E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of ischemic stroke in patients post acute non-cardioembolic ischemic stroke or high-risk transient ischemic attack |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of ischemic stroke in people after such a stroke due to a blood clot that formed outside the heart (non-cardioembolic) and travelled to the brain, or after temporary stroke-like symptoms |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049165 |
E.1.2 | Term | Cerebrovascular accident prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 22.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055221 |
E.1.2 | Term | Ischemic stroke |
E.1.2 | System Organ Class | 100000004852 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072760 |
E.1.2 | Term | Transient ischemic attack |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy To evaluate whether the oral FXIa inhibitor asundexian is superior to placebo on top of background antiplatelet therapy in reducing ischemic stroke in patients after an acute non-cardioembolic ischemic stroke or high-risk Transient ischemic attack (TIA)
Safety To compare the incidence of International Society on Thrombosis and Hemostasis (ISTH) major bleeding for asundexian and placebo on top of antiplatelet therapy in patients after an acute noncardioembolic ischemic stroke or high-risk TIA |
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E.2.2 | Secondary objectives of the trial |
Efficacy To evaluate whether asundexian is superior to placebo on top of antiplatelet therapy in reducing the occurrence of composite and individual efficacy endpoints
Safety To compare asundexian and placebo on top of antiplatelet therapy with respect to individual bleeding endpoints
Net clinical benefit To further compare the benefit and risk of asundexian and placebo with respect to a composite of efficacy and safety endpoints |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Magnetic resonance imaging (MRI) Sub-study: to correlate baseline MRI findings with future events (e.g. covert brain infarction, recurrent strokes, intracranial bleeding), identify asundexian responders, further characterize the study population by MRI and add additional safety information on the asundexian 50 mg dose (to the Phase 2 study). |
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E.3 | Principal inclusion criteria |
1. Participants must be ≥ 18 years of age 2. Acute non-cardioembolic stroke or high-risk TIA 3. Systemic or cerebrovascular atherosclerosis or acute non-lacunar infarct |
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E.4 | Principal exclusion criteria |
1. Ischemic stroke ≤ 7 days before the index stroke event 2. Index stroke following procedures or strokes due to other rare causes 3. History of atrial fibrillation/flutter, left ventricular thrombus, mechanic valve or other cardioembolic source of stroke requiring anticoagulation |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Time to first occurrence of ischemic stroke 2. Time to first occurrence of ISTH major bleeding |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Time to first occurrence of all strokes (ischemic and hemorrhagic) 2. Time to first occurrence of composite of Cardiovascular (CV) death, myocardial infarction (MI) or stroke 3. Time to first occurrence of composite of all-cause mortality, MI or stroke 4. Time to first occurrence of disabling stroke (mRS ≥3 at 90 days) 5. Time to first occurrence of all-cause mortality 6. Time to first occurrence of transient ischemic attack (TIA) 7. Time to first occurrence of composite of ISTH major or clinically relevant non-major bleeding 8. Time to first occurrence of ISTH clinically relevant non-major bleeding 9. Time to first occurrence of symptomatic intracranial hemorrhage 10. Time to first occurrence of hemorrhagic stroke 11. Time to first occurrence of fatal bleeding 12. Time to first occurrence of minor bleeding 13. Time to first occurrence of composite of ischemic stroke or ISTH major bleeding 14. Time to first occurrence of composite of CV death, all stroke, MI or ISTH major bleeding 15. Time to first occurrence of composite of all-cause mortality, disabling stroke, fatal bleeding, symptomatic intracranial hemorrhage |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 289 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
Canada |
China |
Colombia |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Taiwan |
United States |
Austria |
Finland |
France |
Latvia |
Lithuania |
Poland |
Sweden |
Bulgaria |
Netherlands |
Romania |
Spain |
Switzerland |
Czechia |
Germany |
Greece |
Italy |
Belgium |
Denmark |
Hungary |
Norway |
Portugal |
Slovakia |
Turkey |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date of the last visit of the last subject in the study globally (LVLS). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |