Stroke and Systemic Embolism Prevention in Adult Participants With Atrial Fibrillation for Whom Oral Anticoagulation is Unsuitable

NCT07430956
clinicaltrials.gov
Phase
Phase 3
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Recruitment status
Recruiting
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Participants
2,628
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Lead sponsor
Regeneron Pharmaceuticals
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Start date
2026-04-03
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Number of sites
18
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Summary
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)
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Acronym
ROXI-INCLINE
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Short title
Stroke and Systemic Embolism Prevention in Adult Participants With Atrial Fibrillation for Whom Oral Anticoagulation is Unsuitable
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Official title
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)
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Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2029-06-26
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First posted
2026-02-24
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Registry last updated
2026-06-23
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Primary completion date
2029-03-28
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Start date
2026-04-03
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Participants
2,628
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Participant count basis
Estimated
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Planned participants
2,628
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Protocol amendments
1
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Number of sites
18
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Regeneron Pharmaceuticals
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Source registry
ClinicalTrials.gov
clinicaltrials.gov

Registry ID
NCT07430956
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ClinicalTrials.gov ID
NCT07430956
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Prevention
Masking
Quadruple masking
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Time to first occurrence of ischemic stroke or systemic embolism

    Timeframe: Up to 36 months

  2. Time to first occurrence of International Society on Thrombosis and Haemostasis (ISTH) major bleeding

    Timeframe: Up to 36 months

  1. Time to first occurrence of Major Adverse Cardiovascular Event (MACE)

    Timeframe: Up to 36 months

  2. Time to first occurrence of MACE, pulmonary embolism, or Venous Thromboembolism (VTE)

    Timeframe: Up to 36 months

  3. Time to first occurrence of ischemic stroke

    Timeframe: Up to 36 months

  4. Time to Cardiovascular (CV) death

    Timeframe: Up to 36 months

  5. Time to all-cause death

    Timeframe: Up to 36 months

  6. Occurrence of Treatment-Emergent Adverse Events (TEAEs)

    Timeframe: Up to 39 months

  7. Severity of TEAEs

    Timeframe: Up to 39 months

  8. Concentrations of REGN7508 over time

    Timeframe: Up to 36 months

  9. Concentrations of REGN9933 over time

    Timeframe: Up to 36 months

  10. Change from baseline in activated Partial Thromboplastin Time (aPTT) over time

    Timeframe: Up to approximately 9 weeks

  11. Change from baseline in Prothrombin time (PT)/International Normalized Ratio (INR) over time

    Timeframe: Up to approximately 9 weeks

  12. Occurrence of Anti-Drug Antibody (ADA) to REGN7508 over time

    Timeframe: Up to 36 months

  13. Magnitude of ADA to REGN7508 over time

    Timeframe: Up to 36 months

  14. Occurrence of ADA to REGN9933 over time

    Timeframe: Up to 36 months

  15. Magnitude of ADA to REGN9933 over time

    Timeframe: Up to 36 months

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

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

Sources for eligibility
clinicaltrials.gov

  • SEC Clinical ResearchDothan, United StatesRecruiting
  • Mission Cardiovascular Research InstituteFremont, United StatesRecruiting
  • National Institute of California Heart and Vein SpecialistsHuntington Beach, United StatesRecruiting
  • Profound Research LLC at Southern California Heart SpecialistsPasadena, United StatesRecruiting
  • Cardiology Associates Medical GroupVentura, United StatesRecruiting
  • Interventional Cardiology Medical GroupWest Hills, United StatesRecruiting
  • South Florida Research Organization LLCMedley, United StatesRecruiting
  • Sec Clinical ResearchPensacola, United StatesRecruiting
  • Clinical Site Partners, LLC DBA Flourish ResearchWinter Park, United StatesRecruiting
  • NSC Research, IncJohns Creek, United StatesRecruiting
  • Monroe Research, LLCWest Monroe, United StatesRecruiting
  • Profound Research, Millennium CardiologyFarmington Hills, United StatesRecruiting
  • AA Medical Research Center (MRC)Flint, United StatesRecruiting
  • K&R Research LLCMarion, United StatesRecruiting
  • AnMed HealthAnderson, United StatesRecruiting
  • PharmaTex ResearchAmarillo, United StatesRecruiting
  • Southwest Family Medicine AssociatesDallas, United StatesRecruiting
  • Texas Institute of Cardiology PAMcKinney, United StatesRecruiting
Sources for sites
clinicaltrials.gov

  • 2025
  • 2025-521618-25-00
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (5)

Targets (2)