Stroke and Systemic Embolism Prevention in Adult Participants With Atrial Fibrillation for Whom Oral Anticoagulation is Unsuitable (ROXI-INCLINE)

November 5, 2026 updated by: Regeneron Pharmaceuticals

A Master Protocol for a Phase 3, Randomized, Multicenter, Double-blind Study to Assess Stroke and Systemic Embolism Prevention With REGN7508 and REGN9933, Monoclonal Antibodies Against Factor XI, Versus Placebo in Participants With Atrial Fibrillation for Whom Oral Anticoagulation is Unsuitable (ROXI-INCLINE)

This study is researching 2 different experimental drugs called REGN7508 and REGN9933 (called "study drugs"). The study is focused on people who have atrial fibrillation, which means that the heart beats too fast and unevenly. When this happens, blood cannot move smoothly through the heart; it can slow down or pool in one spot, which can lead to the formation of blood clots.

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 effective and safe REGN7508 and REGN9933, individually, are in preventing ischemic stroke or systemic embolism in people with atrial fibrillation who cannot or may choose to not take blood thinners.

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

  • What side effects may happen from taking REGN7508 or REGN9933
  • How well does REGN7508 or REGN9933 lower the risk of having an ischemic stroke and/or systemic embolism compared to the placebo
  • How well does REGN7508 or REGN9933 lower the risk of having a major health problem affecting heart and blood circulation compared to placebo
  • How well does REGN7508 or REGN9933 lower the risk of death compared to placebo
  • How much REGN7508 or REGN9933 is in the blood at different times
  • Whether the body makes antibodies against REGN7508 or REGN9933 (which could make the study drugs less effective or could lead to side effects)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2628

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8L 5G4
        • Recruiting
        • Hamilton Medical Research Group (HMRG)
  • United States
    • Alabama
      • Dothan, Alabama, United States, 36305
        • Recruiting
        • SEC Clinical Research
    • Arizona
      • Glendale, Arizona, United States, 85351
        • Recruiting
        • Sun City Clinical Research
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Recruiting
        • Arkansas Cardiology P.A.
    • California
      • 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
      • La Jolla, California, United States, 92037
        • Recruiting
        • Profound Research LLC at San Diego Cardiovascular Associates
      • Northridge, California, United States, 91325
        • Recruiting
        • Valley Clinical Trials, LLC dba Flourish Research
      • Pasadena, California, United States, 91105
        • Recruiting
        • Profound Research LLC at Southern California Heart Specialists
      • Santa Maria, California, United States, 93454
        • Recruiting
        • FOMAT - Comprehensive Cardiovascular Care
      • Ventura, California, United States, 93003
        • Recruiting
        • Cardiology Associates Medical Group
      • West Hills, California, United States, 91307
        • Recruiting
        • Interventional Cardiology Medical Group
    • Florida
      • Jacksonville, Florida, United States, 32216
        • Recruiting
        • East Coast Institute for Research, Jacksonville
      • Medley, Florida, United States, 33166
        • Recruiting
        • South Florida Research Organization LLC
      • Pensacola, Florida, United States, 32503
        • Recruiting
        • Sec Clinical Research
      • 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, 30342
        • Recruiting
        • Atlanta Clinical Research Centers
      • Johns Creek, Georgia, United States, 30024
        • Recruiting
        • NSC Research, Inc
    • Indiana
      • Indianapolis, Indiana, United States, 46237
        • Recruiting
        • Franciscan Physician Network, Indiana Heart Physicians
      • Merrillville, Indiana, United States, 46410
        • Recruiting
        • Indiana Medical Research
      • Munster, Indiana, United States, 46321
        • Recruiting
        • Profound Research, Powers Health Medical Group - Electrophysiology
    • Louisiana
      • West Monroe, Louisiana, United States, 71291
        • Recruiting
        • Monroe Research, LLC
    • Michigan
      • Bloomfield Hills, Michigan, United States, 48304
        • Recruiting
        • Profound Research, Cardiology and Vascular Associates (CAVA) - Bloomfield Hills
      • Farmington Hills, Michigan, United States, 48334
        • Recruiting
        • Profound Research, Millennium Cardiology
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Flint Clinical Research
      • Flint, Michigan, United States, 48504
        • Recruiting
        • AA Medical Research Center (MRC)
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • Recruiting
        • Jackson Heart Clinic
      • Olive Branch, Mississippi, United States, 38654
        • Recruiting
        • Olive Branch Family Medical Center
    • New York
      • Staten Island, New York, United States, 10309
        • Recruiting
        • Super Health Pharmacy
    • North Carolina
      • Concord, North Carolina, United States, 28025
        • Recruiting
        • Hawthorne Health, Moose Pharmacy of Concord
    • Ohio
      • Marion, Ohio, United States, 43302
        • Recruiting
        • K&R Research LLC
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • Recruiting
        • AnMed Health
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Recruiting
        • Monument Health Clinical Research
    • Tennessee
      • Tullahoma, Tennessee, United States, 37388
        • Recruiting
        • Tennessee Center for Clinical Trials
    • Texas
      • Amarillo, Texas, United States, 79106
        • Recruiting
        • PharmaTex Research
      • Brownsville, Texas, United States, 78520
        • Recruiting
        • PanAmerican Clinical Research
      • Dallas, Texas, United States, 75235
        • Recruiting
        • Southwest Family Medicine Associates
      • Houston, Texas, United States, 77061
        • Recruiting
        • Synergy Groups Medical
      • Houston, Texas, United States, 77002
        • Recruiting
        • East Texas Cardiology
      • Houston, Texas, United States, 77036
        • Recruiting
        • Synergy Group Medical,LLC
      • Lufkin, Texas, United States, 75901
        • Recruiting
        • Heart Institute of East Texas
      • McKinney, Texas, United States, 75071
        • Recruiting
        • Texas Institute of Cardiology PA
      • Missouri City, Texas, United States, 77459
        • Recruiting
        • Synergy Group Medical, LLC
    • Virginia
      • Vienna, Virginia, United States, 22182
        • Recruiting
        • Conquest Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  1. Has AF or flutter (paroxysmal or persistent), not considered to be secondary to a reversible cause

  2. At moderate to high risk for stroke defined as:

    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 ≥4 OR
    2. CHA2DS2-VA score of 3 AND at least 1 enrichment criteria as described in the protocol

  3. Shared decision making between the participant and provider determining that the bleeding risk of Oral Anticoagulant (OAC) therapy outweighs the benefits, making the participant unsuitable for OAC therapy as described in the protocol

Key Exclusion Criteria:

  1. Has a mechanical heart valve prosthesis (Note: transcatheter aortic valve replacement is not an exclusion)
  2. Had an ischemic stroke within 2 days prior to randomization
  3. Has persistent, uncontrolled hypertension (per investigator's discretion)
  4. Has a history of Central Nervous System (CNS) bleeding within 30 days prior to randomization
  5. Has a life expectancy less than 12 months
  6. Has participated in a prior Factor XI (FXI) inhibitor study

Note: Other protocol-defined Inclusion/ Exclusion criteria apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Drug: Placebo

Administered per the protocol
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Time to first occurrence of ischemic stroke or systemic embolism
Time Frame: Up to 36 months
Up to 36 months
Time to first occurrence of International Society on Thrombosis and Haemostasis (ISTH) major bleeding
Time Frame: Up to 36 months
Up to 36 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Severity of TEAEs
Time Frame: Up to 39 months
Up to 39 months
Time to first occurrence of Major Adverse Cardiovascular Event (MACE)
Time Frame: Up to 36 months
Up to 36 months
Time to first occurrence of MACE, pulmonary embolism, or Venous Thromboembolism (VTE)
Time Frame: Up to 36 months
Up to 36 months
Time to first occurrence of ischemic stroke
Time Frame: Up to 36 months
Up to 36 months
Time to Cardiovascular (CV) death
Time Frame: Up to 36 months
Up to 36 months
Time to all-cause death
Time Frame: Up to 36 months
Up to 36 months
Occurrence of Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Up to 39 months
Up to 39 months
Concentrations of REGN7508 over time
Time Frame: Up to 36 months
Up to 36 months
Concentrations of REGN9933 over time
Time Frame: Up to 36 months
Up to 36 months
Change from baseline in activated Partial Thromboplastin Time (aPTT) over time
Time Frame: Up to approximately 9 weeks
Up to approximately 9 weeks
Change from baseline in Prothrombin time (PT)/International Normalized Ratio (INR) over time
Time Frame: Up to approximately 9 weeks
Up to approximately 9 weeks
Occurrence of Anti-Drug Antibody (ADA) to REGN7508 over time
Time Frame: Up to 36 months
Up to 36 months
Magnitude of ADA to REGN7508 over time
Time Frame: Up to 36 months
Up to 36 months
Occurrence of ADA to REGN9933 over time
Time Frame: Up to 36 months
Up to 36 months
Magnitude of ADA to REGN9933 over time
Time Frame: Up to 36 months
Up to 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Regeneron Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 3, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 28, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 26, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 18, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 18, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 24, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 10, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • R9933-CVA-2495
  • 2025-521618-25-00 (Ctis)
  • 2025 (U.S. NIH Grant/Contract)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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