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

Phase 2

Completed

• Conditions: Atrial Fibrillation
• Interventions: Drug: OMT-28; Drug: Placebo

• Registration Number: NCT03906799
• Lead Sponsor: Omeicos Therapeutics GmbH

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.

Study Timeline

• Status Verified: 2019-03
• Study Start: 2019-03-19
• Study First Submitted: 2019-03-20
• Study First Submitted QC: 2019-04-05
• Study First Posted: 2019-04-08
• Primary Completion: 2019-11-20
• Study Completion: 2020-03-20
• Last Update Submitted: 2021-09-08
• Last Update Posted: 2021-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 136

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High OMT-28	OMT-28	Verum, high OMT-28
Placebo	Placebo	Placebo
Middle OMT-28	OMT-28	Verum, middle OMT-28
Low OMT-28	OMT-28	Verum, low OMT-28

Primary Outcome Measures

Name	Time	Method
Assessment of AF Burden After OMT-28 Administration	Up to 4.5 months	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

Secondary Outcome Measures

Name	Time	Method
Assessment of Pharmacokinetic (PK) Parameters of OMT-28 - Cmax	Up to 3.5 months	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.
Incidence of Treatment-Emergent Adverse Events	Up to 4.5 months	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.
Assessment of Pharmacokinetic (PK) Parameters of OMT-28 - AUC	Up to 3.5 months	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.

Trial Locations

Locations (25)

Site 106; 🇺🇦 Kiev, Ukraine

Site 101; 🇺🇦 Kiev, Ukraine

Site 109; 🇺🇦 Kiev, Ukraine

Site 401; 🇧🇬 Sofia, Bulgaria

Site 404; 🇧🇬 Stara Zagora, Bulgaria

Site 104; 🇺🇦 Kharkiv, Ukraine

Site 205; 🇭🇺 Budapest, Hungary

Site 202; 🇭🇺 Pécs, Hungary

Site 111; 🇺🇦 Zhytomyr, Ukraine

Site 303; 🇨🇿 Plzen, Czechia

Site 302; 🇨🇿 Slaný, Czechia

Site 107; 🇺🇦 Kharkiv, Ukraine

Site 102; 🇺🇦 Cherkasy, Ukraine

Site 110; 🇺🇦 Ivano-Frankivs'k, Ukraine

Site 108; 🇺🇦 Khmelnytskyi, Ukraine

Site 201; 🇭🇺 Budapest, Hungary

Site 402; 🇧🇬 Varna, Bulgaria

Site 301; 🇨🇿 Kolín, Czechia

Site 203; 🇭🇺 Debrecen, Hungary

Site 206; 🇭🇺 Hódmezővásárhely, Hungary

Site 204; 🇭🇺 Zalaegerszeg, Hungary

Site 113; 🇺🇦 Kiev, Ukraine

Site 112; 🇺🇦 Kiev, Ukraine

Site 103; 🇺🇦 Uzhgorod, Ukraine

Site 105; 🇺🇦 Odesa, Ukraine