Study to Gather Information About Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following a Recent Non Cardioembolic Ischemic Stroke Which Occurs When a Blood Clot Has Formed Somewhere in the Human Body (But Not in the Heart) Travelled to the Brain. (PACIFIC-STROKE)

• ClinicalTrials.gov Identifier: NCT04304508
• Recruitment Status: Completed
• First Posted: March 11, 2020
• Last Update Posted: June 30, 2022
• Sponsor: Bayer
• Collaborator: Population Health Research Institute
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: March 8, 2020
• First Posted Date: March 11, 2020
• Last Update Posted Date: June 30, 2022
• Actual Study Start Date: June 15, 2020
• Actual Primary Completion Date: February 18, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 8, 2020)

• Number of participants with symptomatic ischemic stroke or covert brain infarcts detected by Magnetic resonance imaging (MRI) [ Time Frame: From baseline up to 6 months ]
• Time from randomization to first occurrence of International Society on Thrombosis and Hemostasis (ISTH) major bleeding and clinically relevant non-major (CRNM) bleeding [ Time Frame: From baseline up to 12 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 9, 2020)

• Number of participants with composite of symptomatic ischemic stroke and covert brain infarcts detected by MRI, Cardiovascular (CV) death, myocardial infarction and systemic embolism [ Time Frame: From baseline up to 6 months ]
• Number of participants with covert brain infarcts detected by MRI [ Time Frame: From baseline up to 6 months ]
• Time from randomization to first occurrence of symptomatic ischemic stroke [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of symptomatic ischemic stroke, CV death, myocardial infarction [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of symptomatic ischemic and hemorrhagic stroke [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of disabling stroke [ Time Frame: From baseline up to 12 months ]
  Modified ranking score (mRS)≥4
• Time from randomization to all-cause mortality [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of all bleeding [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of ISTH major bleeding [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of ISTH CRNM bleeding [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of ISTH minor bleeding [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of Intracerebral hemorrhage (non-traumatic) [ Time Frame: From baseline up to 12 months ]

Original Secondary Outcome Measures (submitted: March 8, 2020)

• Number of participants with composite of symptomatic ischemic stroke and covert brain infarcts detected by MRI, Cardiovascular (CV) death, myocardial infarction and systemic embolism [ Time Frame: From baseline up to 12 months ]
• Number of participants with covert brain infarcts detected by MRI [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of symptomatic ischemic stroke [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of symptomatic ischemic stroke, CV death, myocardial infarction [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of symptomatic ischemic and hemorrhagic stroke [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of disabling stroke [ Time Frame: From baseline up to 12 months ]
  Modified ranking score (mRS)≥4
• Time from randomization to all-cause mortality [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of all bleeding [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of ISTH major bleeding [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of ISTH CRNM bleeding [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of ISTH minor bleeding [ Time Frame: From baseline up to 12 months ]
• Time from randomization to first occurrence of Intracerebral hemorrhage (non-traumatic) [ Time Frame: From baseline up to 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Gather Information About Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following a Recent Non Cardioembolic Ischemic Stroke Which Occurs When a Blood Clot Has Formed Somewhere in the Human Body (But Not in the Heart) Travelled to the Brain.
• Official Title: Multicenter, Randomized, Placebo-controlled, Double-blind, Parallel Group, Dose-finding Phase 2 Study to Evaluate Efficacy and Safety of BAY2433334 in Patients Following an Acute Non-cardioembolic Ischemic Stroke
• Brief Summary: The purpose of this study is to try to find the best dose of the new drug BAY 2433334 to give to participants and to look at how well BAY 2433334 works on top of antiplatelet therapy in patients following a recent non cardioembolic ischemic stroke which occurs when a blood clot that has not formed in the heart travelled to the brain. BAY 2433334, works by blocking a step of the blood clotting process in our body and thins the blood and is a so called oral FXIa inhibitor.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Acute Non-cardioembolic Ischemic Stroke

Intervention

• Drug: BAY2433334
  Tablet, taken orally once a day.
• Other: BAY2433334 matching placebo
  Tablet, taken orally once a day.

Study Arms

• Experimental: BAY2433334 high dose
  Intervention: Drug: BAY2433334
• Experimental: BAY2433334 medium dose
  Intervention: Drug: BAY2433334
• Experimental: BAY2433334 low dose
  Intervention: Drug: BAY2433334
• Placebo Comparator: BAY2433334 matching placebo
  Intervention: Other: BAY2433334 matching placebo

• Publications *: Shoamanesh A, Mundl H, Smith EE, Masjuan J, Milanov I, Hirano T, Agafina A, Campbell B, Caso V, Mas JL, Dong Q, Turcani P, Christensen H, Ferro JM, Veltkamp R, Mikulik R, De Marchis GM, Robinson T, Lemmens R, Stepien A, Greisenegger S, Roine R, Csiba L, Khatri P, Coutinho J, Lindgren AG, Demchuk AM, Colorado P, Kirsch B, Neumann C, Heenan L, Xu L, Connolly SJ, Hart RG; PACIFIC-Stroke Investigators. Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet. 2022 Sep 24;400(10357):997-1007. doi: 10.1016/S0140-6736(22)01588-4. Epub 2022 Sep 2.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 25, 2022): 1808
• Original Estimated Enrollment (submitted: March 8, 2020): 1800
• Actual Study Completion Date: February 18, 2022
• Actual Primary Completion Date: February 18, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participant must be 45 years of age and older at the time of signing the informed consent

• Non-cardioembolic ischemic stroke with

  • persistent signs and symptoms of stroke lasting for ≥ 24 hours OR
  • acute brain infarction documented by computed tomography (CT) or MRI AND
  • with the intention to be treated with antiplatelet therapy during the study conduct
• Imaging of brain (CT or MRI) ruling out hemorrhagic stroke or another pathology that could explain symptoms (e.g. brain tumor, abscess, vascular malformation)

• Severity of index event nearest the time of randomization:

  • Part A: minor stroke (defined as National Institutes of Health Stroke Scale (NIHSS) ≤ 7) can be enrolled
  • 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
• 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)
• Ability to conduct an MRI either before randomization or within 72 hours after randomization

Exclusion Criteria:

• Prior ischemic stroke within last 30 days of index event
• History of atrial fibrillation or suspicion of cardioembolic source of stroke
• Dysphagia with inability to safely swallow study medication
• Contraindication to perform brain MRI
• Part A only: thrombolysis or endovascular therapy (mechanical thrombectomy) performed for index event
• Active bleeding; known bleeding disorder, history of major bleeding (intracranial, retroperitoneal, intraocular) or clinically significant gastrointestinal bleeding within last 6 months of randomization.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 45 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Bulgaria, China, Czechia, Denmark, Finland, France, Germany, Hungary, Italy, Japan, Netherlands, Poland, Portugal, Russian Federation, Slovakia, Spain, Sweden, Switzerland, United Kingdom, United States
• Removed Location Countries: Canada

Administrative Information

• NCT Number: NCT04304508
• Other Study ID Numbers: 19766; 2019-003431-33 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

Plan Description

Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

• Current Responsible Party: Bayer
• Original Responsible Party: Same as current
• Current Study Sponsor: Bayer
• Original Study Sponsor: Same as current
• Collaborators: Population Health Research Institute
• Investigators: Not Provided
• PRS Account: Bayer
• Verification Date: June 2022