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)

Study Overview
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Brief Summary
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A study to evaluate the effect of abelacimab relative to placebo on the rate of ischemic stroke or systemic embolism (SE) in patients with Atrial Fibrillation (AF) who have been deemed by their responsible physicians or by their own decision to be unsuitable for oral anticoagulation therapy.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group 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)

Conditions
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Atrial Fibrillation (AF)

Intervention / Treatment
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* Biological: Abelacimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is able to understand and willing to provide 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 ≥5 OR age ≥75 and a CHA2DS2VASc ≥4 Judged by the responsible physician or by their own decision to be unsuitable for oral anticoagulation 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 Exclusion Criteria: AF due to an ongoing acute reversible cause (e.g., cardiac surgery, pulmonary embolism (PE), untreated hyperthyroidism, alcohol use) Patients who received warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban within 60 days prior to randomization 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 Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abelacimab (MAA868)<br>Patients will be randomized in a 1:1 ratio to receive abelacimab 150 mg subcutaneous (SC) or matching placebo once monthly. | Biological: Abelacimab<br>* Abelacimab provided as liquid in vial (150 mg/mL)<br>* Other names: MAA868;|
| Placebo Comparator: Placebo<br>Patients will be randomized in a 1:1 ratio to receive abelacimab 150 mg subcutaneous (SC) or matching placebo once monthly. | Drug: Placebo<br>* Dosage Formulation: Liquid (in vial) Dose Strength: Placebo to Abelacimab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Time to first event of ischemic stroke or systemic embolism (SE) |  | Up to 30 months | 
| Safety: Time to first occurrence of Bleeding Academic Research Consortium (BARC) type 3c/5 bleeding |  | Up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Time to first event of ischemic stroke, systemic embolism (SE), myocardial infarctions (MI), venous thromboembolism (VTE), or acute limb ischemia | Abelacimab versus placebo with regard to the composite of ischemic stroke, SE, MI, VTE, or acute limb ischemia | Up to 30 months | 
| Efficacy: Time to first event of ischemic stroke, systemic embolism (SE), or Bleeding Academic Research Consortium (BARC) type 3c/5 bleeding event |  | Up to 30 months | 
| Efficacy: Cardiovascular (CV) mortality |  | Up to 30 months | 
| Efficacy: All-cause mortality |  | Up to 30 months | 
| Time to first event of ischemic stroke, systemic embolism (SE), myocardial infarctions (MI), venous thromboembolism (VTE), acute limb ischemia, or International Society on Thrombosis and Haemostasis (ISTH) major bleeding | Abelacimab versus placebo with regard to net clinical outcome defined as the composite of ischemic stroke, SE, MI, VTE, acute limb ischemia, or International Society on Thrombosis and Haemostasis (ISTH) major bleeding | Up to 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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abelacimab, randomized, placebo-controlled, double-blind, endpoint evaluation, atrial fibrillation