Study to evaLuate the effIcacy and Safety of abeLacimab in High-risk Patients With Atrial Fibrillation Who Have Been Deemed Unsuitable for Oral antiCoagulation (LILAC-TIMI 76)

Patients enrolled in the study are randomized in a 1:1 ratio to receive abelacimab 150 mg SC or matching placebo once monthly. The study is comprised of 3 periods: 1) screening period of up to 60 days, 2) an event-driven, double-blind treatment period (abelacimab 150 mg SC or matching placebo) completed after at least 111 patients have experienced an adjudicated primary endpoint event, and 3) EoT visit in core part followed by either (i) a 30-day follow-up period (EoS for core part) OR (ii) an optional OLE beginning at the EoT visit for eligible patients to receive open-label abelacimab treatment. The optional extension will only be offered to patients following regulatory and ethics approval in participating countries.

Inclusion criteria

• Patient is able to understand and has provided written informed consent to participate in the trial
• Diagnosed Atrial Fibrillation (AF) or atrial flutter (documented on an electrocardiogram (ECG) or monitor recording)
• Age 65-74 and a CHA2DS2VASc ≥4 OR age ≥75 and a CHA2DS2VASc ≥3
• Patient is judged by the responsible physician to be unsuitable for oral anticoagulation because the risks outweigh the benefits or the patient is unwilling to take oral anticoagulation AND this determination was made prior to and independent of the study
• At least 1 bleeding risk factor such as severe renal insufficiency, planned daily use of antiplatelet medication for the duration of the trial, history of bleeding from a critical area, or other conditions associated with increased risk of bleeding such as chronic nonsteroidal anti-inflammatory drug (NSAID) use, frailty or multiple falls
• Patient is judged by the responsible physician to be unsuitable for left atrial appendage (LAA) closure or occlusion device, an approved device is not available, or the patient is unwilling to undergo the procedure AND this determination was made prior to and independent of the study

Exclusion criteria

• AF due to an ongoing acute reversible cause (e.g., cardiac surgery, pulmonary embolism (PE), untreated hyperthyroidism, alcohol use)
• Patients who within 60 days prior to randomization (1) received a vitamin K antagonists (VKA) (e.g., warfarin, phenprocoumon, acenocoumarol) or a direct oral anticoagulant (DOAC) such as, dabigatran, rivaroxaban, apixaban, or edoxaban or (2) were newly diagnosed with AF
• Patients with an intracranial or intraocular bleed within the 3 months prior to screening or any history of spontaneous intracerebral hemorrhage at any time in the absence of antithrombotic treatment
• Any stroke within 14 days before randomization or transient ischemic attack (TIA) within 3 days before randomization
• Mechanical heart valve or valve disease that is expected to require mechanical valve replacement intervention (surgical or invasive) during the course of the study
• Patients on dialysis at screening or who are planned to start dialysis within 6 months

Other protocol defined Inclusion/Exclusion criteria may apply