Stroke and Systemic Embolism Prevention in Adult Participants With Atrial Fibrillation (ROXI-EVEREST)

A Phase 3, Randomized, Multicenter, Double-blind Study to Assess Stroke and Systemic Embolism Prevention With REGN7508, a Monoclonal Antibody Against Factor XI, Versus Apixaban in Participants With Atrial Fibrillation (ROXI-EVEREST)

This study is researching an experimental drug called REGN7508 (called "study drug") and how it compares against another treatment called apixaban. The study is focused on people who have atrial fibrillation, which means that the heart beats too fast and unevenly.

The aim of the study is to see how safe and effective REGN7508 is in preventing stroke and/or systemic embolism in participants with atrial fibrillation and how it compares against participants that will receive apixaban in this study.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drug
• Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects)

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation (AF)
• Intervention / Treatment: Drug: Placebo; Drug: REGN7508; Drug: Apixaban

• Study Type: Interventional
• Enrollment (Estimated): 15364
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGN7508 + Placebo	Drug: Placebo; Administered per the protocol; Drug: REGN7508; Administered per the protocol; Other Names: cenvacibart
Active Comparator: Apixaban + Placebo	Drug: Placebo; Administered per the protocol; Drug: Apixaban; Administered per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): September 11, 2029
• Study Completion (Estimated): December 10, 2029

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: May 29, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Stroke; Bleeding; Systemic embolism; Blood clots
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Embolism and Thrombosis; Pathological Conditions, Signs and Symptoms; Stroke; Thrombosis; Atrial Fibrillation; Hemorrhage; apixaban
• Other Study ID Numbers: R7508-CVA-24114; 2025-521617-97-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No