一、题目和背景信息
| 登记号 |
CTR20253079 |
| 相关登记号 |
暂无
|
| 药物名称 |
BMS-986435片 |
| 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 |
射血分数保留的心力衰竭 |
| 试验专业题目 |
一项在射血分数保留的心力衰竭 (HFpEF) 受试者中评价 BMS-986435/MYK-224 的安全性、耐受性、药代动力学和药效学的2A期、双盲、随机、安慰剂对照、多中心研究 |
| 试验通俗题目 |
MYK-224 治疗射血分数保留的心力衰竭 (HFpEF) |
| 试验方案编号 |
CV0291001 |
方案最新版本号
|
方案修订案03 |
| 版本日期: |
2025-03-12 |
方案是否为联合用药 |
否 |
二、申请人信息
| 申请人名称 |
[["Bristol-Myers Squibb Company"],["百时美施贵宝（中国）投资有限公司"],["Quotient Sciences - Philadelphia, LLC；Bristol Myers Squibb Co."],["Bristol Myers Squibb Co.; Fisher Clinical Services Inc"]] |
| 联系人姓名 |
周杨明 |
联系人座机 |
021-23218100 |
联系人手机号 |
13631337376 |
| 联系人Email |
yangming.zhou@bms.com |
联系人邮政地址 |
上海市-上海市-静安区南京西路1717号17楼 |
联系人邮编 |
200040 |
三、临床试验信息
1、试验目的
主要目的：评估MYK-224在HFpEF受试者中的安全性和耐受性。
次要目的：评估MYK-224在HFpEF受试者中的PK。
探索性目的：
评估MYK-224的PK特征以及与PK差异相关的潜在内在/外在特征；
评估MYK-224对HFpEF受试者的心脏生物标志物水平的影响；
评估MYK-224对HFpEF受试者心脏功能的影响；
探索MYK-224的PK/PD关系；
评估MYK-224对HFpEF受试者的 NYHA 功能分级的影响；
探索MYK-224对HFpEF受试者的患者报告健康状态（症状和身体限制）的影响
评估达到有意义的患者内KCCQ-23 CSS变化的患者比例
2、试验设计
| 试验分类 |
其他
其他说明:安全性、耐受性、药代动力学和药效学 |
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
|
3、受试者信息
| 年龄 |
40岁(最小年龄)至
85岁(最大年龄) |
| 性别 |
男+女
|
| 健康受试者 |
无
|
| 入选标准 |
[["签署书面知情同意书。"],["筛选时NYHA 心功能分级为 II 级或 III 级。"],["筛选时NT-proBNP 或BNP升高。"],["筛选时 经以下至少一项超声心动图证据证实，患有器质性或功能性心脏病：左心室充盈压升高或 左心房扩大或 左心室肥厚。"],["超声心动图图像质量足以支持在整个研究期间获取LVEF，且筛选时LVEF≥55%。"],["根据当地心力衰竭指南确诊 HFpEF。"],["受试者签署知情同意书时年龄必须为 40 岁（含）至 85 岁（含）。"],["女性受试者不得处于妊娠或哺乳期。无生育能力的女性受试者必须有书面证明。有生育能力的女性受试者和与有生育能力的女性有活跃性关系的男性受试者必须同意在研究期间采取满足要求的高效避孕措施。"]]
|
| 排除标准 |
[["已知诊断为梗阻性或遗传性肥厚型心肌病 (HCM)，或已知患有浸润性或贮积性疾病，如心脏淀粉样变性、法布里病或努南综合征。"],["有 LVEF≤40%既往史。"],["筛选时检测到阵发性、间歇性心房颤动 (AF)。"],["持续性或永久性 AF，未接受抗凝治疗和/或未充分控制心率达筛选前至少4周。"],["具有研究者认为对受试者的安全构成风险的心电图异常（如病窦综合征、三度房室传导阻滞或未植入起搏器的莫氏 II 型房室传导阻滞）。"],["在过去3个月内患有：(1) 已知未接受血运重建的严重阻塞性冠状动脉疾病或 (2) 急性冠脉综合征。"],["筛选时存在重度主动脉瓣狭窄或反流、血流动力学显著的二尖瓣狭窄或重度二尖瓣或三尖瓣反流（均由研究者判断）。"],["患有任何急性或严重合并疾病（如重大感染或血液、肾脏、代谢、胃肠道或内分泌功能障碍）或计划在研究治疗期间进行任何重大心脏手术，根据研究者的判断，可能导致提前终止参与研究或干扰本研究疗效和安全性评估的测量或解读。"],["患有重度慢性阻塞性肺疾病或其他重度肺部疾病，需要家庭吸氧，或确定在12个月内因肺部疾病失代偿而住院。"],["具有记录的任何活动性或疑似恶性肿瘤或筛选前2年内存在具有临床意义的恶性疾病史。"],["既往或现患任何其他具有临床意义的病症、状况或疾病（上述情况除外），经研究者或研究医学监查员判断，认为会对受试者的安全构成风险或干扰研究评价、程序或完成。"],["筛选前30天内出现需要静脉注射 (IV) 利尿剂、IV 正性肌力药、IV血管扩张剂或左心室辅助装置的急性失代偿性心力衰竭事件。"],["处于妊娠或哺乳期的女性"],["筛选前7天或5个半衰期（以较长者为准）至研究结束 (EOS) 访视期间，禁止使用强效 CYP3A4 抑制剂或诱导剂（如圣约翰草）。"],["既往接受过或合并接受心脏毒性药物治疗，如蒽环类药物（如多柔比星）或类似药物。"],["受试者应正在接受稳定的当地现行指南推荐的 HFpEF 背景治疗。筛选前 4 周内至随机当日，不得开始使用、停用 HFpEF 治疗药物或调整其剂量。随机后，背景药物治疗也应保持稳定，除非因医学原因需要调整。"],["从随机前15天至研究结束 (EOS) 访视，禁止使用任何中药或植物制剂，除非需要使用这些药物治疗AE，但前提是需要经过医学监查员讨论和批准。"],["血红蛋白 < 10.0 g/dL。"],["BMI ≥ 45.0 kg/m2。"],["经体型校正的估算肾小球滤过率 (eGFR) < 30 mL/min/1.73m2（根据肾病饮食调整研究 [MDRD] 公式计算）。"],["丙氨酸氨基转移酶 (ALT) 或天门冬氨酸氨基转移酶 (AST) ≥ 3 x 实验室检查参考范围上限。超出正常限值的任何其他安全性实验室参数应在入组前与研究医学监查员讨论。"],["已知患有活动性人类免疫缺陷病毒 (HIV)、丙型肝炎病毒 (HCV) 或乙型肝炎病毒 (HBV) 感染。"],["在筛选或随机时已知患有活动性 2019 冠状病毒 (COVID-19) 感染和/或其他急性呼吸道感染。"],["已知对玛伐凯泰或相关化合物有过敏史。"],["已知确证对BMS-986435/MYK-224制剂的任何成分或β-内酰胺类（如青霉素、头孢菌素、碳青霉烯类或单环β-内酰胺类）过敏。"],["方案中规定的其他排除标准。"]]
|
4、试验分组
| 试验药 |
| 序号 |
名称 |
用法 |
[["中文通用名:BMS-986435片
英文通用名:BMS-986435Tablet
商品名称:NA","剂型:片剂
规格:5mg/片
用法用量:分为4组：剂量组1、剂量组2、剂量组3及安慰剂组。每日1次，每次3片（根据组别不同使用不同规格活性药物或安慰剂的组合）
用药时程:共用药20周"],["中文通用名:BMS-986435片
英文通用名:BMS-986435Tablet
商品名称:NA","剂型:片剂
规格:10mg/片
用法用量:分为4组：剂量组1、剂量组2、剂量组3及安慰剂组。每日1次，每次3片（根据组别不同使用不同规格活性药物或安慰剂的组合）
用药时程:共用药20周"],["中文通用名:BMS-986435片
英文通用名:BMS-986435Tablet
商品名称:NA","剂型:片剂
规格:20mg/片
用法用量:分为4组：剂量组1、剂量组2、剂量组3及安慰剂组。每日1次，每次3片（根据组别不同使用不同规格活性药物或安慰剂的组合）
用药时程:共用药20周"]]
|
| 对照药 |
| 序号 |
名称 |
用法 |
[["中文通用名:BMS-986435片5mg/10mg对应安慰剂
英文通用名:PlaceboforBMS-986435Tablet5mg/10mg
商品名称:NA","剂型:片剂
规格:不适用
用法用量:分为4组：剂量组1、剂量组2、剂量组3及安慰剂组。每日1次，每次3片（根据组别不同使用不同规格活性药物或安慰剂的组合）
用药时程:共用药20周"],["中文通用名:BMS-986435片20mg对应安慰剂
英文通用名:PlaceboforBMS-986435Tablet20mg
商品名称:NA","剂型:片剂
规格:不适用
用法用量:分为4组：剂量组1、剂量组2、剂量组3及安慰剂组。每日1次，每次3片（根据组别不同使用不同规格活性药物或安慰剂的组合）
用药时程:共用药20周"]]
|
5、终点指标
| 主要终点指标及评价时间 |
| 序号 |
指标 |
评价时间 |
终点指标选择 |
[["TEAE、SAE 和导致治疗终止的 AE 的发生率","整个研究期间","安全性指标"]]
|
| 次要终点指标及评价时间 |
| 序号 |
指标 |
评价时间 |
终点指标选择 |
[["按访视对血浆浓度进行总结","从基线至第20周（或提前终止）","有效性指标+安全性指标"]]
|
四、研究者信息
1、主要研究者信息
| 1 |
姓名 |
王建安 |
学位 |
医学博士 |
职称 |
院士 |
| 电话 |
13805786328 |
Email |
wang_jian_an@vip.tom.com |
邮政地址 |
浙江省-杭州市-解放路88号 |
| 邮编 |
310009 |
单位名称 |
浙江大学医学院附属第二医院 |
2、各参加机构信息
| 序号 |
机构名称 |
主要研究者 |
国家 |
省（州） |
城市 |
[["浙江大学医学院附属第二医院","王建安","中国","浙江省","杭州市"],["中南大学湘雅二医院","彭道泉","中国","湖南省","长沙市"],["河南科技大学第一附属医院","杜来景","中国","河南省","洛阳市"],["广东省人民医院","荆志成","中国","广东省","广州市"],["北京大学协和医院","田庄","中国","北京市","北京市"],["Instituto de Investigaciones Clínicas Zárate","Ivana Stude","阿根廷","Buenos Aires","Zárate"],["Instituto Médico DAMIC","Jimena María ,Martinez","阿根廷","Córdoba","Córdoba"],["Corporación Médica de General San Martín","Rodolfo,Ahuad Guerrero","阿根廷","Buenos Aires","General San Martín"],["Centro de Especialidades Médicas CEMEDIC","Claudio,Majul","阿根廷","Ciudad Autónoma de BuenosAires","Ciudad Autónoma de Buenos Aires"],["Instituto de Cardiología SRL","Lilia,Lobo Marquez","阿根廷","Tucumán","San Miguel De Tucumán"],["Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno CEMIC-Galván 4102","Jorge,Thierer","阿根廷","Ciudad Autónoma de BuenosAires","Ciudad Autónoma Buenos Aires"],["Centro Cardiovascular Salta-Mariano Boedo 60","Ricardo,León de la Fuente","阿根廷","Salta","Salta"],["Instituto Cardiovascular de Rosario - ICR","Alejandro,Meirino","阿根廷","Santa Fe","Rosario"],["Sanatorio Duarte Quirós","Hugo,Colombo","阿根廷","NA","Córdoba"],["Clínica Privada Del Prado Sociedad de Responsabilidad Limitada","Lilia,Schiavi","阿根廷","Córdoba","Córdoba"],["Centro de Investigaciones Clínicas Del Litoral SRL","Miguel,Hominal (son)","阿根廷","Santa Fe","Santa Fe"],["Hamilton General Hospital","Catherine，Demers","加拿大","Ontario","Hamilton"],["Medicus MFC Inc.","Gordon，Moe","加拿大","Ontario","Toronto"],["Kaplan Medical Center","Sorel，Goland","以色列","NA","Rehovot"],["Rambam Health Care Campus – PPDS","Oren，Caspi","以色列","Haifa","Haifa"],["Hadassah Medical Center- Ein Kerem - PPDS","Donna，Zwas","以色列","Yerushalayim","Jerusalem"],["Rabin Medical Center - PPDS","Tuvia，Ben-Gal","以色列","HaMerkaz","Petah Tikva"],["Soroka University Medical Centre","Hilmi，Alnsasra","以色列","NA","Be'er Sheva"],["Shamir Medical Center","Avishay，Grupper","以色列","NA","Be'er - Ya'akov"],["Shaare Zedek Medical Center","Tal，Hasin","以色列","Yerushalayim","Jerusalem"],["ZIV Medical Center","Majdi，Halabi","以色列","NA","Safed"],["Okayama Rosai Hospital","Mitsuru，Munemasa","日本","Okayama","Okayama-Shi"],["Hyogo Prefectural Harima-Himeji General Medical Center","Tomofumi，Takaya","日本","Hyogo","Himeji-Shi"],["Kishiwada Tokushukai Hospital","Satoshi，Kuroyanagi","日本","osaka","Kishiwada-Shi"],["National Hospital Organization Kanazawa Medical Center","Takahiro，Saeki","日本","Isikawa","Kanazawa-shi"],["Takatsuki Red Cross Hospital","Haruhiko，Onaka","日本","osaka","Takatsuki-Shi"],["The Catholic University of Korea, Seoul St. Mary's Hospital","Jong-Chan，Youn","韩国","Seoul Teugbyeolsi","Seoul"],["Inha University Hospital","Sung-Hee，Shin","韩国","NA","Incheon"],["Seoul National University Hospital","Hyung-Kwan，Kim","韩国","NA","Seoul"],["Chonnam National University Hospital","Kye Hun，Kim","韩国","Gwangju Gwang'yeogsi","Gwangju"],["Chungnam National University Hospital","Jae-Hyeon，Park","韩国","Daejeon Gwang'yeogsi","Daejeon"],["Severance Hospital Yonsei University Health System","Seok-Min，Kang","韩国","Seoul Teugbyeolsi","Seoul"],["Pusan National University Hospital","Jung-Hyun，Choi","韩国","Busan Gwangyeogsi","Busan"],["Keimyung University Dongsan Hospital","In-Cheol，Kim","韩国","Daegu Gwang'yeogsi","Daegu"],["Seoul National University Bundang Hospital","Goo-Yeong，Cho","韩国","Gyeonggido","Seongnam-si"],["Samsung Medical Center","Sang-Chol，Lee","韩国","Seoul Teugbyeolsi","Seoul"],["John Radcliffe Hospital","Andrew，Lewis","英国","Oxfordshire","Oxford"],["Northwick Park Hospital","Jaymin，Shah","英国","NA","Harrow"],["New Cross Hospital","Sandeep，Hothi","英国","NA","Wolverhampton"],["University Hospital of North Tees","Paul，Davison","英国","NA","Stockton-On-Tees"],["North Tyneside General Hospital","Thomas，Green","英国","NA","North Shields"],["Leeds General Infirmary - PPDS","Andrew，Walker","英国","Yorkshire","Leeds"],["St Thomas' Hospital","Rebekah，Schiff","英国","NA","London"],["Ninewells Hospital - PPDS","Annamaria，Choy","英国","NA","Dundee"],["Bristol Royal Infirmary","Eva，Sammut","英国","NA","Bristol"],["Tennessee Center for Clinical Trials","Dinesh Gupta","美国","Tennessee","Tullahoma"],["University of Alabama at Birmingham","Pankaj Arora","美国","Alabama","Birmingham"],["Infinite Clinical Research","Sander Fernandez","美国","Florida","Miami"],["Bluhm Cardiovascular Institute of Northwestern","Ravi Patel","美国","Illinois","Chicago"],["Chicago Medical Research, LLC","Suhail Khadra","美国","Illinois","Hazel Crest"],["Weill Cornell Medicine","Parag Goyal","美国","New York","New York"],["Angiocardiac Care of Texas - PA - PPDS","Amin Karim","美国","Texas","Houston"],["South Oklahoma Heart Research","Naeem Tahirkheli","美国","Oklahoma","Oklahoma City"],["St. Louis Heart and Vascular","Harvey Serota","美国","Missouri","Saint Louis"],["Ascension Medical Group St. Vincent - Indianapolis Heart Care","Ashwin Ravichandran","美国","Indiana","Indianapolis"],["University of Texas Southwestern Medical Center","Ambarish Pandey","美国","Texas","Dallas"],["University of Rochester Medical Center - PPDS","Christopher Cove","美国","New York","Rochester"],["Capital Cardiology Associates","Eugene Pashkovetsky","美国","New York","Albany"],["Rochester General Hospital Center for Clinical Research","Vishal Parikh","美国","New York","Rochester"],["Ascension St. Vincent’s Riverside Hospital","Nima Taghipour","美国","Florida","Jacksonville"],["Abington Memorial Hospital","Donald Haas","美国","Pennsylvania","Abington"],["Laurelton Heart Specialist PC - MyClinical - PPDS","Olakunle Akinboboye","美国","New York","Rosedale"],["Duke Cardiology Clinic","Marat Fudim","美国","North Carolina","Durham"],["Colorado Heart and Vascular","McHale Anderson","美国","Colorado","Lakewood"],["University of Miami FL Miller School of Medicine -1120 NW 14th St","Omar Wever-Pinzon","美国","Florida","Miami"],["Heart Hospital of Austin","Jonathan Ginns","美国","Texas","Austin"],["New York Presbyterian Brooklyn_","Shudhanshu Alishetti","美国","New York","Brooklyn"]]
五、伦理委员会信息
| 序号 |
名称 |
审查结论 |
批准日期/备案日期 |
[["浙江大学医学院附属第二医院人体研究伦理委员会","同意","2025-06-09"],["浙江大学医学院附属第二医院人体研究伦理委员会","同意","2025-07-21"]]
六、试验状态信息
1、试验状态
进行中（尚未招募）
2、试验人数
| 目标入组人数 |
国内: 10 ；
国际: 160 ； |
| 已入组人数 |
国内: 登记人暂未填写该信息；
国际: 7 ； |
| 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； |
3、受试者招募及试验完成日期
| 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：2025-05-05； |
| 第一例受试者入组日期 |
国内：登记人暂未填写该信息；
国际：2025-05-22； |
|
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； |
