A Study of Milvexian in Participants After an Acute Ischemic Stroke or High-Risk Transient Ischemic Attack- LIBREXIA-STROKE

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate whether milvexian compared to placebo reduce the risk of recurrent ischemic stroke.

Official Title
-----------------
A Phase 3, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Demonstrate the Efficacy and Safety of Milvexian, an Oral Factor XIa Inhibitor, for Stroke Prevention After an Acute Ischemic Stroke or High-Risk Transient Ischemic Attack

Conditions
-----------------
Ischemic Stroke; Ischemic Attack, Transient

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ischemic Stroke: a neurological deficit attributable to an acute brain infarction and national institute of health stroke score scale (NIHSS) score less than or equal to (<=) 7 and at least 1 of the following: persistent signs or symptoms of the ischemic event at the time of randomization, or acute, ischemic brain lesion determined by standard-of-care neuroimaging, or participant underwent thrombolysis or thrombectomy, or transient ischemic attack (TIA): acute onset neurological deficit attributable to focal ischemia of the brain by history or examination, with complete symptom resolution of the deficit and no brain infarction on neuroimaging (example, computed tomography (CT) scan or magnetic resonance imaging (MRI), performed as part of standard medical practice), and ABCD2 Score greater than or equal to (>=) 6 Participants will be randomized as soon as possible after determining eligibility and within 48 hours of onset of event. Current or planned antiplatelet treatment per international and/or local guidelines. If acetyl salicylic acid (ASA) is used, it will be limited to low dose (75 to 100 milligrams (mg)/day). Loading dose of antiplatelet agents (including ASA) are allowed per standard-of-care A female participant must agree not to be pregnant, breastfeeding, or planning to become pregnant until 4 days (5 half lives) after the last dose of study intervention Willing and able to adhere to the lifestyle restrictions specified in this protocol Exclusion Criteria: Prior history of intracranial hemorrhage except subarachnoid hemorrhage greater than (>) 1 year prior with adequate treatment The index stroke or TIA is considered to have a cardio-embolic etiology based on local standard-of-care investigations and for which guidelines recommend anticoagulation The index stroke or TIA considered to have another known cause, not related to athero-thrombotic sources (treatment of acute stroke trial [TOAST] Other Determined Etiology), based on local standard-of-care investigations Increased risk of bleeding, including clinically significant bleeding within the previous 3 months or known bleeding diathesis or known activated partial thromboplastin time (aPTT) prolongation or spinal cord hemorrhage or retinal hemorrhage Current active liver disease, eg, acute hepatitis, known cirrhosis, including participants receiving antiviral treatment for hepatitis Known allergies, hypersensitivity, or intolerance to milvexian or its excipients

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Milvexian<br>Participants after an acute ischemic stroke or high-risk transient ischemic attack (TIA) who are receiving antiplatelet therapy standard-of-care (SAPT [single antiplatelet therapy] or DAPT [dual antiplatelet therapy]) will receive milvexian 25 milligrams (mg), orally, twice daily. | Drug: Milvexian<br>* Milvexian will be administered orally.<br>* Other names: JNJ-70033093, BMS-986177;|
| Placebo Comparator: Placebo<br>Participants after an acute ischemic stroke or high-risk TIA who are receiving antiplatelet therapy standard-of-care (SAPT or DAPT) will receive placebo orally twice daily. | Drug: Placebo<br>* Placebo will be administered orally<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Occurrence of Ischemic Stroke | Time to first occurrence of ischemic stroke will be reported. | Up to global targeted endpoint date (approximately 41 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Occurrence of any Component of the Composite of Cardiovascular Death (CVD), Myocardial Infraction (MI), or Ischemic Stroke | Time to first occurrence of any component of the composite of CVD, MI, or ischemic stroke will be reported. | Up to global targeted endpoint date (approximately 41 months) | 
| Time to First Occurrence of Ischemic Stroke | Time to first occurrence of ischemic stroke in the first 90 days will be reported. | Up to Day 90 | 
| Time to First Occurrence of any Component of Major Adverse Vascular Events (MAVE) | Time to first occurrence of any component of MAVE will be reported. MAVE is a composite of (CVD), myocardial infarction (MI), ischemic stroke, major adverse limb events (MALE), symptomatic pulmonary embolism (PE) or deep vein thrombosis (DVT). | Up to global targeted endpoint date (approximately 41 months) |