Abelacimab vs. Rivaroxaban for Atrial Fibrillation

(AZALEA-TIMI 71 Trial)

Not currently recruiting at 93 trial locations

Overseen By Janeen Salter

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Anthos Therapeutics, Inc.

Must be taking: Anticoagulants

Must not be taking: Rivaroxaban

Disqualifiers: Intracranial bleed, Mechanical heart valve, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 17 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the bleeding risk of two treatments, abelacimab and rivaroxaban, for people with atrial fibrillation (AF), a heart condition that causes irregular and often rapid heartbeats. The researchers aim to determine which treatment is safer for those at moderate-to-high risk of stroke who require ongoing blood thinners. Participants receive either a low or high dose of abelacimab (an experimental treatment) or daily rivaroxaban. Suitable candidates have a history of atrial fibrillation or flutter and are already on anticoagulation therapy. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in AF treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it does require that you continue using antiplatelet medication like aspirin if it's already planned for you.

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

Research has shown that abelacimab, a new treatment for atrial fibrillation (AF), is generally safe. Studies have found that it significantly reduces the risk of bleeding compared to rivaroxaban, another AF treatment. Patients taking abelacimab experience fewer bleeding incidents, a common concern with blood thinners.

In earlier trials, abelacimab consistently led to fewer major bleeding problems and other significant bleeding events. These findings suggest that abelacimab might be a safer choice for those worried about bleeding risks with AF treatments.

While still under study, current evidence supports its safety. However, discussing options with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Abelacimab because it offers a novel approach to treating atrial fibrillation by targeting Factor XI, a key player in blood clot formation, while minimizing the risk of bleeding. Unlike standard treatments like Rivaroxaban, which directly inhibit Factor Xa, Abelacimab's unique mechanism may reduce the chance of dangerous side effects such as bleeding. Additionally, Abelacimab is administered as a monthly subcutaneous injection, which could improve convenience and adherence compared to daily oral medications. With these features, Abelacimab has the potential to become a safer and more convenient option for patients with atrial fibrillation.

What evidence suggests that this trial's treatments could be effective for atrial fibrillation?

This trial will compare Abelacimab with Rivaroxaban for patients with atrial fibrillation. Studies have shown that Abelacimab, a new treatment option in this trial, significantly reduces the risk of bleeding compared to Rivaroxaban. Research indicates that Abelacimab lowers levels of a protein called free factor XI, involved in blood clotting, leading to fewer bleeding events. In some patient groups, Abelacimab reduced bleeding risk by about 7% to 8% per 100 patient-years. This consistent reduction in bleeding risk appeared even in patients with varying kidney function levels. Overall, Abelacimab seems to be a promising option for reducing bleeding risks in patients with atrial fibrillation. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults aged 55 or older with atrial fibrillation at moderate-to-high stroke risk, who need long-term blood thinners. They should have a CHA2DS2-VASc score of ≥4, or ≥3 with certain conditions and planned use of antiplatelet meds. People can't join if they're allergic to the study drugs, had recent serious bleeding, significant heart valve narrowing, mechanical heart valves, other anticoagulant needs like clots, or specific heart conditions.

Inclusion Criteria

I am 55 years old or older.

You have a certain score on a risk assessment tool for stroke called CHA2DS2-VASc.

My kidney function, measured by creatinine clearance, is 50 ml/min or less.

Exclusion Criteria

I am on blood thinners for reasons other than atrial fibrillation.

I have a tumor in my heart's left chamber or a blood clot in my heart.

I have not had a brain or eye bleed in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either abelacimab or rivaroxaban to evaluate the bleeding profile in patients with atrial fibrillation

17 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants in the extension group continue to receive abelacimab high dose monthly

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Abelacimab
• Rivaroxaban

Trial Overview The ANT-006 study compares Abelacimab (MAA868) to Rivaroxaban in patients with atrial fibrillation to see which causes less bleeding. Patients are randomly assigned to receive either Abelacimab or Rivaroxaban as their anticoagulation therapy.

How Is the Trial Designed?

Group I: Abelacimab 90 mg (MAA868) Experimental Treatment 1 Intervention

Treatment group 1: Abelacimab low dose subcutaneous (s.c.) monthly Extension Treatment Group: Abelacimab high dose subcutaneous (s.c.) monthly

Group II: Abelacimab 150 mg (MAA868) Experimental Treatment 1 Intervention

Treatment group 2: Abelacimab high dose subcutaneous (s.c.) monthly Extension Treatment Group: Abelacimab high dose subcutaneous (s.c.) monthly

Group III: Rivaroxaban Active Control 1 Intervention

Treatment group 3: Rivaroxaban 20 mg by mouth; orally (p.o.) once per day with the evening meal Patients with a Creatinine Clearance (CrCl) ≤50 ml/min by the Cockcroft-Gault equation will have a dose adaptation to rivaroxaban 15 mg p.o. daily.

Who Is Running the Clinical Trial?

Anthos Therapeutics, Inc.

Lead Sponsor

Trials

6

Recruited

6,600+

Fortrea

Industry Sponsor

Trials

22

Recruited

5,800+

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

Laboratory Corporation of America

Industry Sponsor

Trials

32

Recruited

18,800+

The TIMI Study Group

Collaborator

Trials

22

Recruited

129,000+

Published Research Related to This Trial

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]

This study is evaluating the safety of rivaroxaban, an oral anticoagulant, compared to a vitamin K antagonist (VKA) in up to 250 patients with nonvalvular atrial fibrillation (NVAF) undergoing catheter ablation, focusing on major bleeding events within 30 days post-procedure.

The study aims to determine if rivaroxaban can be safely used without interruption during the ablation process, which could simplify anticoagulation management for patients compared to traditional VKAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of VENTURE-AF: a randomized, open-label, active-controlled multicenter study to evaluate the safety of rivaroxaban and vitamin K antagonists in subjects undergoing catheter ablation for atrial fibrillation. Naccarelli, GV., Cappato, R., Hohnloser, SH., et al.[2021]

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]

Rivaroxaban is effective in preventing stroke and systemic embolism in patients with nonvalvular atrial fibrillation, showing superiority over warfarin and similar efficacy to other direct oral anticoagulants like dabigatran, apixaban, and edoxaban.

However, rivaroxaban may carry a higher risk of bleeding compared to other DOACs, which is an important consideration for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of rivaroxaban in the treatment of nonvalvular atrial fibrillation. Norby, FL., Alonso, A.[2022]

Citations

1. 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.

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

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.

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. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.074037?doi=10.1161/CIRCULATIONAHA.125.074037

Abelacimab Versus Rivaroxaban in Patients With Atrial ... Inhibition of factor XI with abelacimab consistently reduced bleeding compared with rivaroxaban regardless of concomitant APT use, with greater ...

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

Safety of Factor XI Inhibition With Abelacimab in Atrial ... This secondary analysis of the AZALEA-TIMI 71 randomized clinical trial examines the safety of abelacimab vs rivaroxaban across a range of ...

8. ashpublications.org ashpublications.org/ashclinicalnews/news/8541/Abelacimab-Demonstrates-Safety-Superior-Bleeding

Abelacimab Demonstrates Safety, Superior Bleeding ... The study demonstrated that abelacimab significantly reduced major and clinically relevant non-major (CRNM) bleeding events compared with rivaroxaban.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04755283

NCT04755283 | Safety and Tolerability of Abelacimab ... The purpose of the ANT-006 study is to evaluate the bleeding profile of abelacimab relative to rivaroxaban in patients with atrial fibrillation (AF) at ...