Berlin Sarah, Goette Andreas, Summo Luciana, Lossie Janine, Gebauer Alexander, Al-Saady Naab, Calo Leonardo, Naccarelli Gerald, Schunck Wolf-Hagen, Fischer Robert, Camm A John, Dobrev Dobromir
OMEICOS Therapeutics GmbH, Berlin, Germany.
Cardiology and Intensive Care Medicine, St. Vincenz-Hospital, Paderborn, Germany.
Int J Cardiol Heart Vasc. 2020 Jul 10;29:100573. doi: 10.1016/j.ijcha.2020.100573. eCollection 2020 Aug.
We designed a placebo controlled, double-blind, randomized, dose-finding phase II study on OMT-28 in the maintenance of sinus rhythm after electrical cardioversion (DCC) in patients with persistent atrial fibrillation (PROMISE-AF). OMT-28 is a first-in-class, synthetic analog of 17,18-epoxyeicosatetetraenoic acid, a bioactive lipid mediator generated by cytochrome P450 enzymes from the omega-3 fatty acid eicosapentaenoic acid. OMT-28 improves Ca-handling and mitochondrial function in cardiomyocytes and reduces pro-inflammatory signaling. This unique mode of action may provide a novel approach to target key mechanism contributing to AF pathophysiology. In a recent phase I study, OMT-28 was safe and well tolerated and showed favorable pharmacokinetics. The PROMISE-AF study (NCT03906799) is designed to assess the efficacy (primary objective), safety, and population pharmacokinetics (secondary objectives) of three different doses of OMT-28, administered once daily, versus placebo until the end of the follow-up period. Recruitment started in March 2019 and the study will include a total of 120 patients. The primary efficacy endpoint is the AF burden (% time with any AF), evaluated over a 13-week treatment period after DCC. AF burden is calculated based on continuous ECG monitoring using an insertable cardiac monitor (ICM). The primary efficacy analysis will be conducted on the modified intention-to-treat (mITT) population, whereas the safety analysis will be done on the safety population. Although ICMs have been used in other interventional studies to assess arrhythmia, PROMISE-AF will be the first study to assess antiarrhythmic efficacy and safety of a novel rhythm-stabilizing drug after DCC by using ICMs.
我们设计了一项安慰剂对照、双盲、随机、剂量探索性II期研究，以评估OMT-28在持续性房颤患者（PROMISE-AF）电复律（DCC）后维持窦性心律的效果。OMT-28是一种一流的17,18-环氧二十碳四烯酸合成类似物，17,18-环氧二十碳四烯酸是一种生物活性脂质介质，由细胞色素P450酶从ω-3脂肪酸二十碳五烯酸生成。OMT-28可改善心肌细胞的钙处理和线粒体功能，并减少促炎信号传导。这种独特的作用方式可能为针对房颤病理生理学关键机制提供一种新方法。在最近的一项I期研究中，OMT-28安全且耐受性良好，并显示出良好的药代动力学特性。PROMISE-AF研究（NCT03906799）旨在评估三种不同剂量的OMT-28（每日给药一次）与安慰剂相比，在随访期结束前的疗效（主要目标）、安全性和群体药代动力学（次要目标）。招募工作于2019年3月开始，该研究将共纳入120名患者。主要疗效终点是房颤负荷（任何房颤发生时间的百分比），在DCC后的13周治疗期内进行评估。房颤负荷通过使用植入式心脏监测器（ICM）进行连续心电图监测来计算。主要疗效分析将在改良意向性治疗（mITT）人群中进行，而安全性分析将在安全人群中进行。尽管ICM已在其他介入性研究中用于评估心律失常，但PROMISE-AF将是第一项使用ICM评估DCC后新型心律稳定药物抗心律失常疗效和安全性的研究。
