Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation (ROXI-ATLAS)

A Phase 2, Randomized, Multicenter, Open-label, Blinded-endpoint Study to Evaluate the Safety of REGN7508 and REGN9933, Monoclonal Antibodies Against FXI, Versus Apixaban in Participants With Atrial Fibrillation (ROXI-ATLAS)

This study is researching experimental drugs called REGN7508 and REGN9933. The study is focused on participants who have atrial fibrillation, which means that the heart beats too fast and unevenly. REGN7508 and REGN9933 are designed to help stop blood clots forming in patients with atrial fibrillation.

The aim of the study is to see how well REGN7508 and REGN9933 work in patients that get medicine for their atrial fibrillation. The bleeding effects of REGN7508 and REGN9933 will be compared to another medicine (apixaban), which is available on the market to treat and prevent formation of blood clots.

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

• What side effects may happen from taking REGN7508 or REGN9933
• How well do the study drugs reduce the risk of having a stroke
• How much of REGN7508 or REGN9933 is in the blood at different times
• Whether the body makes antibodies against REGN7508 or REGN9933 (which could make the drugs less effective or could lead to side effects)

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation (AF)
• Intervention / Treatment: Drug: REGN7508; Drug: Apixaban; Drug: REGN9933

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Phase 2

Contacts and Locations

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

Study Locations

• Canada
  • Québec, Canada, G1R 2J6
    • Recruiting
    • CHU de Quebec-Universite Laval
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2G3
      • Recruiting
      • University of Alberta Hospital - Cardiology
  • British Columbia
    • Victoria, British Columbia, Canada, V8Z 0B9
      • Recruiting
      • Victoria Cardiac Arrhythmia Trials
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1G-1A7
      • Recruiting
      • GA Research Associates Ltd.
  • Ontario
    • Greater Sudbury, Ontario, Canada, P3E 5J1
      • Recruiting
      • Health sciences North - Cardiology
    • Oshawa, Ontario, Canada, L1J 2K1
      • Recruiting
      • Dr James Cha
    • Scarborough Village, Ontario, Canada, M1B 4Z8
      • Recruiting
      • Heart Health Institute Research Inc. - Cardiology
  • Quebec
    • Longueuil, Quebec, Canada, J4H 4B9
      • Recruiting
      • Viacar Recherches Cliniques Inc. - Cardiologie
    • Sherbrooke, Quebec, Canada, J1LOK3
      • Recruiting
      • Diex Recherche Inc.
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Recruiting
      • Centre Hospitalier Universitaire De Sherbrooke (CHUS) - Cardiologie
    • Trois-Rivières, Quebec, Canada, G9A 4P3
      • Recruiting
      • Diex Recherche Trois-rivieres
• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • Recruiting
      • SEC Clinical Research
    • Fairhope, Alabama, United States, 36532
      • Recruiting
      • Eastern Shore Research Institute
  • California
    • Encinitas, California, United States, 92024
      • Recruiting
      • North Coast Cardiology
    • Fremont, California, United States, 94538
      • Recruiting
      • Mission Cardiovascular Research Institute
    • Huntington Beach, California, United States, 92648
      • Recruiting
      • National Institute of California Heart and Vein Specialists
    • Pasadena, California, United States, 91105
      • Recruiting
      • Profound Research LLC at Southern California Heart Specialists
    • Pomona, California, United States, 91767
      • Recruiting
      • Empire Clinical Research
    • Santa Rosa, California, United States, 95405
      • Recruiting
      • Northbay Clinical Research Center
    • Ventura, California, United States, 93003
      • Recruiting
      • Cardiology Associates Medical Group
    • West Hills, California, United States, 91307
      • Recruiting
      • Interventional Cardiology Medical Group
  • Florida
    • Cutler Bay, Florida, United States, 33189
      • Recruiting
      • Nouvelle Clinical Research LLC
    • Miami Lakes, Florida, United States, 33014
      • Recruiting
      • Inpatient Research Clinic LLC
    • Sarasota, Florida, United States, 34239
      • Recruiting
      • Cardiovascular Center of Sarasota Foundation for Research and Education
    • Winter Park, Florida, United States, 32789
      • Recruiting
      • Clinical Site Partners, LLC dba Flourish Research
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Health Sciences Research Building II
    • Johns Creek, Georgia, United States, 30024
      • Recruiting
      • NSC Research, Inc
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University
    • Indianapolis, Indiana, United States, 46237
      • Recruiting
      • Blue Coast Research Center, LLC
    • Indianapolis, Indiana, United States, 46237
      • Recruiting
      • Franciscan Physician Network, Indiana Heart Physicians
    • Merrillville, Indiana, United States, 46410
      • Recruiting
      • Indiana Medical Research
    • Richmond, Indiana, United States, 47374
      • Recruiting
      • Reid Physician Associates
  • Louisiana
    • West Monroe, Louisiana, United States, 71291
      • Recruiting
      • Monroe Research, LLC
  • Maryland
    • Ft. Washington, Maryland, United States, 20744
      • Recruiting
      • Anderson Medical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Lahey Health, Beth Israel Deaconess Medical Center (BIDMC)
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Recruiting
      • Profound Research, Millennium Cardiology
    • Flint, Michigan, United States, 48504
      • Recruiting
      • AA Medical Research Center (MRC)
  • Minnesota
    • Maplewood, Minnesota, United States, 55109
      • Recruiting
      • Fairview Health Services
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
      • Recruiting
      • Moses Cone Hospital Operating Corporation dba Cone Health, Lebauer-Brodie Center for Cardiovascular Research
  • Ohio
    • Marion, Ohio, United States, 43302
      • Recruiting
      • K&R Research LLC
    • Maumee, Ohio, United States, 43537
      • Recruiting
      • Advanced Medical Research
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Recruiting
      • Monument Health Clinical Research
  • Tennessee
    • Jefferson City, Tennessee, United States, 37760
      • Recruiting
      • East Coast Institute for Research, Jefferson City
  • Texas
    • Amarillo, Texas, United States, 79106
      • Recruiting
      • PharmaTex Research
    • McKinney, Texas, United States, 75071
      • Recruiting
      • Complete Heart Care P.A.
    • Odessa, Texas, United States, 79761
      • Recruiting
      • Permian Research Foundation
    • Tyler, Texas, United States, 75701
      • Recruiting
      • Tyler Cardiovascular Consultants
  • Utah
    • Clinton, Utah, United States, 84015
      • Recruiting
      • Alpine Research TC

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 felt 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 Thromboembolism (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 Normalization 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 successful ablation therapy or Left Atrial Appendage (LAA) occlusion/exclusion, or planned ablation or LAA occlusion/exclusion as described in the protocol
4. Had an ischemic stroke within 2 days prior to randomization
5. Has estimated Glomerular Filtration Rate (eGFR) <15 mL/min/1.73m^2 within 30 days prior to randomization or on dialysis or expected to be started as described in the protocol
6. Has a history of central nervous system bleeding within 30 days prior to 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: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Apixaban	Drug: Apixaban; Administered per the protocol; Other Names: Eliquis
Experimental: REGN7508	Drug: REGN7508; Administered per the protocol; Other Names: cenvacibart
Experimental: REGN9933	Drug: REGN9933; Administered per the protocol; Other Names: amrecibart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of any bleeding	Defined as the composite of International Society on Thrombosis and Haemostasis (ISTH) major bleeding, ISTH Clinically Relevant Non-Major (CRNM) bleeding, or minor bleeding	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of the composite of ISTH major bleeding or ISTH CRNM bleeding	12 weeks
Incidence of ISTH major bleeding	12 weeks
Incidence of ISTH CRNM bleeding	12 weeks
Incidence of minor bleeding	12 weeks
Number of ISTH major bleeding events	12 weeks
Number of ISTH CRNM bleeding events	12 weeks
Number of minor bleeding events	12 weeks
Incidence of Treatment-Emergent Adverse Events (TEAEs)	Approximately 25 weeks
Severity of TEAEs	Approximately 25 weeks
Incidence of the composite of stroke or systemic embolism	Approximately 12 weeks
Incidence of Antidrug Antibodies (ADA) to REGN7508	12 weeks
Magnitude of ADA to REGN7508	12 weeks
Incidence of ADA to REGN9933	12 weeks
Magnitude of ADA to REGN9933	12 weeks
Concentrations of REGN7508	Approximately 25 weeks
Concentrations of REGN9933	Approximately 25 weeks
Change from baseline in activated Partial Thromboplastin Time (aPTT)	Approximately 25 weeks
Change from baseline in Prothrombin Time (PT)	Approximately 25 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2025
• Primary Completion (Estimated): February 9, 2027
• Study Completion (Estimated): April 21, 2027

Study Registration Dates

• First Submitted: September 9, 2025
• First Submitted That Met QC Criteria: September 9, 2025
• First Posted (Actual): September 16, 2025

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 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-2393

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