A Study to Test Asundexian to Prevent a Clot-related Stroke in Participants After an Acute Ischemic Stroke or High-risk TIA/Mini-stroke (Transient Ischemic Attack)

Study Overview
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Brief Summary
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Researchers are looking for a better way to prevent an ischemic stroke which occurs when a blood clot travelled to the brain in people who within the last 72 hours had: an acute stroke due to a blood clot that formed outside the heart (acute non-cardioembolic ischemic stroke), or TIA/mini-stroke with a high risk of turning into a stroke (high-risk transient ischemic attack), and who are planned to receive standard of care therapy. Acute ischemic strokes or TIA/mini-stroke result from a blocked or reduced blood flow to a part of the brain. They are caused by blood clots that travel to the brain and block the vessels that supply it. If these blood clots form elsewhere than in the heart, the stroke is called non-cardioembolic. People who already had a non-cardioembolic stroke are more likely to have another stroke. This is why they are treated preventively with an antiplatelet therapy, the current standard of care. Antiplatelet medicines prevent platelets, components of blood clotting, from clumping together. Anticoagulants are another type of medicine that prevents blood clots from forming by interfering with a process known as coagulation (or blood clotting). The study treatment asundexian is a new type of anticoagulant currently under development to provide further treatment options. Asundexian aims to further improve the standard of care without increasing the risk of bleeding. The main purpose of this study is to learn whether asundexian works better than placebo at reducing ischemic strokes in participants who recently had a non-cardioembolic ischemic stroke or TIA/mini-stroke when given in addition to standard antiplatelet therapy. A placebo is a treatment that looks like a medicine but does not have any medicine in it. Another aim is to compare the occurrence of major bleeding events during the study between the asundexian and the placebo group. Major bleedings have a serious or even life-threatening impact on a person's health. Dependent on the treatment group, the participants will either take asundexian or placebo as tablets once a day for at least 3 months up to 31 months. Approximately every 3 months during the treatment period, either a phone call or a visit to the study site is scheduled on an alternating basis. In addition, one visit before and up to two visits after the treatment period are planned. During the study, the study team will: Check vital signs such as blood pressure and heart rate Examine the participants' heart health using an electrocardiogram (ECG) Take blood samples Ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments. In addition, the participants will be asked to complete a questionnaire on quality of life at certain time points during the study.

Official Title
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A Multicenter, International, Randomized, Placebo Controlled, Double-blind, Parallel Group and Event Driven Phase 3 Study of the Oral FXIa Inhibitor Asundexian (BAY 2433334) for the Prevention of Ischemic Stroke in Male and Female Participants Aged 18 Years and Older After an Acute Non-cardioembolic Ischemic Stroke or High-risk TIA

Conditions
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Prevention of Ischemic Stroke, Acute Non-cardioembolic Ischemic Stroke, High-risk Transient Ischemic Attack

Intervention / Treatment
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* Drug: Asundexian (BAY2433334)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be ≥ 18 years of age Acute non-cardioembolic stroke or high-risk TIA Systemic or cerebrovascular atherosclerosis or acute non-lacunar infarct Exclusion Criteria: Ischemic stroke ≤ 7 days before the index stroke event Index stroke following procedures or strokes due to other rare causes History of atrial fibrillation/flutter, left ventricular thrombus, mechanic valve or other cardioembolic source of stroke requiring 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Asundexian<br>Participants will receive asundexian. | Drug: Asundexian (BAY2433334)<br>* Once daily, oral<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo. | Drug: Placebo<br>* Placebo to asundexian, once daily, oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first occurrence of ischemic stroke |  | Up to 31 months | 
| Time to first occurrence of ISTH major bleeding | ISTH=International Society on Thrombosis and Hemostasis | Up to 31 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first occurrence of all strokes (ischemic and hemorrhagic) |  | Up to 31 months | 
| Time to first occurrence of composite of CV death, MI or stroke | CV=Cardiovascular, MI=Myocardial infarction | Up to 31 months | 
| Time to first occurrence of composite of all-cause mortality, MI or stroke |  | Up to 31 months | 
| Time to first occurrence of disabling stroke (mRS ≥3 at 90 days) | mRS=Modified Rankin Scale | Up to 31 months | 
| Time to first occurrence of all-cause mortality |  | Up to 31 months | 
| Time to first occurrence of transient ischemic attack (TIA) |  | Up to 31 months | 
| Time to first occurrence of composite of ISTH major or clinically relevant non-major bleeding |  | Up to 31 months | 
| Time to first occurrence of ISTH clinically relevant non-major bleeding |  | Up to 31 months | 
| Time to first occurrence of symptomatic intracranial hemorrhage |  | Up to 31 months | 
| Time to first occurrence of hemorrhagic stroke |  | Up to 31 months | 
| Time to first occurrence of fatal bleeding |  | Up to 31 months | 
| Time to first occurrence of minor bleeding |  | Up to 31 months | 
| Time to first occurrence of composite of ischemic stroke or ISTH major bleeding |  | Up to 31 months | 
| Time to first occurrence of composite of CV death, all stroke, MI or ISTH major bleeding |  | Up to 31 months | 
| Time to first occurrence of composite of all-cause mortality, disabling stroke, fatal bleeding, symptomatic intracranial hemorrhage |  | Up to 31 months |