Safety and Tolerability of Abelacimab (MAA868) vs. Rivaroxaban in Patients With Atrial Fibrillation

Study Overview
=================
Brief Summary
-----------------
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 moderate-to-high risk of stroke.

Official Title
-----------------
A Multicenter, RandomiZed, Active-ControLled Study to Evaluate the Safety and Tolerability of Two Blinded Doses of Abelacimab (MAA868) Compared With Open-Label Rivaroxaban in Patients With Atrial Fibrillation (AZALEA)

Conditions
-----------------
Atrial Fibrillation (AF), Stroke

Intervention / Treatment
-----------------
* Biological: Abelacimab
* Drug: Rivaroxaban


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female patients ≥ 55 years old Patients with a history of atrial fibrillation (AF) or atrial flutter with planned indefinite anticoagulation Patients with a CHA2DS2-VASc of ≥4 OR a CHA2DS2-VASc of ≥3 with at least 1 of the following: Planned concomitant use of antiplatelet medication use (i.e., aspirin and/or P2Y12 inhibitor) for the duration of the trial Creatinine Clearance (CrCl) ≤50 ml/min by the Cockcroft-Gault equation Exclusion Criteria: History of hypersensitivity to any of the study drugs (including rivaroxaban) or its excipients, to drugs of similar chemical classes, or any contraindication listed in the label for rivaroxaban Patients with an intracranial or intraocular bleed within the 3 months prior to screening Clinically significant mitral stenosis (valve area <1.5 cm2) Mechanical heart valve or other indication for anticoagulation therapy other than atrial fibrillation (e.g., venous thromboembolism) Known presence of an atrial myxoma or left ventricular thrombus History of left atrial appendage closure or removal Active endocarditis Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is an event-driven, randomized, active-controlled, blinded endpoint, parallel-group study to evaluate the effect of two blinded doses of abelacimab relative to open-label rivaroxaban on the rate of major or clinically relevant non-major (CRNM) bleeding events in patients with atrial fibrillation (AF) who are at moderate-to-high risk of stroke.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abelacimab (MAA868)<br>Treatment group 1: Abelacimab middle dose subcutaneous (s.c.) monthly Treatment group 2: Abelacimab high dose subcutaneous (s.c.) monthly | Biological: Abelacimab<br>* Abelacimab provided as liquid in vial (150 mg/mL)<br>* Other names: MAA868;|
| Active Comparator: Rivaroxaban<br>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. | Drug: Rivaroxaban<br>* Rivaroxaban 15 mg and 20 mg provided as commercially available film-coated tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate effect of abelacimab relative to rivaroxaban on the rate of major or clinically relevant non-major (CRNM) bleeding events | Time to first event of composite of International Society on Thrombosis and Haemostasis (ISTH)-defined major bleeding or CRNM bleeding events | From randomization through study completion, an average of 17 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate effect of abelacimab relative to rivaroxaban on the rate of major bleeding events | Time to first event ISTH-defined major bleeding events | From randomization through study completion, an average of 17 months | 
| Evaluate the effect of abelacimab relative to rivaroxaban on the rate of major or minor bleeding events | Time to first event ISTH-defined major or minor bleeding events | From randomization through study completion, an average of 17 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
randomized, prospective, blinded endpoint evaluation, abelacimab, MAA868, rivaroxaban, atrial fibrillation, Factor XI, stroke, bleeding events, anti-coagulant, anticoagulation therapy