Clinical trial NCT03906799: Study on OMT-28 in Maintenance of Sinus Rhythm in Patients With Persistent Atrial Fibrillation (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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atrial Fibrillation
Keywords: Atrial Fibrillation
Electrical Cardioversion
Dose-finding
Lead sponsor: Omeicos Therapeutics GmbH
Sponsor class: INDUSTRY
First posted: 2019-04-08
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of AF Burden After OMT-28 Administration
timeFrame: Up to 4.5 months
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Up to 4.5 months
measure: Assessment of Pharmacokinetic (PK) Parameters of OMT-28 - AUC
timeFrame: Up to 3.5 months
measure: Assessment of Pharmacokinetic (PK) Parameters of OMT-28 - Cmax
timeFrame: Up to 3.5 months
Other outcomes:
measure: Concentration of NT-proBNP
timeFrame: Up to 3.5 months
measure: Concentration of GDF-15
timeFrame: Up to 3.5 months
measure: Concentration of MMP-9
timeFrame: Up to 3.5 months
Locations:
city: Sofia
country: Bulgaria
facility: Site 401
city: Stara Zagora
country: Bulgaria
facility: Site 404
city: Varna
country: Bulgaria
facility: Site 402
city: Kolín
country: Czechia
facility: Site 301
city: Plzen
country: Czechia
facility: Site 303
city: Slaný
country: Czechia
facility: Site 302
city: Budapest
country: Hungary
facility: Site 205
city: Budapest
country: Hungary
facility: Site 201
city: Debrecen
country: Hungary
facility: Site 203
city: Hódmezővásárhely
country: Hungary
facility: Site 206
city: Pécs
country: Hungary
facility: Site 202
city: Zalaegerszeg
country: Hungary
facility: Site 204
city: Cherkasy
country: Ukraine
facility: Site 102
city: Ivano-Frankivs'k
country: Ukraine
facility: Site 110
city: Kharkiv
country: Ukraine
facility: Site 104
city: Kharkiv
country: Ukraine
facility: Site 107
city: Khmelnytskyi
country: Ukraine
facility: Site 108
city: Kiev
country: Ukraine
facility: Site 113
city: Kiev
country: Ukraine
facility: Site 106
city: Kiev
country: Ukraine
facility: Site 101
city: Kiev
country: Ukraine
facility: Site 109
city: Kiev
country: Ukraine
facility: Site 112
city: Odesa
country: Ukraine
facility: Site 105
city: Uzhgorod
country: Ukraine
facility: Site 103
city: Zhytomyr
country: Ukraine
facility: Site 111
Study officials:
affiliation: Managing Director
name: Alexander Gebauer, Dr.med.
role: STUDY_DIRECTOR
References:
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.
citation: 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.