of Virginia","Richmond"],["Science 37","Weinstein, Debra","美国","California","Culver City"],["Kings College Hospital","Heneghan, Michael","英国","London","London"],["Nottingham University Hospitals NHS Trust","Venkatachalapathy, Suresh Vasan","英国","Nottinghamshire","Nottingham"],["Belfast Health & Social Care Trust","McCorry, Roger","英国","Northern Ireland","Belfast"],["University Hospital Southampton NHS Foundation Trust","Patel, Janisha","英国","Hampshire","Southampton"],["Rabin Medical Center","Braun, Marius","以色列","Tel Aviv-Yafo","Petach Tikva"],["Hillel Yaffe Medical Center","Abu-Mouch, Saif","以色列","Central District","Hadera"],["Carmel medical Center","Zuckerman, Eli","以色列","Haifa","Haifa"],["Rambam Health Care Campus - Rambam Medical Center","Veitsman, Ella","以色列","Haifa","Haifa"],["Sheba Medical Center at Tel Hashomer","Zigmond, Ehud","以色列","Tel Aviv-Yafo","Ramat Gan"],["Galilee Medical Center","Assy, Nimer","以色列","Northern District","Zefat"],["Hadassah Ein-Karem Medical Center - Liver unit","Safadi, Rifaat","以色列","Jeru salem","Jerusalem"],["UZ Gent","Verhelst, Xavier","比利时","NA","Gent"],["Universitatsklinikum Schleswig-Holstein","Guenther, Rainer","德国","Schleswig-Holstein","Kiel"],["Universitaets Klinikum Frankfurt - Zentrum der Inneren Medizin - Medizinische Klinik 1","Sprinzl, Kathrin","德国","Hessen","Frankfurt am Main"],["Universitaetsklinikum Tuebingen","Berg, Christoph","德国","Baden-Wuerttemberg","Tuebingen"],["Medizinische Hochschule Hannover","Wedemeyer, Heiner","德国","Lower Saxony","Hannover"],["Klinikum Chemnitz gGmbH","Wissniowski, Till","德国","Free State of Saxony","Chemnitz"],["University Hospital Munster","Trebicka, Jonel","德国","Schleswig-Holstein","Muenster"],["St. Josefs-Hospital Wiesbaden","Sarrazin, Christoph","德国","Hessen","Wiesbaden"],["CHRU de Lille","Louvet, Alexandre","法国","Hauts-de-France","Lille"],["CHU Paris Est - Hopital Saint Antoine","Corpechot, Christophe","法国","ile-de-France","Paris"],["CHU de Strasbourg-Hopital Civil","Habersetzer, Francois","法国","Grand Est","Strasbourg cedex"],["Hopital Paul-Brousse","COILLY, Audrey","法国","ile-de-France","Villejuif"],["Centre Hospitalier Universitaire de Nice Hopital l Archet","Tran, Albert","法国","Provence-Alpes-Cote d’Azur","Nice Cedex 3"],["Centre Hospitalier Universitaire Grenoble Alpes (CHUGA)","Hilleret, Marie Noelle","法国","Nouvelle-Aquitaine","La Tronche"],["Universita Politecnica delle Marche - Ospedali Riuniti","Marzioni, Marco","意大利","Torrette","Ancona"],["Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico","Lampertico, Pietro","意大利","Lombardia","Milano"],["Universita Degli Studi Di Padova - Azienda Ospedaliera Di Padova","Cazzagon, Nora","意大利","Veneto","Padova"],["Istituto Clinico Humanitas","Lleo de Nalda, Ana","意大利","Milan","Rozzano"],["ASST Monza-Ospedale San Gerardo","Invernizzi, Pietro","意大利","Lombardia","Monza (MB)"],["Azienda Ospedaliero Universitaria Pisana","Brunetto, Maurizia Rossana","意大利","Tuscany","Pisa"],["ASST Grande Ospedale Metropolitano Niguarda","Vigano, Raffaella","意大利","Milan","Milano"],["Erasmus MC","Van Der Meer, Adriaan","荷兰","South Holland","Rotterdam"],["Amsterdam University Medical Centers","de Boer, Ynto Sjoerd","荷兰","North Holland","Amsterdam"],["Hospital Clinic de Barcelona (Hospital Clinic i Provincial)","Rodriguez Tajes, Sergio","西班牙","Catalunya","Barcelona"],["Parc Tauli Sabadell Hospital Universitari","Vergara, Mercedes","西班牙","Catalunya","Sabadell"],["Hospital General Universitario Gregorio Maranon","Salcedo, Magdalena","西班牙","Catalunya","Sabadell"],["Toranomon Hospital","Akuta, Norio","日本","Tokyo","Minato-ku"],["Juntendo University Hospital","Ikejima, Kenichi","日本","Tokyo","Bunkyo-ku"]]

序号	机构名称	主要研究者	国家	省（州）	城市

[["首都医科大学附属北京友谊医院伦理委员会","修改后同意","2024-10-21"],["首都医科大学附属北京友谊医院伦理委员会","同意","2024-11-06"]]

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: 15 ； 国际: 180 ；
已入组人数	国内: 登记人暂未填写该信息； 国际: 90 ；
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：2021-11-11；
第一例受试者入组日期	国内：登记人暂未填写该信息；     国际：2022-04-18；
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；