Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Cardiology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
BMJ Open. 2023 Jun 19;13(6):e071473. doi: 10.1136/bmjopen-2022-071473.
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.
肥厚型心肌病（HCM）是一种常见的原发性心肌疾病，通常由编码肌节蛋白的致病性基因突变引起。Mavacamten 是一种首创的心肌肌球蛋白变构抑制剂，在国际有症状梗阻性 HCM（oHCM）患者的临床试验中显示出疗效和安全性，但缺乏 Mavacamten 在中国人中的临床证据。
EXPLORER-CN 是一项多中心、III 期、随机、双盲、安慰剂对照的注册试验，旨在评估 Mavacamten 在有症状的 oHCM 中国成年人中的疗效和安全性。该研究将招募约 81 名有症状的 oHCM 患者。符合条件的参与者按 2:1 的比例随机分为每日一次口服 Mavacamten（起始剂量 2.5mg/天）或匹配安慰剂组，接受 30 周治疗，随后进行 48 周的长期扩展（LTE）期，所有受试者均接受活性治疗。在双盲、安慰剂对照期间，根据药代动力学（PK）/药效学（PD）参数调整 Mavacamten 剂量，在 LTE 期间仅根据 PD 调整剂量。主要疗效终点是通过多普勒超声心动图测量的基线至 30 周时的 Valsalva 左心室流出道（LVOT）峰值梯度的变化。次要疗效终点是静息 LVOT 峰值梯度的变化、达到 Valsalva LVOT 峰值梯度<30mmHg 或<50mmHg 的参与者比例、纽约心脏协会功能分类改善、堪萨斯城心肌病问卷临床综合评分的变化、心脏生物标志物和心脏磁共振评估的左心室质量指数的变化。LTE 终点将描述 Mavacamten 的长期安全性和疗效。
这项临床研究已获得中国医学科学院北京协和医学院药物临床试验伦理委员会的批准（编号：HS2021089）。将从每位参与者处获得书面知情同意。研究结果将发表在同行评议的期刊上，并在国内外会议上展示。
NCT05174416。
