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)

Atrial fibrillation (often shortened to AF) is a heart condition that causes an irregular and often unusually fast heartbeat. When the heart does not beat in a steady rhythm, blood can pool inside its chambers. This makes it easier for blood clots to form. If a clot travels through the bloodstream to the brain, it can block blood flow and cause a stroke.

Standard care usually involves taking blood-thinning tablets (anticoagulants). While these medicines work well to prevent clots, they also slow down the body's natural ability to stop bleeding. For some people, such as those with a history of severe bleeding or certain other health conditions, standard blood thinners are considered too risky to use. This leaves them without an effective way to lower their stroke risk.

The ROXI-INCLINE trial is studying two new treatments, REGN7508 and REGN9933. These are laboratory-made antibodies designed to block Factor XI, a protein that plays a key role in forming dangerous clots. Scientists hope that targeting Factor XI will prevent strokes while still allowing the body to stop ordinary bleeding from cuts and minor injuries.

In this study, researchers will compare both medicines against an inactive dummy treatment (a placebo). This helps them prove whether the new treatments are truly safe and effective for people who cannot take standard blood thinners.