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NCT07217067PHASE2Recruiting

A Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of PKN605 in Participants With Atrial Fibrillation

Novartis Pharmaceuticals

Start Date

10/28/2025

Completion Date

9/9/2027

Summary

A randomized, placebo-controlled, participant-and investigator-blinded study to evaluate the efficacy in reducing atrial fibrillation burden as well as the safety, tolerability and pharmacokinetics of PKN605 in participants with atrial fibrillation

Detailed Description

A screening period of up to 90 days will be conducted to determine participants' eligibility. Once eligibility is confirmed, participants will be randomly assigned to receive either PKN605 or placebo. The treatment phase will last for 24 weeks, during which participants will visit the clinic approximately once a month. During the study, participants' atrial fibrillation will be monitored using various ECG devices. Approximately one month after the end of the treatment phase, participants will have a final safety follow-up visit. The primary purpose of the study is to monitor the effect PKN605 has on the amount of time participants spend in atrial fibrillation.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Inclusions at Screening * Signed informed consent must be obtained prior to participation in the study * Male and female participants ≥ 18 years of age * History of at least 2 episodes of AF (atrial fibrillation or atrial flutter), at least one episode must be atrial fibrillation * At least 1 of the AF episodes specified in inclusion #3 must be within the last 12 months (or during screening) and documented by 12-lead ECG, Holter, or any other ECG recording method, as confirmed by the Investigator * One or more of the following: * AFB of 1% or higher on a local ambulatory Holter, mobile cardiac telemetry, ECG patch monitor, or other ambulatory electrocardiographic monitor within the last 12 months * CHA2DS2-VASc score of 2 or higher in males, 3 or higher in females (1 point for congestive heart failure, hypertension, age 65-74 years, diabetes, vascular disease, female sex; 2 points for age 75 years or older, prior stroke or transient ischemic attack) * Stable heart failure or with New York Heart Association class I or II symptoms * NT-proBNP level of 300 pg/mL or higher on a local lab test within the last 12 months * On guideline-directed stroke prevention treatment, as confirmed by the Investigator * Participants must have a body mass index (BMI) ≥ 18 kg/m2. BMI is calculated as body weight (kg) divided by height (m) squared * Inclusions at Day 1 * Sinus rhythm at Baseline documented by 12-lead ECG (participants with persistent AF should be cardioverted at least 12 hours before randomization) Exclusion Criteria: -Exclusions at Screening * Permanent AF * Ongoing reversible causes of AF (e.g., hyperthyroidism, myocarditis, acute alcohol, sepsis- or infection related AF, surgery-related AF, pulmonary embolism) * Ongoing use of antiarrhythmic therapy (Vaughan Williams class I or III anti-arrhythmic therapy must be discontinued at least 7 days before Screening phase ECG patch monitor; amiodarone must be discontinued at least 6 weeks before Screening phase ECG patch monitor) * History of an AF ablation procedure without a recurrence of AF at least 2 or more months after the ablation. * Implanted pacemaker, defibrillator, or cardiac monitor * Infiltrative (e.g., amyloidosis, sarcoidosis) or hypertrophic cardiomyopathy * Left ventricular ejection fraction of 40% or less documented within the last 12 months, or during Screening. If multiple LVEF measurements are recorded within the last 12 months, the most recent LVEF measurement should be used * Current decompensated heart failure or hospitalization for heart failure within 3 months prior to Screening

Interventions

DRUG

PKN605

OTHER

Placebo

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Conditions

Atrial Fibrillation

Locations

Cardiology Associates of North MS

Tupelo, Mississippi 38801

United States

Cooper University Hospital

Camden, New Jersey 08103

United States

Weill Cornell Medical Center

New York, New York 10021

United States

Duke Univ Medical Center

Durham, North Carolina 27710

United States

Intermountain Medical Center

Murray, Utah 84107

United States

Swedish Heart and Vascular Clinic

Seattle, Washington 98122

United States

Novartis Investigative Site

Calgary, Alberta T2P 3C5

Canada

Novartis Investigative Site

Vancouver, British Columbia V5Z 1M9

Canada

Novartis Investigative Site

Halifax, Nova Scotia B3H 3A7

Canada

Novartis Investigative Site

Hamilton, Ontario L8L 2X2

Canada

Novartis Investigative Site

London, Ontario N6A 5W9

Canada

Novartis Investigative Site

Newmarket, Ontario L3Y 2P6

Canada

Novartis Investigative Site

Toronto, Ontario M4N 3M5

Canada

Novartis Investigative Site

Toronto, Ontario M5B 1W8

Canada

Novartis Investigative Site

Montreal, Quebec H1T 1C8

Canada

Novartis Investigative Site

Montreal, Quebec H2X 1R9

Canada

Novartis Investigative Site

Montreal, Quebec H4A 3J1

Canada

Novartis Investigative Site

Québec, Quebec G1V 4G5

Canada

Novartis Investigative Site

Sherbrooke, Quebec J1H 5N4

Canada

Novartis Investigative Site

Beijing, Beijing Municipality 100013

China

Novartis Investigative Site

Beijing, 100730

China

Novartis Investigative Site

Xi'an, 223001

China

Novartis Investigative Site

Bad Homburg, 61348

Germany

Novartis Investigative Site

Berlin, 10787

Germany

Novartis Investigative Site

Berlin, 13353

Germany

Novartis Investigative Site

Hamburg, 20099

Germany

Novartis Investigative Site

Hamburg, 20246

Germany

Novartis Investigative Site

Arnhem, Gelderland 6815 AD

Netherlands

Novartis Investigative Site

Maastricht, Limburg 6229 HX

Netherlands

Novartis Investigative Site

Delft, South Holland 2625 AD

Netherlands

Novartis Investigative Site

Goes, Zeeland 4462 RA

Netherlands

Novartis Investigative Site

Groningen, 9713 GZ

Netherlands

Novartis Investigative Site

Veldhoven, 5504 DB

Netherlands

Novartis Investigative Site

Singapore, Singapore S308433

Singapore

Novartis Investigative Site

Singapore, 119074

Singapore

Novartis Investigative Site

Singapore, 169609

Singapore

Novartis Investigative Site

Brighton, East Sussex BN2 5BE

United Kingdom

Novartis Investigative Site

Newcastle upon Tyne, Tyne and Wear NE7 7DN

United Kingdom

Novartis Investigative Site

Liverpool, L14 3PE

United Kingdom

Novartis Investigative Site

London, W12 0HS

United Kingdom