Clinical Phase 2 Trial of AP31969 Versus Placebo for Rhythm Control of Atrial Fibrillation

Official title

Clinical Randomised Phase 2 Trial of AP31969 Versus Placebo for Rhythm Control of Atrial Fibrillation

Overview

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

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.

Interventions

• Drug AP31969
  Tablets, Oral, Twice daily.
• Drug Placebo
  Tablets, oral, Twice daily.

Primary outcome measures

• Atrial fibrillation burden [Time frame: From week 2 to week 12]

Secondary outcome measures (3)

• Number of atrial fibrillation episodes [Time frame: From week 2 to week 12]
• Change from baseline in Atrial Fibrillation Effect on Quality-of-Life [Time frame: Week 12]
• Number of ventricular tachycardia episodes > 30 seconds of duration [Time frame: From week 0 to week 12]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Netherlands · 9 centers

• Rijnstate Ziekenhuis, Cardiology Department — Arnhem
• Deventer Ziekenhuis, Cardiology Department — Deventer
• Martini Hospital Groningen, Cardiology Department — Groningen
• Spaarne Gasthuis, Cardiology Department — Haarlem
• Frisius MC Leeuwarden, Hart- en Vaatcentrum — Leeuwarden
• Maastricht University Medical Center, Cardiology Department — Maastricht
• HagaZiekenhuis, Cardiology/Electrophysiology Unit — The Hague
• Rivierenland Hospital, Cardiology Department — Tiel
• … and 1 more center

Poland · 7 centers

• Centrum Medyczne KERmed Cardiology Department — Bydgoszcz
• Małopolskie Centrum Sercowo-Naczyniowe PAKS Oddział Intensywnej Opieki Kardiologicznej — Chrzanów
• Polsko-Amerykańskie Kliniki Serca III Oddział Kardiologii Inwazyjnej, Angiologii i Elektro — Dąbrowa Górnicza
• Gornoslaskie Centrum Medyczne im. prof. Leszka Gieca Slaskiego Uniwersytetu Medycznego w K — Katowice
• Upper-Silesian Medical Center 2nd Department of Cardiology — Katowice
• One Day Med Sp. z o.o. Clinical Trials Department — Szczecin
• Polsko-Amerykańskie Kliniki Serca X Oddział Kardiologii Inwazyjnej, Elektrofizjologii i El — Tychy

Bulgaria · 6 centers

• UMHAT "Sveti Georgi" EAD, Department of Invasive Cardiology — Plovdiv
• Acibadem City Clinic, Cardiology Department — Sofia
• MHAT National Cardiology Hospital EAD, Cardiology Department — Sofia
• Aleksandrovska University Hospital, Clinic of Cardiology — Sofia
• SHATC Cardiolife, Invasive Cardiology — Varna
• Medical Center Nova Clinic — Varna

Hungary · 6 centers

• Budai Irgalmasrendi Kórház — Budapest
• Semmelweis Egyetem Városmajori Sziv- és Érsebészeti Klinika — Budapest
• Soproni Gyógyközpont Soproni Erzsébet Oktató Kórház és Rehabilitációs Intézet — Sopron
• Szent-Györgyi Albert Klinikai Központ, Belgyógyászati Klinika — Szeged
• Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház-Rendelőintézet — Szolnok
• Belvárosi Egészségház, Platán Magánklinika — Zalaegerszeg

Serbia · 6 centers

• Institute for Cardiovascular Disease "Dedinje" Department for Electrophysiology — Belgrade
• University Clinical Centre of Serbia Department for Intensive Care in Arrhythmology — Belgrade
• Institute for Cardiovascular Diseases Vojvodina Department of Interventional Electrophysio — Kamenitz
• University Clinical Center Kragujevac Clinic of Cardiology (Depar. Electrophysiology) — Kragujevac
• University Clinical Center Nis Clinic for Cardiovascular Diseases Bulevar — Niš
• Health Center Uzice Cardiology Department — Užice

Italy · 5 centers

• Policlinico Sant'Orsola Cardiology Department — Bologna
• Arcispedale Sant'Anna, Cardiology Department — Cona
• Dell'Angelo Hospital, Cardiology Department — Mestre
• ASST Grande Ospedale Metropolitano Niguarda Cardiology 3 - Electrophysiology "De Gasperis" — Milan
• University of Modena and Reggio Emilia, Policlinico di Modena, Cardiology Department — Modena

Germany · 3 centers

• Sana Kliniken Oberfranken, Klinikum Coburg Kardiologie und Innere Medizin — Coburg
• Universitätsklinikum Frankfurt Medizinische Klinik III - Kardiologie, Angiologie, Hämostas — Frankfurt
• Universitaets Klinikum Hamburg-Eppendorf (UKE Hamburg), Kardiologie — Hamburg

Denmark · 2 centers

• University Hospital Herlev and Gentofte Department of Cardiology — Hellerup
• Viborg Hospital, Department of Cardiology — Viborg

Identifiers

NCT: NCT07267949 · AP31969-M201 · 2025-521377-14-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗