Multicenter, Randomized,Placebo-controlled, Double-blind, Parallel Group, Dose-finding Phase 2 Study to Evaluate Efficacy and Safety of BAY2433334 in Patients Following an Acute Non-cardioembolic Ischemic Stroke

Phase 2

Completed

• Conditions: An acute non-cardioembolic ischemic stroke

• Registration Number: JPRN-jRCT2080225214
• Lead Sponsor: Bayer Yakuhin, Ltd.

Brief Summary

Efficacy: The primary efficacy objective was not met as a dose-response relationship for the primary endpoint could not be shown. A favorable trend for the secondary efficacy endpoint of symptomatic ischemic stroke was seen for asundexian compared to placebo, in particular, for participants with signs of atherosclerosis. Safety: The bleeding risk of asundexian was favorable even with near complete inhibition of FXIa activity in the 50 mg asundexian dose group.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-06-01
• Study Completion: 2022-02-17
• Results First Posted: 2022-08-28
• Last Update Posted: 20 November 2023

Recruitment & Eligibility

• Status: completed
• Sex: All
• Target Recruitment: 1808

Inclusion Criteria

Inclusion Criteria:
-Participant must be 45 years of age and older at the time of signing the informed consent
-Non-cardioembolic ischemic stroke with
persistent signs and symptoms of stroke lasting for >= 24 hours OR
acute brain infarction documented by computed tomography (CT) or MRI AND
with the intention to be treated with antiplatelet therapy during the study conduct
-Imaging of brain (CT or MRI) ruling out hemorrhagic stroke or another pathology that could explain symptoms (e.g. brain tumor, abscess, vascular malformation)
-Severity of index event nearest the time of randomization:
Part A: minor stroke (defined as National Institutes of Health Stroke Scale (NIHSS) =< 7) can be enrolled
Part B: participants with minor or moderate stroke and NIHSS =< 15 can be enrolled. Participants undergoing thrombolysis or endovascular therapy (mechanical thrombectomy) can be enrolled but at the earliest 24 hours after the intervention
-Randomization within 48 hours after the onset of symptoms of the index event (or after patients were last known to be without symptoms in case of wake-up stroke)
-Ability to conduct an MRI either before randomization or within 72 hours after randomization

Exclusion Criteria

Exclusion Criteria:
-Prior ischemic stroke within last 30 days of index event
-History of atrial fibrillation or suspicion of cardioembolic source of stroke
-Dysphagia with inability to safely swallow study medication
-Contraindication to perform brain MRI
-Part A only: thrombolysis or endovascular therapy (mechanical thrombectomy) performed for index event
-Active bleeding; known bleeding disorder, history of major bleeding (intracranial, retroperitoneal, intraocular) or clinically significant gastrointestinal bleeding within last 6 months of randomization

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
safety<br>efficacy<br>-Number of participants with symptomatic ischemic stroke or covert brain infarcts detected by Magnetic resonance imaging (MRI) [ Time Frame: From baseline up to 6 months ]<br>-Time from randomization to first occurrence of International Society on Thrombosis and Hemostasis (ISTH) major bleeding and clinically relevant non-major (CRNM) bleeding [ Time Frame: From baseline up to 12 months ]