Milvexian for Stroke

(LIBREXIA-STROK Trial)

Recruiting at 1138 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: Antiplatelets

Disqualifiers: Intracranial hemorrhage, Cardio-embolic stroke, Bleeding risk, Active liver disease, 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: Unknown

Duration: 90 days

15000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether milvexian can reduce the risk of another stroke in individuals who recently had an ischemic stroke (caused by a blood clot) or a high-risk transient ischemic attack (a mini-stroke). Participants will receive either milvexian or a placebo (a harmless pill with no active medicine) while continuing standard antiplatelet therapy, which helps prevent blood clots. This trial suits those who have experienced an acute ischemic stroke or high-risk transient ischemic attack and are already on antiplatelet treatment. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that current or planned antiplatelet treatment is allowed. If you are taking acetyl salicylic acid (ASA), it should be limited to a low dose of 75 to 100 mg per day.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that milvexian has been tested for safety in people who experienced a sudden stroke due to a blocked blood vessel. Previous studies indicate that when combined with standard medication that prevents blood cells from clumping, milvexian does not significantly increase serious side effects, suggesting the treatment is generally well-tolerated.

The FDA granted milvexian "Fast Track" status, highlighting its potential importance and the need for quick development. This designation suggests that early data, including safety information, might be promising. However, like any new treatment, milvexian's safety continues to be carefully monitored in ongoing studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Milvexian is unique because it targets Factor XIa, a key player in the blood clotting process, which sets it apart from standard treatments like aspirin or clopidogrel that focus on platelet inhibition. This different mechanism may lead to fewer bleeding complications, a common concern with current therapies. Researchers are excited about milvexian's potential to effectively prevent strokes with possibly improved safety compared to existing options.

What evidence suggests that milvexian might be an effective treatment for stroke?

Research shows that milvexian, which participants in this trial may receive, can help lower the risk of another ischemic stroke. It blocks a specific part of the blood clotting process, preventing dangerous clots while minimizing bleeding risk. The FDA granted milvexian Fast Track status due to its potential to treat conditions like ischemic stroke, reflecting confidence in its promise based on early research findings. ^{1 5 6 7 8}

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've recently had a mild ischemic stroke or high-risk TIA, with specific criteria like NIHSS score <=7 and an ABCD2 Score >=6. They must be able to take low-dose antiplatelet medication and not be at risk of pregnancy. Exclusions include prior serious brain bleeds, strokes from heart problems needing blood thinners, other non-athero-thrombotic causes, bleeding risks, liver disease, or allergies to the study drug.

Inclusion Criteria

I had a stroke or TIA with specific conditions met.

Willing and able to adhere to the lifestyle restrictions specified in this protocol

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

Exclusion Criteria

My stroke or TIA was caused by a reason other than blood clot issues.

I had a brain bleed over a year ago and received proper treatment for it.

My stroke or TIA was caused by a clot from the heart, and I need blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive milvexian or placebo orally twice daily after an acute ischemic stroke or high-risk transient ischemic attack

90 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

41 months

What Are the Treatments Tested in This Trial?

Interventions

• Milvexian
• Placebo

Trial Overview The LIBREXIA-STROKE trial is testing if Milvexian can prevent another stroke better than a placebo (a dummy pill). Participants are chosen randomly to receive either Milvexian or placebo within 48 hours after their initial stroke or TIA symptoms start.

How Is the Trial Designed?

Group I: Milvexian Experimental Treatment 1 Intervention

Participants after an acute ischemic stroke or high-risk transient ischemic attack (TIA) who are receiving antiplatelet therapy standard-of-care (SAPT \[single antiplatelet therapy\] or DAPT \[dual antiplatelet therapy\]) will receive milvexian 25 milligrams (mg), orally, twice daily.

Group II: Placebo Placebo Group 1 Intervention

Participants after an acute ischemic stroke or high-risk TIA who are receiving antiplatelet therapy standard-of-care (SAPT or DAPT) 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 Company (BMS)

Collaborator

Trials

2

Recruited

15,000+

Published Research Related to This Trial

In a multicenter, randomized, placebo-controlled study involving 252 acute ischemic stroke patients, edaravone showed a significant improvement in functional outcomes compared to placebo, as measured by the modified Rankin Scale (p = 0.0382).

Edaravone acts as a neuroprotective agent by inhibiting vascular endothelial cell injury and reducing neuronal damage, suggesting its potential as an effective treatment for acute ischemic stroke when administered within 72 hours of onset.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. [2022]

The combination of atomoxetine and intensive speech therapy was safe and feasible for four adult patients with post-stroke aphasia, with no adverse effects reported during the study.

All patients showed improvements in language function, with significant increases in scores on language assessments and enhanced cortical blood flow in areas surrounding the brain lesions, indicating potential therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atomoxetine administration combined with intensive speech therapy for post-stroke aphasia: evaluation by a novel SPECT method. Yamada, N., Kakuda, W., Yamamoto, K., et al.[2019]

Dengzhanhua injection demonstrated a significantly higher total effective rate (92.0%) compared to fufangdanshen injection (75.8%) in treating acute cerebral infarction among 100 patients, indicating its superior efficacy.

The treatment with dengzhanhua injection also led to significant improvements in hemorrheology and lipemia without any adverse reactions, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical curative effect of dengzhanhua injection on acute cerebral infarction: a report of 100 cases]. Zhang, SF., He, MD., Li, C.[2006]

Dalfampridine extended release (D-ER) was generally well tolerated in 83 participants with chronic post-ischemic stroke deficits, with no new safety concerns identified compared to previous trials.

The study found that D-ER significantly improved walking speed compared to placebo, indicating potential benefits for lower extremity sensorimotor function in stroke survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalfampridine in chronic sensorimotor deficits after ischemic stroke: A proof of concept study. Simpson, DM., Goldenberg, J., Kasner, S., et al.[2022]

Mexidol shows promise in post-stroke rehabilitation due to its broad effects on various disorders, particularly when used in long-term therapy to improve motor, cognitive, and emotional functions.

A tailored approach to rehabilitation, incorporating Mexidol and other treatments, is recommended to enhance patient outcomes, but further high-quality clinical studies are needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy in post-stroke rehabilitation]. Lyukmanov, RK., Rimkevichus, AA., Gnedovskaya, EV., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05702034

A Study of Milvexian in Participants After an Acute Ischemic ... The purpose of this study is to evaluate whether milvexian compared to placebo reduce the risk of recurrent ischemic stroke.

2. 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 ... Milvexian Granted U.S. FDA Fast Track Designation for All Three Indications Under Evaluation in Phase 3 Librexia Program: Ischemic Stroke, Acute ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT03766581

NCT03766581 | A Study on BMS-986177 for the ... The purpose of this clinical study is to determine whether the addition of an oral Factor XIa Inhibitor to Aspirin and Clopidogrel is more effective than ...

5. thecardiologyadvisor.com thecardiologyadvisor.com/news/clinical-trial-milvexian-after-acute-ischemic-stroke-or-high-risk-transient-ischemic-attack-librexia-strok/

Clinical Trial: Milvexian After Acute Ischemic Stroke or High ... A clinical trial, the LIBREXIA-STROK trial, is being conducted to determine the effect of milvexian therapy on stroke prevention.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38101902/

Safety and efficacy of factor XIa inhibition with milvexian for ... Factor XIa inhibition with milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischaemic stroke or ...

7. jnj.com jnj.com/media-center/press-releases/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

Milvexian Granted U.S. FDA Fast Track Designation for All ... Milvexian Granted U.S. FDA Fast Track Designation for All Three Indications Under Evaluation in Phase 3 Librexia Program: Ischemic Stroke, Acute ...

8. rush.edu rush.edu/clinical-trials/study-milvexian-participants-after-acute-ischemic-stroke-or-high-risk-transient

A Study of Milvexian in Participants after an Acute Ischemic ... The purpose of this study is to see if an experimental drug, called milvexian in addition to standard of care, is safe and useful in reducing the risk of future ...