Study design and rationale of EXPLORER-CN: a phase III, randomised, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of mavacamten in Chinese adults with symptomatic obstructive hypertrophic cardiomyopathy.
Study design and rationale of EXPLORER-CN: a phase III, randomised, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of mavacamten in Chinese adults with symptomatic obstructive hypertrophic cardiomyopathy.
复制标题
DOI：
10.1136/bmjopen-2022-071473
复制
发表时间：
2023-06-19
期刊：
影响因子：
2.9
通讯作者：
Han, Yaling
中科院分区：
文献类型：
--
作者：
Tian, Zhuang;Wang, Fang;Jin, Wei;Zhang, Qing;Zhou, Jingmin;Yang, Ping;Wang, Geng;Hsu, Peiwen;Sun, Jing;Zhang, Shuyang;Han, Yaling
肥厚型心肌病(HCM)是一种常见的由编码肌节蛋白的致病基因变异引起的原发心肌疾病。Mavacamten是一种一流的心脏特异性肌球蛋白变构抑制剂，已在国际临床试验中证明了对症状性梗阻性肥厚(OHCM)患者的有效性和安全性，但在中国人群中应用Mavacamten缺乏临床证据。探索者-CN是一项多中心、第三阶段、随机、双盲、安慰剂对照的注册试验，旨在评估马伐他汀在中国成人有症状的oHCM中的疗效和安全性。这项研究将招募大约81名患有症状性oHCM的参与者。符合条件的参与者以2：1的随机比例接受每日一次的口服马伐他汀(起始剂量为2.5mg.d)或匹配的安慰剂，为期30周，然后长期延长48周，对所有受试者进行积极治疗。在双盲、安慰剂控制期和在LTE期间仅使用PD的情况下，将根据药代动力学(PK)/药效学(PD)参数调整马卡坦的剂量。主要疗效终点是由多普勒超声心动图确定的Valsalva左心室流出道(LVOT)峰值梯度从基线到第30周的变化。次要疗效终点是静息左心室流出道峰值梯度的变化、参与者达到Valsalva左心室流出道峰值梯度<lt；30 或<；50 mm Hg的比例、纽约心脏协会功能级别的改善、堪萨斯城心肌病问卷临床总结评分的变化、心脏生物标志物和心脏磁共振评估的左心室重量指数。LTE终端将表征马伐他汀的长期安全性和有效性。本临床研究已获中国医学科学院、北京协和医院药物临床试验伦理委员会批准(参考号：HS2021089)。将从每个参与者那里获得书面知情同意。研究结果将发表在同行评议的期刊上，并在国内和国际会议上公布。NCT05174416。
Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease commonly caused by pathogenic genetic variants encoding sarcomere proteins. Mavacamten, a first-in-class allosteric inhibitor of cardiac-specific myosin, has demonstrated efficacy and safety in international clinical trials of patients with symptomatic obstructive HCM (oHCM) but clinical evidence for mavacamten in the Chinese population is lacking. EXPLORER-CN is a multicentre, phase III, randomised, double-blind, placebo-controlled registration trial to evaluate the efficacy and safety of mavacamten in Chinese adults with symptomatic oHCM. The study will enrol approximately 81 participants with symptomatic oHCM. Eligible participants are randomised 2:1 to receive once-daily, oral mavacamten (starting dose 2.5 mg/day), or matching placebo, for 30 weeks, followed by a long-term extension (LTE) period of 48 weeks with active treatment for all subjects. The mavacamten dose will be adjusted by pharmacokinetic (PK)/pharmacodynamic (PD) parameters during the double-blinded, placebo-controlled period and PD-only during the LTE period. The primary efficacy endpoint is change from baseline to week 30 in Valsalva left ventricular outflow tract (LVOT) peak gradient determined by Doppler echocardiography. Secondary efficacy endpoints are change in resting LVOT peak gradient, proportion of participants achieving a Valsalva LVOT peak gradient <30 or < 50 mm Hg, New York Heart Association functional class improvement, change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, cardiac biomarkers and left ventricular mass index evaluated by cardiac magnetic resonance. LTE endpoints will characterise the long-term safety and efficacy of mavacamten. This clinical study has been approved by the Drug Clinical Trial Ethics Committee of the Chinese Academy of Medical Sciences & Peking Union Medical College Hospital (reference number: HS2021089). Written informed consent will be obtained from each participant. The results will be published in peer-reviewed journals and presented during national and international conferences. NCT05174416.
登录
查看更多内容
影响因子：
39.3
作者：
Elliott, Perry M.;Anastasakis, Aris;Watkins, Hugh
通讯作者：
Watkins, Hugh
影响因子：
--
作者：
Hua TR;Zhang SY
通讯作者：
Zhang SY
影响因子：
5.9
作者：
Zou, YB;Song, L;Hui, RT
通讯作者：
Hui, RT
DOI：
10.3760/cma.j.issn.0253-3758.2017.12.005
发表时间：
2017-12-24
期刊：
Zhonghua xin xue guan bing za zhi
影响因子：
--
作者：
通讯作者：
--
影响因子：
158.5
作者：
Maron, MS;Olivotto, I;Maron, BJ
通讯作者：
Maron, BJ