E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-cardioembolic ischemic stroke |
ICTUS non cardioembolico |
|
E.1.1.1 | Medical condition in easily understood language |
Stroke which occurs when a blood clot has formed somewhere in the human body (but not in the heart) travelled to the brain |
infarto cerebrale |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 |
• To assess the dose response of 3 different doses of BAY 2433334 compared to placebo in reducing the composite of symptomatic ischemic strokes and covert brain infarcts detected by MRI as well as other cerebro- and cardiovascular endpoints in participants with an acute non-cardioembolic ischemic stroke and who are treated with antiplatelet therapy. • To evaluate whether the incidence of bleeding is similar for BAY 2433334 compared to placebo in participants with an acute non-cardioembolic ischemic stroke and who are treated with antiplatelet therapy. |
• E.2.1 Obiettivo principale: valutare la risposta a 3 dosi diverse di BAY 2433334 rispetto al placebo nella riduzione dell’endpoint composito di ictus ischemici sintomatici e infarti cerebrali silenti rilevati mediante risonanza magnetica (RM) e di altri endpoint di natura cerebrovascolare e cardiovascolare in partecipanti con ictus ischemico non cardioembolico acuto trattati con la terapia antiaggregante. • valutare se l’incidenza del sanguinamento sia simile tra BAY 2433334 e il placebo nei partecipanti con ictus ischemico non cardioembolico acuto trattati con la terapia antiaggregante. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
1. Al momento della sottoscrizione del consenso informato il partecipante deve avere almeno 45 anni 2. Ictus ischemico non cardioembolico con a. segni e sintomi persistenti di ictus con durata = 24 ore OPPURE b. infarto cerebrale acuto documentato da tomografia computerizzata (TC) o risonanza magnetica (RM) E c. con intenzione di trattamento con terapia antipiastrinica durante lo studio 3. Imaging cerebrale (TC o RM) che escluda ictus emorragico o altra patologia rispondente ai sintomi (es. tumore al cervello, ascesso, malformazione vascolare) 4. Gravità dell’evento indice più vicino al momento della randomizzazione: a. Parte A: possono essere arruolati partecipanti con ictus minore (punteggio NIHSS = 7). b. Parte B: possono essere arruolati partecipanti con ictus minore o moderato e punteggio NIHSS = 15. I partecipanti sottoposti a trombolisi o a terapia endovascolare (trombectomia meccanica) possono essere arruolati ma non prima di 24 ore dall’intervento. 5. Randomizzazione entro 48 ore dall’insorgenza dei sintomi dell’evento indice (o dall’ultimo momento in cui non erano presenti sintomi in caso di ictus al risveglio) 6. Capacità di effettuare una RM prima della randomizzazione o entro 72 ore dalla randomizzazione |
|
E.4 | Principal 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 |
1. Ictus ischemico precedente negli ultimi 30 giorni dall’evento indice 2. Anamnesi di fibrillazione atriale o sospetto di causa cardioembolica dell’ictus 3. Disfagia con incapacità di deglutire in modo sicuro il farmaco di studio al momento della randomizzazione 4. Controindicazioni per eseguire la RM cerebrale 5. Solo parte A: trombolisi o terapia endovascolare (trombectomia meccanica) eseguita per l’evento indice 7. Emorragia attiva; disturbo emorragico noto, anamnesi di emorragia grave (intracranica, retroperitoneale, intraoculare) o emorragia gastrointestinale clinicamente significativa negli ultimi 6 mesi di randomizzazione |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: Number of participants with symptomatic ischemic stroke or covert brain infarcts detected by MRI
Primary Safety Endpoint: Time from randomization to first occurrence of International Society on Thrombosis and Hemostasis (ISTH) major bleeding and clinically relevant non-major (CRNM) bleeding |
Endpoint primario di efficacia • composito di ictus ischemico sintomatico e infarto cerebrale silente rilevato mediante RM
Endpoint primario di sicurezza • composito di sanguinamenti maggiori e sanguinamenti non maggiori clinicamente rilevanti (CRNM) secondo i criteri dell’International Society on Thrombosis and Hemostasis (ISTH) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Efficacy Endpoint: From baseline up to 6 months
Primary Safety Endpoint: From baseline up to 12 months |
Endpoint Primario Efficacia : da basale fino a 6 mesi Endpoint Primario Sicurezza: da basale fino a 12 mesi |
|
E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints: 1.Number of participants with composite of symptomatic ischemic stroke and covert brain infarcts detected by MRI, CV death, myocardial infarction and systemic embolism 2.Number of participants with covert brain infarcts detected by MRI 3.Time from randomization to first occurrence of symptomatic ischemic stroke 4.Time from randomization to first occurrence of symptomatic ischemic stroke, CV death, myocardial infarction 5.Time from randomization to first occurrence of symptomatic ischemic and hemorrhagic stroke 6.Time from randomization to first occurrence of disabling stroke (mRS=4) 7.Time from randomization to all-cause mortality
Secondary Safety Endpoints 1. Time from randomization to first occurrence of all bleeding 2. Time from randomization to first occurrence of ISTH major bleeding 3. Time from randomization to first occurrence of ISTH CRNM bleeding 4. Time from randomization to first occurrence of ISTH minor bleeding 5. Time from randomization to first occurrence of Intracerebral hemorrhage (non-traumatic) |
Endpoint secondario di efficacia • composito di ictus ischemico sintomatico e infarto cerebrale silente rilevati mediante RM, morte CV, infarto miocardico ed embolia sistemica • ictus ischemico sintomatico • infarti cerebrali silenti rilevati mediante RM • ictus ischemico sintomatico, morte CV, infarto miocardico • ictus ischemico ed emorragico sintomatico • ictus invalidante (mRS=4) • mortalità per qualsiasi causa Endpoint secondario di sicurezza • tutti i sanguinamenti • sanguinamenti maggiori secondo i criteri ISTH • sanguinamenti CRNM secondo i criteri ISTH • sanguinamenti minori secondo i criteri ISTH • emorragia cerebrale (non traumatica) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline up to 12 months |
Da basale a 12 mesi |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
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 | Yes |
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 |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Definizione della dose |
Dose-finding |
|
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 | 4 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 166 |
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 | Information not present in EudraCT |
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 |
Australia |
Canada |
China |
Japan |
Russian Federation |
United States |
Austria |
Belgium |
Bulgaria |
Denmark |
Finland |
France |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Portugal |
Slovakia |
Spain |
Sweden |
Switzerland |
United Kingdom |
Czechia |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 29 |