Ischemic Stroke or Transient Ischemic Attack (TIA) MedDRA version: 20.0 Level: PT Classification code 10044390 Term: Transient ischaemic attack System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10061256 Term: Ischaemic stroke System Organ Class: 10029205 - Nervous system disorder
Conditions
Interventions
Product Name: BMS-986177
Product Code: BMS-986177
Pharmaceutical Form: Capsule
INN or Proposed INN: _
CAS Number: 1802425-99-5
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent a) Participants =40 years of age (or legally acceptable representatives, as per country guidelines) from whom a signed and dated written consent for participation has been obtained. 2) Type of Participant and Target Disease Characteristics a) Ischemic stroke: a neurological deficit attributable to a non-lacunar acute brain infarction detected by MRI and relevant to the clinical symptoms AND National Institutes of Health Stroke Score (NIHSS) =5 AND Acute brain infarction distal to an intracranial or cervical arterial atherosclerotic plaque or aortic arch atheroma >4 mm in thickness, ulceration or thrombus documented by imaging (Doppler ultrasound, CTA, MRA or catheter angiography) AND Modified Rankin Score (mRS) =3 before the index event b) TIA: acute onset neurological deficit attributable to focal ischemia of the brain by history or examination, with complete resolution of the deficit and no brain infarction on MRI AND ABCD2 Score =6^3 or motor symptoms AND Symptoms attributable to an intracranial or cervical arterial atherosclerotic plaque or aortic arch atheroma >4 mm in thickness, ulceration or thrombus documented by imaging (Doppler ultrasound, CTA, MRA or catheter angiography) 3) The participant must be able to be evaluated by study-specific MRI within 48 hours of index event and prior to randomization. Therefore, participants must have a body habitus suitable for MRI and cannot have any contraindications to the performance of the MRI (see Section 7.7.2.1). 4) No contraindication to clopidogrel or aspirin and suitable for treatment with aspirin 100 mg per day for at least 90 days 5) Age and Reproductive Status a) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment. b) Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with BMS-986177 plus 5 halflives of study treatment plus 30 days (duration of ovulatory cycle) for a total of 32 days post-treatment completion c) Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception (Appendix 4) for the duration of treatment with study treatment BMS-986177, plus 5 half-lives of the study treatment, plus 90 days (duration of sperm turnover) for a total of 4 days post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time. d) Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active, or are not of childbearing potential, are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section. e) Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators
Exclusion criteria
Exclusion criteria: 1) Medical Conditions a) Predicted inability to swallow study medication b) Women who are pregnant or breastfeeding c) Any condition that, in the opinion of the Investigator, contraindicates anticoagulant therapy or would have an unacceptable risk of bleeding such as a large infarct volume (per Investigator discretion) or uncontrolled hypertension. d) Hemorrhage, tumor, arteritis, large vessel dissection, arteriovenous malformation (AVM) or other pathology that could account for index symptoms must be excluded by CT or MRI interpreted locally. e) Symptomatic carotid stenosis for which endarterectomy or stenting is planned within 90 days f) Use of thrombolytic therapy or mechanical thrombectomy for treatment of index event g) Any condition for which chronic anticoagulation is recommended h) Requirement for continued use of dual antiplatelet therapy (DAPT) for more than 21 days or non-aspirin antiplatelet therapy or anticoagulant for another medical condition (e.g. prophylaxis for venous thromboembolism). Note: Treatment with clopidogrel, aspirin, dipyridamole or another P2Y12 inhibitor prior to enrollment is allowed. Treatment with aspirin at a different dose before enrollment is also allowed. All participants must transition to the protocol-defined treatments and doses at randomization. No clopidogrel loading dose is needed for participants who received a clopidogrel loading dose prior to randomization. Participants who report taking chronic clopidogrel also require a 300-mg clopidogrel loading dose unless the Investigator can verify that the patient has taken the daily dose for at least the preceding 3 days. Participants who have received dipyridamole or another P2Y12 inhibitor must receive the clopidogrel loading dose after discontinuing the non-clopidogrel P2Y12 inhibitor or dipyridamole/dipyridamole-containing treatment. i) History of hemorrhage into the brain, subarachnoid hemorrhage, subdural hematoma or spinal cord hemorrhage except cerebral microbleeds (CMB) and petechiae on imaging. Note: CMBs are defined as rounded foci of 5 mm l) History of end stage renal disease (ESRD) with eGFR <15 mL/min/m2, or requiring dialysis 2) Prior/Concomitant Therapy a) Any investigational drug or placebo exposure within 4 weeks of study drug administration b) Any prior exposure to BMS-986177 c) Planned use of anticoagulants including warfarin or other vitamin K antagonists, oral thrombin and Factor Xa inhibitors, bivalirudin, hirudin, argatroban, unfractionated and low molecular weight heparins, with the exception of heparin or low molecular weight heparin (LMWH) used to maintain patency of indwelling catheters. Note: Participants who received 1 or 2 doses of UFH or LMWH for DVT prophylaxis prior to enrollment can be randomized. T
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the dose-response relationship of BMS-986177, by identifying a MED(a) and ED90(b), in participants with ischemic stroke or TIA treated with aspirin + clopidgrel.; Secondary Objective: To assess the rate of major bleeding after treatment with BMS-986177 relative to placebo To assess the rate of all bleeding after treatment with BMS-986177 relative to placebo To compare the rate of the composite of new ischemic stroke and new covert brain infarction detected by MRI at 90 days on treatment with BMS-986177 compared to placebo To assess the effect of BMS-986177 on characteristics of brain lesions on Day 90 MRI To compare the rate of the composite of new ischemic stroke, myocardial infarction (MI) and all-cause mortality during treatment with BMS-986177 vs. placebo To assess stroke severity, neurological, and cognitive function following BMS-986177 treatment vs. placebo To assess the safety and tolerability of BMS-986177 To assess the pharmacokinetics (PK) of BMS-986177 and potential effects of covariates on exposure To assess the dose-response of BMS-986177 on pharmacodynamic (PD) biomarkers ;Primary end point(s): Composite of new ischemic stroke during the treatment period and new covert brain infarction (FLAIR + DWI) detected by MRI at 90 days;Timepoint(s) of evaluation of this end point: MRI at 90 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Event rate based on bleeding according to Bleeding Academic Research Consortium (BARC) Type 3 and 5 Event rate based on BARC, ISTH and PLATO-defined criteria Rate of the composite of new ischemic stroke during the treatment period and new covert brain infarction (FLAIR + DWI) detected by MRI at 90 days Location, number, and volume of new FLAIR + DWI lesions Event rates for new ischemic, non-fatal stroke, non-fatal MI, and all-cause death during the treatment period National Institutes of Health Stroke Scale (NIHSS) Modified Rankin Scale (mRS), Montreal Cognitive Assessment (MoCA), and Digital Symbol Substitution Test (subtest of WAIS-IV) at baseline, on days 21 and 90, and at the time of a new stroke event. Adverse events, vital signs, physical exams,electrocardiogram (ECG) and clinical laboratory results Estimated clearance (CL) and volume of distribution (Vd) and effect of body weight, age, gender, race, renal function, liver function, concomitant medications % change from baseline in aPTT and Factor XI clotting activity during treatment ; Timepoint(s) of evaluation of this end point: During the treatment period (90 days) During the treatment period (90 days) MRI at 90 days MRI at 90 days During the treatment period (90 days) NIHSS, MoCA, and DSST on Days 21 and 90, and at the time of a new stroke event. mRS and BI on Days 21 and 90 only During the treatment period (90 days) During the treatment period (90 days) During the treatment period (90 days) | — |
Countries
Canada, Czech Republic, France, Germany, Hungary, Spain, United States
Contacts
Public ContactGCT-SU
Bristol-Myers Squibb International Corporation
Outcome results
None listed