A Phase 3 Placebo-controlled Study of Milvexian after an Acute Ischemic Stroke or High-Risk Transient Ischemic Attack
- Conditions
- Acute Ischemic Stroke and High-Risk Transient Ischemic AttackMedDRA version: 20.0Level: PTClassification code: 10007649Term: Cardiovascular disorder Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- CTIS2022-501176-26-00
- Lead Sponsor
- Janssen - Cilag International
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 15000
Age =40 years of age, Ischemic Stroke: a neurological deficit attributable to an acute brain infarction and NIHSS score = 7 and at least 1 of the following: Persistent signs or symptoms of the ischemic event at the time of randomization, OR Acute, ischemic brain lesion determined by standard-of-care neuroimaging OR Participant underwent thrombolysis or thrombectomy OR TIA: acute onset neurological deficit attributable to focal ischemia of the brain by history or examination, with complete symptom resolution of the deficit and no brain infarction on neuroimaging (eg, CT scan or MRI, performed as part of standard medical practice), and ABCD2 Score =6, Participants will be randomized as soon as possible after determining eligibility and within 48 hours of onset of event. In participants in whom a stroke was evident on awakening from sleep, within 48 hours from the time at which the participants’ condition was last reported to be normal. Participants who received thrombolysis and/or mechanical thrombectomy with or without stenting can be randomized but only after 24 hours have elapsed after the end of this treatment and not more than 48 hours after the onset of the index event, and provided that post-treatment neuroimaging excludes cerebral bleeding and have postthrombolytic therapy/post-thrombectomy INR = 1.5 and aPTT = 1.4 times the ULN prior to study randomization. Cerebrovascular vessel stenting is allowed as clinically indicated. If these procedures are done pre-randomization, then randomization should occur at least 24 hours after the end of the procedure and not more than 48 hours after the onset of the index event., Current or planned antiplatelet treatment per international and/or local guidelines. If ASA is used, it will be limited to low dose (75 to 100 mg/day). Loading dose of antiplatelet agents (including ASA) are allowed per standard-of-care, A female participant must be a. Not of childbearing potential or b. Of childbearing potential and practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) and agrees to remain on a highly effective method until 4 days (5 half lives) after last dose of study intervention –the end of relevant exposure. The investigator must evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention.
Current intracranial hemorrhage (hemorrhage into the brain, subarachnoid hemorrhage, intraventricular hemorrhage, subdural hematoma or epidural hematoma); except CMB and minor hemorrhagic transformation of infarct manifesting as scattered petechiae (Hemorrhagic Infarction Type 1 [HI1] according to Heidelberg classification)., Prior history of intracranial hemorrhage except subarachnoid hemorrhage > 1 year prior with adequate treatment., The index stroke or TIA is considered to have a cardio-embolic etiology based on local standard-of-care investigations and for which guidelines recommend anticoagulation., The index stroke or TIA considered to have an other known cause, not related to athero-thrombotic sources (TOAST Other Determined Etiology) based on local standard-of-care investigations. Examples of such etiologies include intracranial tumor, arteritis, arterial dissection, vasospasm or AVM., Pre-event disability with mRS score of 3 or higher., Any condition that requires chronic anticoagulation at the discretion of the investigator and/or local guidelines. Note: Participants with an indication for chronic antiplatelet therapy after placement of a bio-prosthetic nonmechanical valve (eg, transcatheter aortic valve replacement [TAVR]) do not satisfy this exclusion criterion and are eligible for study participation, Conditions with an increased risk of bleeding, including: Clinically significant bleeding within the previous 3 months Known bleeding diathesis Known aPTT prolongation > 1.4 times the ULN or known congenital FXI deficiency Spinal cord hemorrhage Retinal hemorrhage, eGFR <15 mL/min/1.73 m2 at screening, Any of the following laboratory results, based on local laboratory, outside of the ranges specified below prior to randomization: ALT ? 3X ULN Platelet count <75,000 mm3 Total bilirubin = 1.5x ULN unless an alternative causative factor such as Gilbert’s syndrome is identified Hemoglobin <8.0 g/d
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate if milvexian reduces the risk of ischemic stroke, compared with placebo;Secondary Objective: To evaluate if milvexian reduces the risk of CVD, MI, or ischemic stroke, compared with placebo, To evaluate if milvexian reduces the risk of ischemic stroke in the first 90 days compared with placebo, To evaluate if milvexian reduces the risk of MAVE (ie, the composite of CVD, MI, ischemic stroke, MALE [ie, major (nontraumatic) vascular limb amputation, or acute limb ischemia], symptomatic PE or DVT) compared with placebo;Primary end point(s): Time to first occurrence of ischemic stroke
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Time to first occurrence of any component of the composite of CVD, MI, or ischemic stroke;Secondary end point(s):Time to first occurrence of ischemic stroke in the first 90 days;Secondary end point(s):Time to first occurrence of any component of MAVE (ie, composite of CVD, MI, ischemic stroke, MALE, symptomatic PE or DVT)