Abelacimab vs. Rivaroxaban for Atrial Fibrillation

(AZALEA-TIMI 71 Trial)

Recruiting at 81 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

1287 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new blood thinner called abelacimab to see if it causes less bleeding compared to an existing drug, rivaroxaban. It focuses on patients with atrial fibrillation who are at a higher risk of stroke. Blood thinners help prevent strokes by stopping clots, but they can also cause bleeding.

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.

What data supports the effectiveness of the drug Rivaroxaban for atrial fibrillation?

Rivaroxaban has been shown to effectively reduce the risk of stroke and other blood clots in patients with atrial fibrillation, as demonstrated in clinical trials and real-world studies. ^{1 2 3 4 5}

Is Rivaroxaban safe for humans?

Rivaroxaban, a medication used to prevent blood clots, has been shown to be safe for humans, with a lower risk of causing bleeding in the brain compared to older treatments like warfarin. It is important for patients, especially older ones, to discuss their specific health conditions with their doctor to ensure it is a safe option for them. ^{1 2 6 7 8}

How does the drug Abelacimab differ from Rivaroxaban for atrial fibrillation?

Abelacimab is unique because it targets Factor XI, a different part of the blood clotting process, whereas Rivaroxaban targets Factor Xa. This difference in mechanism may offer an alternative for patients who need anticoagulation therapy. ^{1 9 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Abelacimab (MAA868) Experimental Treatment 1 Intervention

Treatment group 1: Abelacimab middle dose subcutaneous (s.c.) monthly Treatment group 2: Abelacimab high dose subcutaneous (s.c.) monthly Extension Treatment Group: Abelacimab high dose subcutaneous (s.c.) monthly

Group II: 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+

Laboratory Corporation of America

Industry Sponsor

Trials

32

Recruited

18,800+

The TIMI Study Group

Collaborator

Trials

22

Recruited

129,000+

Findings from Research

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Comparative analysis and meta-analysis of major clinical trials with oral factor Xa inhibitors versus warfarin in atrial fibrillation. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Present profiles of novel anticoagulant use in Japanese patients with atrial fibrillation: insights from the Rivaroxaban Postmarketing Surveillance Registry. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. [2022]

4. Netherlands 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Real-world comparative effectiveness and safety of rivaroxaban and warfarin in nonvalvular atrial fibrillation patients. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of apixaban in the patients undergoing the ablation of atrial fibrillation. [2015]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Rivaroxaban - Metabolism, Pharmacologic Properties and Drug Interactions. [2018]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical utility of rivaroxaban in stroke prevention associated with nonvalvular atrial fibrillation - patient considerations. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Population model of the pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct factor xa inhibitor--in healthy subjects. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of rivaroxaban in the treatment of nonvalvular atrial fibrillation. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. [2022]

12. New Zealand 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. [2021]