Abelacimab for Atrial Fibrillation

(LILAC-TIMI 76 Trial)

Recruiting at 634 trial locations

Overseen By Anthos Therapeutics

Age: 65+

Sex: Any

Trial Phase: Phase 3

Sponsor: Anthos Therapeutics, Inc.

Must not be taking: Vitamin K antagonists, DOACs

Disqualifiers: Acute reversible AF, Recent stroke, 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: Up to 30 months

1900 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests abelacimab, an anti-FXI antibody, to determine its effectiveness in preventing strokes or blood clots in individuals with atrial fibrillation (AF), a condition characterized by an irregular heartbeat. It targets those unable to take standard blood thinners due to risks or who prefer alternatives. Participants will receive either abelacimab or a placebo (a harmless pill resembling the real medicine) once a month. Ideal candidates have atrial fibrillation and face bleeding risks, such as frequent NSAID use or a history of falls. As a Phase 3 trial, this study marks 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 have been on certain blood thinners like warfarin or other similar drugs in the last 60 days, you may not be eligible to participate.

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

Research shows that abelacimab, the treatment under study, is generally well-tolerated by people with atrial fibrillation (AF). Studies have found that abelacimab causes fewer bleeding problems compared to another blood thinner, rivaroxaban. It significantly lowers the risk of major bleeding and other important bleeding issues, suggesting that abelacimab might be a safer choice for those who cannot use traditional oral blood thinners.

The evidence so far indicates that abelacimab is quite safe, with fewer bleeding-related side effects. This is important for patients with AF, as they often face such risks. For those considering joining a trial for abelacimab, current data suggests it is a promising and safe option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Atrial Fibrillation?

Unlike the standard treatments for atrial fibrillation, which often include blood thinners like warfarin or direct oral anticoagulants (DOACs), abelacimab offers a novel approach. Abelacimab is unique because it targets Factor XI, a specific protein in the blood clotting pathway, which could potentially reduce the risk of bleeding—a common concern with current options. Additionally, it is administered as a once-monthly subcutaneous injection, offering a more convenient and potentially more consistent therapeutic option compared to daily medications. Researchers are excited about abelacimab's potential to provide effective stroke prevention with fewer bleeding complications.

What evidence suggests that abelacimab might be an effective treatment for atrial fibrillation?

Research has shown that abelacimab, one of the treatments under study in this trial, can greatly reduce the risk of stroke in people with atrial fibrillation who cannot use regular blood thinners. Studies have found that abelacimab not only lowers the chance of stroke but also causes less bleeding compared to another common drug, rivaroxaban. In one study, abelacimab reduced the risk by about 7% to 8% per 100 patient-years, marking a significant improvement. This makes abelacimab a promising option for those needing an alternative to traditional blood thinners. Participants in this trial will be randomized to receive either abelacimab or a placebo. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with Atrial Fibrillation who can't take oral anticoagulants. Participants must be 65-74 years old with a high stroke risk score or at least 75 with a slightly lower score, and have at least one bleeding risk factor. People who've had recent serious bleeds or strokes, AF from reversible causes, or used certain blood thinners recently cannot join.

Inclusion Criteria

I have been diagnosed with Atrial Fibrillation or flutter confirmed by an ECG.

I or my doctor think blood thinners taken by mouth aren't right for me.

I am 65-74 with a high stroke risk score or 75+ with a moderate stroke risk score.

Exclusion Criteria

I have a mechanical heart valve or need one due to my valve disease.

My atrial fibrillation is due to a temporary cause like surgery or untreated thyroid issues.

I have not had a brain or eye bleed in the last 3 months or any brain bleed without blood thinner treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abelacimab 150 mg subcutaneous or matching placebo once monthly

Up to 30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abelacimab
• Placebo

Trial Overview The study tests abelacimab against a placebo to see if it lowers the chance of stroke or clots in patients unsuitable for standard blood thinner pills. It's designed to compare how well each treatment prevents these events without causing harmful side effects.

How Is the Trial Designed?

Group I: Abelacimab (MAA868) Experimental Treatment 1 Intervention

Patients will be randomized in a 1:1 ratio to receive abelacimab 150 mg subcutaneous (SC) or matching placebo once monthly.

Group II: Placebo Placebo Group 1 Intervention

Patients will be randomized in a 1:1 ratio to receive abelacimab 150 mg subcutaneous (SC) or matching placebo once monthly.

Who Is Running the Clinical Trial?

Anthos Therapeutics, Inc.

Lead Sponsor

Trials

6

Recruited

6,600+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a meta-analysis of 1691 patients undergoing atrial fibrillation ablation, apixaban showed similar rates of thromboembolic events and bleeding complications compared to warfarin, indicating its safety as an anticoagulant in this context.

The study found no deaths and low rates of major and minor bleeding events in patients treated with apixaban, supporting its use as a periprocedural anticoagulation option during AF ablation procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban for periprocedural anticoagulation during catheter ablation of atrial fibrillation: a systematic review and meta-analysis of 1691 patients. Blandino, A., Bianchi, F., Biondi-Zoccai, G., et al.[2018]

In a study of 342 patients undergoing catheter ablation for atrial fibrillation, apixaban was found to be as effective and safe as warfarin for periprocedural anticoagulation, with no significant differences in bleeding or thromboembolic complications between the two groups.

The rates of major and minor bleeding complications were similar for both apixaban (1% major, 4% minor) and warfarin (1% major, 5% minor), indicating that apixaban is a viable alternative to warfarin in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of apixaban in the patients undergoing the ablation of atrial fibrillation. Nagao, T., Inden, Y., Shimano, M., et al.[2015]

Direct oral anticoagulants (DOACs) are not recommended for patients with valvular atrial fibrillation (AF) associated with moderate-to-severe mitral stenosis or mechanical heart valves, as landmark trials excluded these populations.

For patients with valvular AF due to moderate-to-severe mitral stenosis or mechanical heart valves, dose-adjusted warfarin remains the preferred anticoagulant, while DOACs may be suitable for those with mild mitral stenosis or bioprosthetic valves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can Direct Oral Anticoagulants Be Used for Stroke Prevention Among Patients with Valvular Atrial Fibrillation? Anderson, SL., Marrs, JC.[2020]

In a study of 94 patients with nonvalvular atrial fibrillation (NVAF) taking rivaroxaban, peak anti-Xa activity (AXA) levels were significantly higher than trough levels, indicating that drug concentration varies throughout the dosing period.

The study found that higher peak AXA levels were independently associated with an increased risk of bleeding events, with 23.4% of patients experiencing major bleeding, suggesting that monitoring AXA levels could help predict and manage bleeding risks in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring of anti-Xa activity and factors related to bleeding events: A study in Japanese patients with nonvalvular atrial fibrillation receiving rivaroxaban. Sakaguchi, T., Osanai, H., Murase, Y., et al.[2022]

ONO-7684, a novel oral factor XI inhibitor, was well tolerated in healthy subjects across various doses, with a low incidence of adverse events and no evidence of increased bleeding risk.

The drug effectively inhibited factor XI activity and supported once-daily dosing due to its favorable pharmacokinetics, with a half-life ranging from 16.0 to 27.9 hours depending on the feeding state.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ONO-7684 a novel oral FXIa inhibitor: Safety, tolerability, pharmacokinetics and pharmacodynamics in a first-in-human study. Beale, D., Dennison, J., Boyce, M., et al.[2021]

The study involved 271 patients taking either rivaroxaban or dabigatran and found that anti-FXa-IIa activity detection is a reliable method for pharmacodynamic evaluation in the Asian population.

However, the study revealed that there was no significant correlation between drug adherence and anti-FXa-IIa activity, suggesting that while the test is useful for measuring drug effects, it may not effectively evaluate patient adherence to direct oral anticoagulants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-FXa-IIa activity test in Asian and its potential role for drug adherence evaluation in patients with direct oral anticoagulants: a nationwide multi-center synchronization study. Liu, Z., Xie, Q., Xiang, Q., et al.[2022]

In a review of 11 randomized controlled trials involving 59,164 patients with non-valvular atrial fibrillation, factor-Xa inhibitors (FXIs) showed a significant reduction in the risk of stroke and systemic embolic events compared to Vitamin K antagonists (VKAs).

FXIs also significantly reduced major bleeding events and all-cause mortality without increasing the risk of stroke, indicating they may be a safer and more effective alternative to VKAs for patients with NVAF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of oral factor-Xa inhibitors versus Vitamin K antagonist in patients with non-valvular atrial fibrillation: Meta-analysis of phase II and III randomized controlled trials. Garg, J., Chaudhary, R., Krishnamoorthy, P., et al.[2017]

Abelacimab, a novel monoclonal antibody targeting Factor XI, demonstrated significant reductions in free FXI levels (over 99%) after intravenous administration, indicating its strong anticoagulant effect.

The drug was found to be safe and well-tolerated in both healthy volunteers and patients with atrial fibrillation, with no clinically relevant bleeding events reported, supporting its potential for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of Abelacimab (MAA868), a novel dual inhibitor of Factor XI and Factor XIa. Yi, BA., Freedholm, D., Widener, N., et al.[2023]

In patients with renal impairment (RI), rivaroxaban and edoxaban showed higher anti-factor Xa activity (AXA) values in those with severe RI compared to moderate RI, indicating a potential need for careful monitoring in these patients.

Apixaban, however, did not show significant differences in AXA values between moderate and severe RI patients, and it had the lowest peak-to-trough ratio of AXA values among the three factor-Xa inhibitors, suggesting it may have a more stable pharmacokinetic profile in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Anti-factor Xa Activity Among Three Different Factor Xa Inhibitors in Non-valvular Atrial Fibrillation Patients with Renal Impairment. Tobe, A., Osanai, H., Tanaka, A., et al.[2021]

Citations

1. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2406674

Abelacimab versus Rivaroxaban in Patients with Atrial ... Among patients with atrial fibrillation who were at moderate-to-high risk for stroke, treatment with abelacimab resulted in markedly lower ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40546068/

A Prespecified Analysis of the AZALEA-TIMI 71 Trial The novel factor XI inhibitor abelacimab significantly reduced the risk of bleeding compared with rivaroxaban in patients with atrial fibrillation.

3. ahajournals.org ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.125.075816?doi=10.1161/CIRCULATIONAHA.125.075816

Abelacimab Versus Rivaroxaban in Patients With Atrial ... As a result, the absolute risk reductions achieved with abelacimab were greater in this subgroup—≈7% to 8% per 100 patient-years. This indicates ...

4. thecardiologyadvisor.com thecardiologyadvisor.com/news/kidney-function-abelacimab-bleeding-risk-atrial-fibrilation-treatment/

Abelacimab Reduces Bleeding Risk in Atrial Fibrillation ... According to Dr Patel's team, “abelacimab consistently reduced the risk of bleeding compared with rivaroxaban across a range of kidney function ...

5. anthostherapeutics.com anthostherapeutics.com/press-release/anthos_2024-08-15_release-16/

First-Ever Cost-Effectiveness Analysis of a Factor XI ... The analysis indicates that abelacimab could offer a potential cost-savings of $50,000 USD and improvements of 1.5 quality-adjusted life years ( ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39842011/

Abelacimab versus Rivaroxaban in Patients with Atrial ... Treatment with abelacimab resulted in markedly lower levels of free factor XI and fewer bleeding events than treatment with rivaroxaban.

7. jamanetwork.com jamanetwork.com/journals/jamacardiology/fullarticle/2838520?widget=personalizedcontent&previousarticle=192996

Safety of Factor XI Inhibition With Abelacimab in Atrial ... Abelacimab is an FXI inhibitor that significantly reduced the risk of major and clinically relevant nonmajor (CRNM) bleeding vs rivaroxaban in ...