Assessment of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation: Rationale and design of the PROMISE-AF phase II study
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-epoxyeicosatet...
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doaj-fea19d454d8e4a4aa7ba5fe2fa60d1af2020-11-25T02:42:13ZengElsevierInternational Journal of Cardiology: Heart & Vasculature2352-90672020-08-0129100573Assessment of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation: Rationale and design of the PROMISE-AF phase II studySarah Berlin0Andreas Goette1Luciana Summo2Janine Lossie3Alexander Gebauer4Naab Al-Saady5Leonardo Calo6Gerald Naccarelli7Wolf-Hagen Schunck8Robert Fischer9A.John Camm10Dobromir Dobrev11OMEICOS Therapeutics GmbH, Berlin, GermanyCardiology and Intensive Care Medicine, St. Vincenz-Hospital, Paderborn, Germany; Working Group Molecular Electrophysiology, University Hospital Magdeburg, Magdeburg, Germany; Corresponding author at: Institute of Pharmacology, University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany or St. Vincenz-Hospital GmbH, Am Busdorf 2, 33098 Paderborn, Germany.OMEICOS Therapeutics GmbH, Berlin, GermanyOMEICOS Therapeutics GmbH, Berlin, GermanyOMEICOS Therapeutics GmbH, Berlin, GermanyCovance Inc., Maidenhead, United KingdomDivision of Cardiology, Policlinico Casilino, 00169 Rome, ItalyHeart and Vascular Institute, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USAMax Delbrueck Center for Molecular Medicine, Berlin, GermanyOMEICOS Therapeutics GmbH, Berlin, GermanySt. George's University of London, London, United KingdomInstitute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany; Corresponding author at: Institute of Pharmacology, University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany or St. Vincenz-Hospital GmbH, Am Busdorf 2, 33098 Paderborn, Germany.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.http://www.sciencedirect.com/science/article/pii/S2352906720302712OMT-28Omega-3 epoxyeicosanoidAtrial fibrillationPhase II |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sarah Berlin Andreas Goette Luciana Summo Janine Lossie Alexander Gebauer Naab Al-Saady Leonardo Calo Gerald Naccarelli Wolf-Hagen Schunck Robert Fischer A.John Camm Dobromir Dobrev |
spellingShingle |
Sarah Berlin Andreas Goette Luciana Summo Janine Lossie Alexander Gebauer Naab Al-Saady Leonardo Calo Gerald Naccarelli Wolf-Hagen Schunck Robert Fischer A.John Camm Dobromir Dobrev Assessment of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation: Rationale and design of the PROMISE-AF phase II study International Journal of Cardiology: Heart & Vasculature OMT-28 Omega-3 epoxyeicosanoid Atrial fibrillation Phase II |
author_facet |
Sarah Berlin Andreas Goette Luciana Summo Janine Lossie Alexander Gebauer Naab Al-Saady Leonardo Calo Gerald Naccarelli Wolf-Hagen Schunck Robert Fischer A.John Camm Dobromir Dobrev |
author_sort |
Sarah Berlin |
title |
Assessment of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation: Rationale and design of the PROMISE-AF phase II study |
title_short |
Assessment of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation: Rationale and design of the PROMISE-AF phase II study |
title_full |
Assessment of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation: Rationale and design of the PROMISE-AF phase II study |
title_fullStr |
Assessment of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation: Rationale and design of the PROMISE-AF phase II study |
title_full_unstemmed |
Assessment of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation: Rationale and design of the PROMISE-AF phase II study |
title_sort |
assessment of omt-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation: rationale and design of the promise-af phase ii study |
publisher |
Elsevier |
series |
International Journal of Cardiology: Heart & Vasculature |
issn |
2352-9067 |
publishDate |
2020-08-01 |
description |
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. |
topic |
OMT-28 Omega-3 epoxyeicosanoid Atrial fibrillation Phase II |
url |
http://www.sciencedirect.com/science/article/pii/S2352906720302712 |
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