Preventing stroke and systemic embolism in adults with atrial fibrillation who can't use oral blood thinners

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)

Phase 3 Interventional Regeneron Pharmaceuticals · NCT07430956

This trial tests two experimental drugs, REGN7508 and REGN9933, to see if they reduce ischemic stroke or systemic embolism in adults with atrial fibrillation who cannot or choose not to take oral blood thinners.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment2628 (estimated)
Ages18 Years and up
SexAll
SponsorRegeneron Pharmaceuticals Industry-sponsored
Locations5 sites (Dothan, Alabama and 4 other locations)
Trial IDNCT07430956 on ClinicalTrials.gov

What this trial studies

This Phase 3, randomized, placebo-controlled trial compares REGN7508 and REGN9933, given separately, against placebo in adults with atrial fibrillation judged unsuitable for oral anticoagulation. Eligible participants meet defined CHA2DS2-VA stroke-risk criteria and have a shared decision with their clinician that oral anticoagulants are inappropriate. The study tracks ischemic stroke, systemic embolism, and safety outcomes to compare event rates and side effects between each investigational drug and placebo. Enrollment occurs at several U.S. clinical research centers.

Who should consider this trial

Good fit: Adults with atrial fibrillation at moderate-to-high stroke risk who, after shared decision-making with their clinician, are judged unsuitable for oral anticoagulant therapy per the protocol are the intended participants.

Not a fit: People who can take standard oral anticoagulants, as well as those with mechanical heart valves, very recent ischemic stroke, or uncontrolled hypertension, are unlikely to benefit or may be excluded.

Why it matters

Potential benefit: If successful, these drugs could provide an alternative way to lower stroke and embolism risk for people with AF who cannot take standard oral blood thinners.

How similar studies have performed: Other anticoagulant approaches targeting similar clotting pathways have shown promise in early-phase trials, but large phase-3 evidence for non-oral alternatives is still limited.

Eligibility criteria

Show full inclusion / exclusion criteria
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

Where this trial is running

Dothan, Alabama and 4 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Atrial FibrillationBlood clotsIschemic strokeSystemic embolismPulmonary embolismVenous Thromboembolism
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.