Stroke and Systemic Embolism Prevention in Adult Participants With Atrial Fibrillation

• REGN7508 (Drug), also known as cenvacibart: Administered per the protocol
• Apixaban (Drug): Administered per the protocol
• Placebo (Drug): Administered per the protocol

Primary outcomes

• Time to first occurrence of stroke (ischemic, hemorrhagic, or of unspecified type) or systemic embolism [Approximately 36 months]
• Time to first occurrence of International Society on Thrombosis and Haemostasis (ISTH) major bleeding or ISTH Clinically Relevant Non-Major (CRNM) bleeding [Approximately 36 months]

Secondary outcomes

• Time to first occurrence of stroke (ischemic, hemorrhagic, or of unspecified type), systemic embolism, ISTH major bleeding, or ISTH CRNM bleeding [Approximately 36 months]
• Time to first occurrence of stroke (ischemic, hemorrhagic, or of unspecified type), systemic embolism, or ISTH major bleeding [Approximately 36 months]
• Time to first occurrence of stroke (ischemic, hemorrhagic, or of unspecified type), systemic embolism, ISTH major bleeding, or all-cause death [Approximately 36 months]
• Time to first occurrence of ISTH major bleeding [Approximately 36 months]
• Time to first occurrence of hemorrhagic stroke, intracerebral hemorrhage, or hemorrhagic transformation of an ischemic stroke [Approximately 36 months]
• Time to occurrence of fatal bleeding [Approximately 36 months]
• Number of ISTH major bleeding events [Approximately 36 months]
• Number of ISTH CRNM bleeding events [Approximately 36 months]
• Number of minor bleeding events [Approximately 36 months]
• Time to all-cause death [Approximately 36 months]
• Occurrence of Treatment-Emergent Adverse Events (TEAEs) [Approximately 39 months]
• Severity of TEAEs [Approximately 39 months]
• Occurrence of Anti-Drug Antibodies (ADA) to REGN7508 [Approximately 36 months]
• Magnitude of ADA to REGN7508 [Approximately 36 months]

Sex: All, ages: 18 Years to any

Key Inclusion Criteria:

1. Has AF or flutter (paroxysmal or persistent), not considered to be secondary to a reversible cause, and an indication for indefinite anticoagulation treatment as described in the protocol
2. Meets one of the following:

   1. CHA2DS2-VA \[C: Congestive heart failure; H: Hypertension; A2: Age ≥75 years (double points); D: Diabetes mellitus; S2: Stroke or TIA or Systemic embolism (double points); V: Vascular disease; A: Age 65-74 years\] score ≥2 and Oral Anticoagulant (OAC) naïve OR
   2. CHA2DS2-VA score ≥3 OR
   3. CHA2DS2-VA score of 2 AND at least 1 enrichment criteria as described in the protocol
3. Must have an International Normalized Ratio (INR) <2.5 at the time of randomization if taking warfarin or another Vitamin K Antagonist (VKA)

Key Exclusion Criteria:

1. Has a mechanical heart valve prosthesis (Note: transcatheter aortic valve replacement is not an exclusion)
2. Has known moderate-to-severe mitral stenosis
3. Has had a successful ablation therapy without documented recurrent AF or a participant after Left Atrial Appendage (LAA) occlusion/exclusion or plan for ablation or LAA occlusion/exclusion within the next 6 months starting from randomization
4. Had an ischemic stroke within 2 days prior to randomization
5. Has persistent, uncontrolled hypertension (per investigator's discretion)
6. Has estimated Glomerular Filtration Rate (eGFR) <15 mL/min/1.73m2 within 30 days prior to randomization or is on dialysis or expected to be started on dialysis within the next 6 months starting from randomization

Note: Other protocol-defined Inclusion/ Exclusion criteria apply

• Clinical Trial Management, Study director, Regeneron Pharmaceuticals

NIH grants: 2025