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

OMEICOS Therapeutics

Status and phase: Completed; Phase 2

Conditions: Atrial Fibrillation

Treatments: Drug: Placebo; Drug: OMT-28

Study type: Interventional

Funder types: Industry

Identifiers

NCT03906799

OMT28-C0201

Details and patient eligibility

About

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.

Full 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.

Enrollment: 136 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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136 participants in 4 patient groups, including a placebo group

Low OMT-28

Experimental group

Description:

Verum, low OMT-28

Treatment:

Drug: OMT-28

Middle OMT-28

Experimental group

Description:

Verum, middle OMT-28

Treatment:

Drug: OMT-28

High OMT-28

Experimental group

Description:

Verum, high OMT-28

Treatment:

Drug: OMT-28

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo