Study on OMT-28 in Maintenance of Sinus Rhythm in Patients With Persistent Atrial Fibrillation (AF)

Atrial Fibrillation Clinical Trial

— PROMISE-AF  

Official title:

A Placebo-controlled, Double-blind, Randomized, Dose-finding Phase II Study on OMT-28 in MaIntenance of Sinus Rhythm After Electrical Cardioversion in Patients With Persistent Atrial Fibrillation (PROMISE-AF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03906799
• Other study ID #: OMT28-C0201
• Status: Completed
• Phase: Phase 2
• Start date: March 19, 2019
• Est. completion date: March 20, 2020

Study information

• Verified date: March 2019
• Source: Omeicos Therapeutics GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, dose-finding, placebo-controlled, parallel group, multicenter, phase II study to evaluate the efficacy, safety, and popPK of three different doses of OMT-28 given once daily versus placebo in patients with persistent AF.

Description:

This is a randomized, double-blind, dose-finding, placebo-controlled, parallel group, multicenter, phase II study to evaluate the efficacy, safety, and popPK of three different doses of OMT-28 given once daily versus placebo in patients with persistent AF. At randomization, the duration of the current episode of persistent AF must be shown to be greater than 7 days and not greater than 3 months, as confirmed by two ECGs (one ECG must be a 12-lead ECG) and further patient enquiry (including doctor visits, hospital admissions, symptom onset, etc.).

A sample size re-evaluation will be performed to avoid an underpowered study because of imprecise estimates for the study population or overoptimistic parameter estimates. Therefore, an interim analysis will re-evaluate sample size assumptions after approximately 15 patients per study arm (~50 % of planned sample) have completed the treatment phase (Visit 8) of the study. Predefined rules will govern the decision for adjustment of sample size.

Patients will be monitored for cardiac events throughout the study using an Implantable Cardiac Monitor (ICM). Safety will be monitored throughout the study. Blood samples will be collected in pre-specified windows for popPK analysis and at pre-specified timepoints for PK/PD analysis. Patients will be provided with a diary to record timing of drug administration and clinical symptoms while not on site. Diaries will be reviewed and checked for compliance at each non-resident visit to the clinical site.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. completion date: March 20, 2020
• Est. primary completion date: November 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Males or females between 18 and 85 years of age.

• Patients with persistent AF for > 7 days but = 3 months suitable for electrical DCC.

• Male patients must be surgically sterile for at least 90 days or will be required to use a male condom with spermicide, and will refrain from donating sperm from the time of the first dose until 90 days after the last dose of study medication.

• Females of childbearing potential (postmenarchal, not surgically sterile, premenopausal) will agree to follow contraception requirements from the time of signing the Informed Consent Form (ICF) until 90 days after the last administration of study drug.

• Willing and able to give written informed consent before any study-related procedure.

• Willing and able to attend all the visits scheduled in the study.

Main Exclusion Criteria:

• Patients with known concurrent temporary secondary causes of AF

• Patients that have undergone surgical or catheter ablation for AF or atrial flutter.

• Patients with an existing cardiac treatment device, pacemaker, implantable cardioverter defibrillator, or cardiac resynchronization therapy.

• Patients with a history of ECG abnormalities that, in the opinion of the investigator (or designee), render the patient unsuitable for the study.

• Patients with congestive heart failure (NYHA class III and IV).

• Patients with left atrium size = 55 mm.

• Patients with left ventricular ejection fraction = 40 %.

• Known presence of a thrombus in the left atrial appendage, left atrium, left ventricle, aorta, or intracardial mass.

• Patients with moderate or severe mitral stenosis, mitral valve rheumatic disease, unresected atrial myxoma, or a mechanical heart valve and/or other conditions, such as pulmonary embolism, considered to be formal indication for conventional anticoagulation.

• Patients with any acute coronary event, stroke, or percutaneous coronary intervention within 6 months prior to randomization or who are receiving dual antiplatelet therapy.

• Uncontrolled/therapy-resistant bradycardia and/or uncontrolled/therapy-resistant hypertension within a 3-month period prior to randomization.

• Patients having more than two DCCs in the last 6 months. Any unsuccessful pharmacological and/or electrical cardioversion (within prior 3 months).

• Patients with signs of bleeding or conditions associated with a high risk of bleeding.

• Patients taking antiarrhythmic agents within 3 days of planned randomization will be excluded.

• Patients concurrently participating in another study or unable to communicate.

• Patients with active cancer, chronic kidney disease or intercurrent illness.

• Pregnant or breastfeeding women.

• Patients taking concomitant medication.

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• OMT-28
1 capsule given daily orally from Visit 3 (Day 1) to Visit 8 (Day 99 ± 3 days).
• Placebo
1 capsule given daily orally from Visit 3 (Day 1) to Visit 8 (Day 99 ± 3 days).

Locations

Country	Name	City	State
Bulgaria	Site 401	Sofia
Bulgaria	Site 404	Stara Zagora
Bulgaria	Site 402	Varna
Czechia	Site 301	Kolín
Czechia	Site 303	Plzen
Czechia	Site 302	Slaný
Hungary	Site 201	Budapest
Hungary	Site 205	Budapest
Hungary	Site 203	Debrecen
Hungary	Site 206	Hódmezovásárhely
Hungary	Site 202	Pécs
Hungary	Site 204	Zalaegerszeg
Ukraine	Site 102	Cherkasy
Ukraine	Site 110	Ivano-Frankivs'k
Ukraine	Site 104	Kharkiv
Ukraine	Site 107	Kharkiv
Ukraine	Site 108	Khmelnytskyi
Ukraine	Site 101	Kiev
Ukraine	Site 106	Kiev
Ukraine	Site 109	Kiev
Ukraine	Site 112	Kiev
Ukraine	Site 113	Kiev
Ukraine	Site 105	Odesa
Ukraine	Site 103	Uzhgorod
Ukraine	Site 111	Zhytomyr

Sponsors (1)

Lead Sponsor	Collaborator
Omeicos Therapeutics GmbH

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Hungary,  Ukraine, 

References & Publications (2)

Fischer R, Konkel A, Mehling H, Blossey K, Gapelyuk A, Wessel N, von Schacky C, Dechend R, Muller DN, Rothe M, Luft FC, Weylandt K, Schunck WH. Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway. J Lipid Res. 2014 Jun;55(6):1150-64. doi: 10.1194/jlr.M047357. Epub 2014 Mar 16. — View Citation

Schunck WH, Konkel A, Fischer R, Weylandt KH. Therapeutic potential of omega-3 fatty acid-derived epoxyeicosanoids in cardiovascular and inflammatory diseases. Pharmacol Ther. 2018 Mar;183:177-204. doi: 10.1016/j.pharmthera.2017.10.016. Epub 2017 Nov 7. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Concentration of NT-proBNP	To assess the concentration of the exploratory, pharmacodynamic (PD) parameter NT-proBNP after once-daily administration of OMT-28 or placebo in patients with persistent AF.	Up to 3.5 months
Other	Concentration of GDF-15	To assess the concentration of the exploratory, pharmacodynamic (PD) parameter GDF-15 after once-daily administration of OMT-28 or placebo in patients with persistent AF.	Up to 3.5 months
Other	Concentration of MMP-9	To assess the concentration of the exploratory, pharmacodynamic (PD) parameter MMP-9 after once-daily administration of OMT-28 or placebo in patients with persistent AF.	Up to 3.5 months
Primary	Assessment of AF Burden After OMT-28 Administration	To assess the AF burden, based on data collected via the implantable cardiac monitor BioMonitor 2-AF, of three different doses of OMT-28 administered once daily versus placebo in the maintenance of normal sinus rhythm after electrical direct current cardioversion (DCC) in patients with persistent AF	Up to 4.5 months
Secondary	Incidence of Treatment-Emergent Adverse Events	To assess the incidence of treatment-emergent Adverse Events of three different doses of OMT-28 administered once daily versus placebo after electrical DCC in patients with persistent AF.	Up to 4.5 months
Secondary	Assessment of Pharmacokinetic (PK) Parameters of OMT-28 - AUC	To assess the pharmacokinetic (PK) parameter AUC of OMT-28 administered once daily in patients with persistent AF, by means of population PK (popPK) analysis.	Up to 3.5 months
Secondary	Assessment of Pharmacokinetic (PK) Parameters of OMT-28 - Cmax	To assess the pharmacokinetic (PK) parameter Cmax of OMT-28 administered once daily in patients with persistent AF, by means of population PK (popPK) analysis.	Up to 3.5 months

External Links

•   OMEICOS Therapeutics GmbH