A study to investigate the efficacy, safety, tolerability and pharmacokinetics of PKN605 in participants with atrial fibrillation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

6 Jan 2026 → ongoing

Decision date (initial)

2025-11-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2025-520518-79-00

WHO UTN

U1111-1325-4513

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Others, Efficacy

To evaluate the effect of PKN605 on atrial fibrillation burden

Secondary objectives 3

1. To evaluate the effect of PKN605 on AF recurrence
2. To evaluate the safety and tolerability of PKN605 in participants with AF
3. To evaluate the pharmacokinetics of PKN605 in participants with AF

Conditions and MedDRA coding

Atrial Fibrillation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Signed informed consent must be obtained prior to participation in the study
2. Male and female participants > 18 years of age
3. History of at least 2 episodes of AF (atrial fibrillation or atrial flutter), at least one episode must be atrial fibrilation
4. At least one 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
5. One or more of the following, at Screening: • 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, 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
6. On guideline-directed stroke prevention treatment, as confirmed by the investigator, at Screening
7. Participants must have a body mass index (BMI) >18 kg/m2. BMI is calculated as body weight (kg) divided by height in (m) squared
8. Sinus rhythm at Baseline as documented by a 12-lead ECG (participants with persistent AF should be cardioverted at least 12 hours before randomization)

Exclusion criteria 8

1. Permanent AF
2. Ongoing reversible causes of AF (e.g., hyperthyroidism, myocarditis, alcohol use, sepsis- or infection-related AF, surgery-related AF, pulmonary embolism)
3. Ongoing use of antiarrhythmic therapy (Vaughan Williams class l 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)
4. History of an AF ablation procedure without a recurrence of AF at least 2 or more months after the ablation
5. Implanted pacemaker, defibrillator, or cardiac monitor
6. Infiltrative (e.g., amyloidosis, sarcoidosis) or hypertrophic cardiomyopathy
7. Current decompensated heart failure or hospitalization for heart failure within 3 months prior to Screening
8. Left ventricular ejection fraction of 40% or less documented within the last 12 months, or during the Screening period. If multiple LVEF measurements are recorded within last 12 months, the most recent LVEF measurement should be used.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AFB from ECG patch monitors, defined as the amount of time spent in AF as a proportion of the analyzable monitoring time

Secondary endpoints 3

1. Time (d) from the date of randomization to first AF recurrence and presence (or absence) of AF recurrence after randomization detected by ECG patch monitor, 12-lead ECG, handheld ECG, or other protocol-approved method for ascertainment
2. Adverse events, vital signs, 12-lead ECG parameters (including QTcF), and laboratory assessments
3. PKN605 plasma concentrations; Ctrough (pre-dose), C2h, C4h

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 11

Locations

2 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications