Clinical Randomised Phase 2 Trial of AP31969 Versus Placebo for Rhythm Control of Atrial Fibrillation (END-AF-1)

A clinical Randomized Phase 2 Trial of AP31969 versus Placebo for Rhythm Control of Atrial Fibrillation.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation (AF)
• Intervention / Treatment: Drug: AP31969; Drug: Placebo

Detailed Description

The key goal of this clinical trial is to assess the effectiveness of different doses of AP31969 in lowering Atrial Fibrillation (AF) burden and its safety.

Participants will be randomly assigned to one of the following groups:

• AP31969 at 100 mg, 200 mg, or 350 mg doses
• AP31969 500 mg (not included at the trial start)
• Placebo (inactive treatment and has no active properties). The placebo group serves as the comparator for AP31969. All treatments are given orally, twice daily.

The trial includes 3 periods: screening (up to 4 weeks), treatment (12 weeks), and follow-up (30 days). The duration of the trial for a participant is approximately 20 weeks.

Participants will receive an implantable loop recorder and undergo assessments during the visits at specific times, for example blood and urine analyses, and electrocardiogram.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Birgitte Vestbjerg; Phone Number: +0045 2077 2575; Email: bve@acesionpharma.com

Study Locations

• Bulgaria
  • PD
    • Plovdiv, PD, Bulgaria, 4002
      • Not yet recruiting
      • UMHAT "Sveti Georgi" EAD, Department of Invasive Cardiology
  • SOF
    • Sofia, SOF, Bulgaria, 1000
      • Recruiting
      • Acibadem City Clinic, Cardiology Department
    • Sofia, SOF, Bulgaria, 1365
      • Withdrawn
      • MHAT National Cardiology Hospital EAD, Cardiology Department
    • Sofia, SOF, Bulgaria, 1431
      • Not yet recruiting
      • Aleksandrovska University Hospital, Clinic of Cardiology
  • VAR
    • Varna, VAR, Bulgaria, 9000
      • Recruiting
      • SHATC Cardiolife, Invasive Cardiology
    • Varna, VAR, Bulgaria, 9020
      • Recruiting
      • Medical Center Nova Clinic
• Denmark
  • Hellerup, Denmark, 2730
    • Recruiting
    • University Hospital Herlev and Gentofte Department of Cardiology
  • Viborg, Denmark, 8800
    • Recruiting
    • Viborg Hospital, Department of Cardiology
• Germany
  • Coburg, Germany, 96450
    • Not yet recruiting
    • Sana Kliniken Oberfranken, Klinikum Coburg Kardiologie und Innere Medizin
  • Frankfurt, Germany, 60590
    • Recruiting
    • Universitätsklinikum Frankfurt Medizinische Klinik III - Kardiologie, Angiologie, Hämostaseologie, Nephrologie
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitaets Klinikum Hamburg-Eppendorf (UKE Hamburg), Kardiologie
• Hungary
  • Budapest, Hungary, 1023
    • Not yet recruiting
    • Budai Irgalmasrendi Korhaz
  • Budapest, Hungary, 1122
    • Recruiting
    • Semmelweis Egyetem Városmajori Sziv- és Érsebészeti Klinika
  • Sopron, Hungary, 9400
    • Not yet recruiting
    • Soproni Gyógyközpont Soproni Erzsébet Oktató Kórház és Rehabilitációs Intézet
  • Szeged, Hungary, 6725
    • Not yet recruiting
    • Szent-Györgyi Albert Klinikai Központ, Belgyógyászati Klinika
  • Szolnok, Hungary, 5000
    • Not yet recruiting
    • Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet
  • Zalaegerszeg, Hungary, 8900
    • Not yet recruiting
    • Belvárosi Egészségház, Platán Magánklinika
• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Not yet recruiting
      • Policlinico Sant'Orsola Cardiology Department
  • FE
    • Cona, FE, Italy, 444124
      • Not yet recruiting
      • Arcispedale Sant'Anna, Cardiology Department
  • Michigan
    • Milan, Michigan, Italy, 20162
      • Not yet recruiting
      • ASST Grande Ospedale Metropolitano Niguarda Cardiology 3 - Electrophysiology "De Gasperis" Cardio Center
  • Missouri
    • Modena, Missouri, Italy, 30174
      • Not yet recruiting
      • University of Modena and Reggio Emilia, Policlinico di Modena, Cardiology Department
  • VE
    • Mestre, VE, Italy, 30174
      • Not yet recruiting
      • Dell'Angelo Hospital, Cardiology Department
• Netherlands
  • Arnhem, Netherlands, 6815 AD
    • Recruiting
    • Rijnstate Ziekenhuis, Cardiology Department
  • Deventer, Netherlands, 7416 SE
    • Recruiting
    • Deventer Ziekenhuis, Cardiology Department
  • Groningen, Netherlands, 9728 NT
    • Recruiting
    • Martini Hospital Groningen, Cardiology Department
  • Haarlem, Netherlands, 2035 RC
    • Recruiting
    • Spaarne Gasthuis, Cardiology Department
  • Leeuwarden, Netherlands, 8934 AD
    • Recruiting
    • Frisius MC Leeuwarden, Hart- en Vaatcentrum
  • Maastricht, Netherlands, 6229 HX
    • Not yet recruiting
    • Maastricht University Medical Center, Cardiology Department
  • The Hague, Netherlands, 2545 AA
    • Not yet recruiting
    • HagaZiekenhuis, Cardiology/Electrophysiology Unit
  • Tiel, Netherlands, 4002 WP
    • Recruiting
    • Rivierenland Hospital, Cardiology Department
  • Veldhoven, Netherlands, 5504 DB
    • Recruiting
    • Máxima Medisch Centrum, Cardiology Department
• Poland
  • Bydgoszcz, Poland, 85-231
    • Not yet recruiting
    • Centrum Medyczne KERmed Cardiology Department
  • Chrzanów, Poland, 85-231
    • Not yet recruiting
    • Małopolskie Centrum Sercowo-Naczyniowe PAKS Oddział Intensywnej Opieki Kardiologicznej
  • Dąbrowa Górnicza, Poland, 41-300
    • Recruiting
    • Polsko-Amerykańskie Kliniki Serca III Oddział Kardiologii Inwazyjnej, Angiologii i Elektrokardiologii
  • Katowice, Poland, 40-635
    • Not yet recruiting
    • Górnoslaskie Centrum Medyczne im. prof. Leszka Gieca Slaskiego Uniwersytetu Medycznego w Katowicach
  • Katowice, Poland, 40-635
    • Not yet recruiting
    • Upper-Silesian Medical Center 2nd Department of Cardiology
  • Szczecin, Poland, 70-419
    • Not yet recruiting
    • One Day Med Sp. z o.o. Clinical Trials Department
  • Tychy, Poland, 43-100
    • Recruiting
    • Polsko-Amerykańskie Kliniki Serca X Oddział Kardiologii Inwazyjnej, Elektrofizjologii i Elektrostymulacji w Tychach im

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Willing and able to provide written informed consent.
• Age 18 or older.
• ECG documented diagnosis of paroxysmal or persistent AF.
• AF history at screening indicating an expected AF burden of 1-90%, i.e., at least 1 self-terminating AF episode within 4 months prior to the screening visit.
• AF burden of ≥ 1% and ≤ 90% assessed with an ECG patch device during the screening period prior to the randomisation visit.

• Investigator and participant agreement to avoid non-trial related rhythm control intervention for the duration of the trial, including:

  • Antiarrhythmic drug class I and/or III (including amiodarone)
  • Electrical or pharmacological cardioversion
  • AF ablation procedure
• Willing to have a loop recorder implanted.

Exclusion Criteria:

• Prior AF ablation procedure other than pulmonary vein isolation (PVI) only.
• Any of the following events within 4 weeks prior to the screening visit: Myocardial infarction, Unstable angina pectoris, Stroke or transient, ischaemic attack, Percutaneous coronary intervention (PCI), Coronary artery bypass graft (CABG), Peripheral revascularisation procedure.
• Cardiac pacing device e.g. pacemaker and cardiac resynchronization therapy device with atrial or ventricular pacing for > 5% of the time or existing implantable loop recorder.
• Heart failure, New York Heart Association class III (3) or IV (4).
• Left ventricular ejection fraction < 40% based on imaging (e.g. echocardiography) performed within 6 months prior to or during the screening visit.
• Clinically significant valvular heart disease, including severe aortic stenosis, severe mitral regurgitation and/or severe mitral stenosis, in the opinion of the investigator.
• QTc (Fridericia, QTcF) interval > 450 ms for males and > 470 ms for females at screening.
• eGFR <60 mL/min /1.73 m² based on creatine and CKD-EPI formula
• Use of antiarrhythmic drug class I and/or III within 7 days or, for amiodarone, within 3 months prior to the screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AP31969 100 mg; Tablets, Twice daily, 12 Weeks	Drug: AP31969; Tablets, Oral, Twice daily.
Experimental: AP31969 200 mg; Tablets, Twice daily, 12 Weeks	Drug: AP31969; Tablets, Oral, Twice daily.
Experimental: AP31969 350 mg; Tablets, Twice daily, 12 Weeks	Drug: AP31969; Tablets, Oral, Twice daily.
Experimental: AP31969 500 mg; Tablets, Twice daily, 12 Weeks	Drug: AP31969; Tablets, Oral, Twice daily.
Placebo Comparator: Placebo; Tablets, Twice daily, 12 Weeks	Drug: Placebo; Tablets, oral, Twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atrial fibrillation burden	Measured through implantable loop recorder. Calculated as the amount of time with AF relative to the amount of time the participant is under observation (expressed as a %).	From week 2 to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of atrial fibrillation episodes	Measured through implantable loop recorder.	From week 2 to week 12
Change from baseline in Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT)	Patient reported outcome.	Week 12
Number of ventricular tachycardia episodes > 30 seconds of duration	Measured through implantable loop recorder.	From week 0 to week 12

Collaborators and Investigators

• Sponsor: Acesion Pharma

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 25, 2025
• First Submitted That Met QC Criteria: November 25, 2025
• First Posted (Actual): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; AP31969; SK channel inhibitor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation
• Other Study ID Numbers: AP31969-M201; 2025-521377-14-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request access to anonymized data and needed trial documentation. Requests are evaluated on the basis of scientific merit. Any use of and access to the data must respect the privacy of the participants and will only be provided if applicable laws and regulations allow this.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No