Milvexian for Acute Coronary Syndrome

(LIBREXIA-ACS Trial)

Recruiting at 1271 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must not be taking: Anticoagulants

Disqualifiers: Type 2 MI, Planned CABG, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to 3 years 6 months

16000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether milvexian, an experimental drug, can reduce major heart-related problems like heart attacks and strokes more effectively than a placebo when added to standard treatment. It targets individuals who have recently experienced acute coronary syndrome (ACS), including heart attacks or severe chest pain due to heart issues. Eligible participants should have experienced ACS within the past week and possess certain risk factors such as diabetes or a history of heart problems. The trial will compare milvexian with a placebo, both taken alongside usual heart medications. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic anticoagulation therapy, you may not be eligible to participate.

Is there any evidence suggesting that milvexian is likely to be safe for humans?

Research shows that milvexian, a treatment under study for acute coronary syndrome, is generally well-tolerated. Studies have found that milvexian blocks a protein called Factor XIa, reducing blood clots with a low risk of bleeding, which indicates good safety.

Previous studies have examined milvexian's safety and tolerability in people, finding that most did not experience serious side effects. However, like any medication, some side effects can occur. Therefore, participants must be closely monitored during the trial.

Overall, evidence supports milvexian's safety for further testing in patients with acute coronary syndrome. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about milvexian for acute coronary syndrome because it represents a novel approach compared to standard treatments like antiplatelet drugs and anticoagulants. Unlike traditional therapies that primarily target platelets or clotting factors, milvexian is an oral, small-molecule inhibitor that specifically targets Factor XIa, a key enzyme in the blood clotting process. This targeted action means it has the potential to reduce the risk of bleeding, a common side effect associated with existing anticoagulants, while still effectively preventing harmful clots. This unique mechanism of action could offer a safer and more effective option for patients recovering from acute coronary syndrome.

What evidence suggests that milvexian might be an effective treatment for acute coronary syndrome?

Research shows that milvexian, which participants in this trial may receive, may help lower the risk of serious heart problems, such as heart attacks and strokes. Milvexian blocks a part of the blood clotting process, potentially reducing the chance of clots forming with less risk of bleeding. Previous studies suggest that this method can improve health outcomes for patients who have recently experienced acute coronary syndrome (ACS), a condition where blood flow to the heart is suddenly reduced. This treatment could be a promising option for managing heart health after such events. ^{1 2 3 4 5}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults who recently had a heart-related emergency (acute coronary syndrome) with certain risk factors like being over 65, diabetes, or past heart issues. They must not need chronic blood thinners and should have no major bleeding risks or planned heart surgeries after joining the study.

Inclusion Criteria

I am not pregnant, breastfeeding, nor planning to become pregnant soon after the study ends.

I am 65 or older, have diabetes, or have a history of heart issues.

I had symptoms of a heart attack and confirmed heart damage within the last week.

Exclusion Criteria

I haven't had significant bleeding or a bleeding disorder in the last 3 months.

I am scheduled for heart bypass surgery or a procedure to open my heart's arteries.

I am on long-term blood thinners as advised by my doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive either milvexian or placebo, in addition to standard-of-care, to evaluate the reduction in risk of major adverse cardiovascular events

Up to 3 years 6 months

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Milvexian
• Placebo

Trial Overview The study tests if Milvexian can better prevent serious heart problems when added to usual treatments compared to a placebo. It focuses on avoiding events like death from heart causes, new heart attacks, and strokes in patients who've just had one such event.

How Is the Trial Designed?

Group I: Milvexian Experimental Treatment 1 Intervention

Participants enrolled within 7 days of an acute coronary syndrome (ACS), who have undergone cardiac catheterization with percutaneous intervention (PCI) or who are being managed conservatively with or without catheterization, and who are receiving antiplatelet therapy standard-of-care (single antiplatelet therapy \[SAPT\] or dual antiplatelet therapy \[DAPT\]) as determined by the investigator will receive milvexian 25 milligrams (mg), orally, twice daily.

Group II: Placebo Placebo Group 1 Intervention

Participants enrolled within 7 days of an ACS, who have undergone cardiac catheterization with PCI or who are being managed conservatively with or without catheterization, and who are receiving antiplatelet therapy standard-of-care (SAPT or DAPT) as determined by the investigator will receive placebo orally, twice daily.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a comprehensive review of 54 phase-I studies involving 1015 healthy volunteers over 10 years, the overall incidence of adverse events was found to be 12.8%, with a higher rate for active drugs (13.7%) compared to placebo (7.9%).

Most adverse events were minor, with only 3% classified as severe, and no deaths or life-threatening events reported, highlighting that while adverse events are common in phase-I trials, they are typically not serious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. Sibille, M., Deigat, N., Janin, A., et al.[2019]

In a review of 109 clinical studies with 1228 healthy volunteers, 19% reported adverse events during placebo administration, highlighting that even without active treatment, participants can experience side effects.

Adverse events were more common with repeated dosing (28%) and among elderly participants (26%), with headaches, drowsiness, and asthenia being the most frequently reported issues, indicating that placebo effects can significantly influence safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Rosenzweig, P., Brohier, S., Zipfel, A.[2023]

In a review of 24 Phase I studies involving 430 healthy male volunteers over 5 years, the overall incidence of adverse events was 13.5%, with a higher rate for active drug treatments (15.3%) compared to placebo (7.4%).

Severe adverse events occurred in 20 cases (0.36%), but there were no deaths or life-threatening incidents, indicating that while adverse events are common, they are generally not severe in Phase I trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase one studies: a study in 430 healthy volunteers. Sibille, M., Deigat, N., Olagnier, V., et al.[2019]

EudraVigilance, the European pharmacovigilance database, has been crucial for monitoring the safety of medicines since its launch in 2001, with 50% of scientific publications using its data to describe safety issues.

Recent enhancements to EudraVigilance, including broader access to data and improved functionalities, aim to facilitate better safety monitoring and support health research, ultimately promoting the safe and effective use of medicines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EudraVigilance Medicines Safety Database: Publicly Accessible Data for Research and Public Health Protection. Postigo, R., Brosch, S., Slattery, J., et al.[2021]

A multicenter study involving 300 patients demonstrated that an active pharmacovigilance model, using structured phone interviews, effectively identified a higher incidence of severe hemorrhage in patients using acetylsalicylic acid (ASA) compared to those using other non-ASA NSAIDs, highlighting a specific risk associated with this subclass.

The study suggests that this active pharmacovigilance approach can uncover hidden adverse drug reactions (ADRs) that may not be evident in traditional methods, making it a valuable tool for monitoring the safety of widely used medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new model of pharmacovigilance? A pilot study. Zancan, A., Locatelli, C., Ramella, F., et al.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39986336/

Oral factor xia inhibitor milvexian after a recent acute ... Factor XIa inhibition reduces thrombin generation and may improve clinical outcomes with minimal bleeding risk. Design: Librexia ACS (ClinicalTrials.gov ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05754957

NCT05754957 | A Study of Milvexian in Participants After ... The purpose of this study is to evaluate that milvexian is superior to placebo, in addition to standard-of-care, in reducing the risk of major adverse ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8841437/

First‐in‐human study of milvexian, an oral, direct, small ... This study evaluated the safety/tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of the selective, direct, small molecule FXIa inhibitor ...

4. news.bms.com news.bms.com/news/details/2023/Milvexian-Granted-U.S.-FDA-Fast-Track-Designation-for-All-Three-Indications-Under-Evaluation-in-Phase-3-Librexia-Program-Ischemic-Stroke-Acute-Coronary-Syndrome-and-Atrial-Fibrillation/default.aspx

Milvexian Granted U.S. FDA Fast Track Designation for All ... Librexia ACS is a randomized, double-blind, placebo-controlled, event-driven study to demonstrate the efficacy and safety of milvexian after a ...

5. thecardiologyadvisor.com thecardiologyadvisor.com/news/clinical-trial-milvexian-after-recent-acute-coronary-syndrome-librexia-acs/

Clinical Trial: Milvexian After Recent Acute Coronary ... Primary Outcomes. The primary outcome is measuring the time to first occurrence of a MACE event including CV death, MI, and ischemic stroke.