TY - JOUR
T1 - Assessment of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation
T2 - Rationale and design of the PROMISE-AF phase II study
AU - Berlin, Sarah
AU - Goette, Andreas
AU - Summo, Luciana
AU - Lossie, Janine
AU - Gebauer, Alexander
AU - Al-Saady, Naab
AU - Calo, Leonardo
AU - Naccarelli, Gerald
AU - Schunck, Wolf Hagen
AU - Fischer, Robert
AU - Camm, A. John
AU - Dobrev, Dobromir
N1 - Funding Information:
Sarah Berlin, Luciana Summo, Janine Lossie, Alexander Gebauer, and Robert Fischer are employees of OMEICOS Therapeutics. Wolf Schunck is Board Director of OMEICOS Therapeutics. Andreas Goette has served as a consultant and speaker for Bayer Health Care, MSD, Sanofi Aventis, BMS/Pfizer, Daiichi Sankyo, Boehringer Ingelheim and OMEICOS Therapeutics. Dobromir Dobrev is member of Scientific Advisory Boards of OMEICOS Therapeutics, Acesion Pharma and Sanofi and received speaker’s fees for educational lectures from Boston Scientific, Novartis and Bristol-Myers Squibb. His laboratory executed research contracts for OMEICOS Therapeutics. Gerald V. Naccarelli has received the following (outside the submitted work): personal fees from Acesion, Correvio, Janssen, Milestone, OMEICOS Therapeutics, and Sanofi; grants from Janssen. Naab Al-Saady is an employee of Covance Inc. (study contract research organization). John Camm has received personal fees form Correvio, Sanofi, Acesion Pharma, OMEICOS Therapeutics, Huya, Milestone, and Incarda.
Funding Information:
The study is funded by OMEICOS Therapeutics GmbH. The authors are solely responsible for the design and conduct of the study as well as drafting and editing of the manuscript, and its final contents.
Funding Information:
We acknowledge the contributions and continuous support by. The Clinical Advisory Board Members of OMEICOS Therapeutics GmbH: L. Caló, MD, University Cattolica, Rome (Italy); A.J. Camm, MD, FRCP, University of London and Imperial College (United Kingdom); D. Dobrev, MD, FIACS, FISHR, University of Duisburg-Essen (Germany); A. Goette, MD, FEHRA, St. Vincenz-Hospital, Paderborn (Germany); G. Naccarelli, MD, FACC, FAHA, FHRS, Pennsylvania State University, Pennsylvania (USA). The Members of the Data Monitoring Committee (DMC): U. Tebbe, MD, B. Katgely, MD, and M. Klasser. The Members of the Insertable Cardiac Monitor Data Review Committee (ICM-DRC): F. Günther, MD, A. Ohler, MD, and W. Haverkamp, MD, from ExCard GmbH, Berlin (Germany)., We would also like to thank A. Busjahn (HealthTwist GmbH) for his support in sample size planning, R. Sroka (Semdatex GmbH) and D. Haverkamp (ExCard GmbH) in data management.
Publisher Copyright:
© 2020
PY - 2020/8
Y1 - 2020/8
N2 - 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 Ca2+-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.
AB - 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 Ca2+-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.
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U2 - 10.1016/j.ijcha.2020.100573
DO - 10.1016/j.ijcha.2020.100573
M3 - Article
C2 - 32685659
AN - SCOPUS:85087698852
SN - 2352-9067
VL - 29
JO - IJC Heart and Vasculature
JF - IJC Heart and Vasculature
M1 - 100573
ER -