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

Novartis

Status and phase: Enrolling; Phase 2

Conditions: Atrial Fibrillation

Treatments: Drug: PKN605; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07217067

CPKN605A12201

Details and patient eligibility

About

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

Full 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.

Enrollment: 165 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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
  • 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 within the last 6 months 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
• Current decompensated heart failure or hospitalization for heart failure within 3 months prior to Screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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165 participants in 3 patient groups, including a placebo group

PKN605 lower dose

Experimental group

Description:

PKN605 is an oral fomulation

Treatment:

Drug: PKN605

PKN605 higher dose

Experimental group

Description:

PKN605 is an oral formulation

Treatment:

Drug: PKN605

Placebo

Placebo Comparator group

Description:

Placebo is an oral formulation

Treatment:

Other: Placebo