A Study of Milvexian Versus Apixaban in Participants With Atrial Fibrillation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate if milvexian is at least as effective as apixaban for reducing the risk of the composite stroke and non- central nervous system (CNS) systemic embolism.

Official Title
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A Phase 3, Randomized, Double-Blind, Double-Dummy, Parallel Group, Active-Controlled Study to Evaluate the Efficacy and Safety of Milvexian, an Oral Factor XIa Inhibitor, Versus Apixaban in Participants With Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Milvexian
* Drug: Apixaban
* Drug: Placebo
* Drug: Apixaban Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Minimum age of 18 years Medically stable and appropriate for chronic antithrombotic treatment Atrial fibrillation eligible to receive anticoagulation Participant must satisfy one or both of the following categories of risk factors (a or b): a) one or more of the following risk factors: i) age greater than or equal to 75 years, ii) history of a clinical symptomatic stroke. b) two or more of the following risk factors: i) age between 65 and 74 years, ii) hypertension, iii) diabetes mellitus, iv) atherosclerotic vascular disease, v) heart failure Exclusion Criteria: Hemodynamically significant valve disease or those with valve disease that will potentially require surgical valve replacement during the study Any condition other than AF that requires chronic anticoagulation

Ages Eligible for Study
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Minimum Age: 18 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: Milvexian<br>Participants will receive milvexian 100 milligrams (mg) orally, twice daily and placebo that matches apixaban beginning on Day 1 through end of treatment (EOT). Participants after the EOT visit may have an option to receive open-label apixaban at the appropriate dose (5 mg or 2.5 mg, twice daily), for which the sponsor provides a 30-day supply. | Drug: Milvexian<br>* Milvexian will be administered orally.<br>Drug: Placebo<br>* Milvexian matching milvexian placebo will be administered orally.<br>|
| Active Comparator: Apixaban<br>Participants will receive a placebo that matches milvexian and a capsule containing apixaban 5 mg or 2.5 mg orally, twice daily. Participants after the EOT visit may have an option to receive open-label apixaban (5 mg or 2.5 mg, twice daily) at the appropriate dose, for which the sponsor provides a 30-day supply. | Drug: Apixaban<br>* Apixaban will be administered orally.<br>Drug: Apixaban Placebo<br>* Apixaban matching apixaban placebo will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the First Occurrence of Composite Endpoint of Stroke and Non-central nervous system (CNS) Systemic Embolism | Time to the first occurrence of composite endpoint of stroke and non-CNS systemic embolism will be reported. | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the First Occurrence of International Society of Thrombosis and Hemostasis (ISTH) Major Bleeding | Time to the first occurrence of ISTH major bleeding will be reported. | Up to 4 years | 
| Time to the First Occurrence of the Composite of ISTH Major and Clinically Relevant Non-major (CRNM) Bleeding | Time to the first occurrence of the composite of ISTH major and CRNM bleeding will be reported. | Up to 4 years | 
| Time to the First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, and Non-CNS Systemic Embolism | Time to the first occurrence of composite endpoint of CV death, MI, stroke, and non-CNS systemic embolism will be reported. | Up to 4 years | 
| Time to CV Death | Time to CV death will be reported. | Up to 4 years | 
| Time to the First Occurrence of Composite Endpoint of All-cause Death, MI, Stroke and Non-CNS Systemic Embolism | Time to the first occurrence of composite endpoint of all-cause death, MI, stroke and Non-CNS systemic embolism will be reported. | Up to 4 years | 
| Time to the First Occurrence of Composite Endpoint of CV Death, MI, Stroke, Acute Limb Ischemia (ALI), and Urgent Hospitalization for Vascular cause of Ischemic Nature | Time to the first occurrence of composite endpoint of CV death, MI, stroke, ALI [any unanticipated revascularization or amputation of ischemic limb]), and urgent hospitalization for vascular cause of ischemic nature (including deep vein thrombosis [DVT] and pulmonary embolism [PE]) will be reported. | Up to 4 years |