The main objective of the study is to explore whether the addition of BAY 2433334 will lead to a dose response in reducing symptomatic strokes and covert brain infarcts and whether this is combined with no relevant increase in bleeding when given on…
ID
Source
Brief title
Condition
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Composite of symptomatic ischemic stroke and covert brain infarcts detected by
MRI.
Composite of International Society on Thrombosis and Hemostasis (ISTH) major
bleeding and clinically relevant non-major (CRNM) bleeding
Secondary outcome
Composite of symptomatic ischemic stroke and covert brain infarcts detected by
MRI, CV death, myocardial infarction and systemic embolism
Incidence of covert brain infarcts detected by MRI
Hazard ratio of symptomatic ischemic stroke
Hazard ratio of symptomatic ischemic stroke, CV death, myocardial infarction
Hazard ratio of symptomatic ischemic and hemorrhagic stroke
Hazard ratio of disabling stroke
Hazard ratio of all-cause mortality
Hazard ratio of all bleeding
Hazard ratio of ISTH major bleeding
Hazard ratio of ISTH CRNM bleeding
Hazard ratio of ISTH minor bleeding
Hazard ratio of Intracerebral hemorrhage (nontraumatic)
Background summary
Currently, patients with non-cardioembolic ischemic stroke are treated with
antiplatelet therapy. No clinical studies have proven the benefit of
anticoagulation therapy in patients with non-cardioembolic stroke. However, it
has been shown that patients with a stroke have increased levels of FXI and
patients with FXI deficiency have a lower risk for stroke. Inhibition of FXIa
is expected to lead to a benefit versus placebo regarding secondary prevention
of ischemic stroke as well as to not lead to a relevant increase in bleeding
and especially major bleeding.
Study objective
The main objective of the study is to explore whether the addition of BAY
2433334 will lead to a dose response in reducing symptomatic strokes and covert
brain infarcts and whether this is combined with no relevant increase in
bleeding when given on top of antiplatelet therapy. An additional objective is
to guide dose selection for Phase 3.
Study design
Multicenter, randomized, placebo-controlled, double-blind, parallel group,
dose-finding Phase 2 study to evaluate efficacy and safety of BAY 2433334 in
patients following an acute non-cardioembolic ischemic stroke.
Intervention
- BAY 2433334 high dose (oral, tablet, once daily)
- BAY 2433334 medium dose (oral, tablet, once daily)
- BAY 2433334 low dose (oral, tablet, once daily)
- placebo (oral, tablet, once daily)
Study burden and risks
The safety profile of BAY 2433334 is not yet determined. The following safety
and risk information is available:
- A risk for bleeding cannot be excluded.
- increases in liver enzymes was shown in animal studies.
- strong CYP3A4 inhibitors and inducers cannot be used in combination with BAY
2433334, as this increases the exposure to BAY 2433334 and leads to prolonged
half-life of BAY 2433334.
Energieweg 1
Mijdrecht 3641RT
NL
Energieweg 1
Mijdrecht 3641RT
NL
Listed location countries
Age
Inclusion criteria
1. Participant must be 45 years of age and older at the time of signing the
informed consent
2. Non-cardioembolic ischemic stroke with
a. persistent signs and symptoms of stroke lasting for * 24 hours OR
b. acute brain infarction documented by computed tomography (CT) or MRI AND
c. with the intention to be treated with antiplatelet therapy during the
study conduct
3. Imaging of brain (CT or MRI) ruling out hemorrhagic stroke or another
pathology that could explain symptoms (e.g. brain tumor, abscess, vascular
malformation)
4. Severity of index event nearest the time of randomization:
a. Part A: minor stroke (defined as NIHSS * 7) can be enrolled
b. 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
5. 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)
6. Ability to conduct an MRI either before randomization or within 72 hours
after randomization
Exclusion criteria
1. Prior ischemic stroke within last 30 days of index event
2. History of atrial fibrillation or suspicion of cardioembolic source of stroke
3. Dysphagia with inability to safely swallow study medication at time of
randomization
4. Contraindication to perform brain MRI
5. Part A only: thrombolysis or endovascular therapy (mechanical thrombectomy)
performed for index event
7. Active bleeding; known bleeding disorder, history of major bleeding
(intracranial, retroperitoneal, intraocular) or clinically significant
gastrointestinal bleeding within last 6 months of randomization
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-003431-33-NL |
| CCMO | NL72077.018.19 |