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

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)

Overview

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)

Interventions

• Drug REGN7508
  Administered per the protocol
• Drug REGN9933
  Administered per the protocol
• Drug Placebo
  Administered per the protocol

Primary outcome measures

• Time to first occurrence of ischemic stroke or systemic embolism [Time frame: Up to 36 months]
• Time to first occurrence of International Society on Thrombosis and Haemostasis (ISTH) major bleeding [Time frame: Up to 36 months]

Secondary outcome measures (12)

• Time to first occurrence of Major Adverse Cardiovascular Event (MACE) [Time frame: Up to 36 months]
• Time to first occurrence of MACE, pulmonary embolism, or Venous Thromboembolism (VTE) [Time frame: Up to 36 months]
• Time to first occurrence of ischemic stroke [Time frame: Up to 36 months]
• Time to Cardiovascular (CV) death [Time frame: Up to 36 months]
• Time to all-cause death [Time frame: Up to 36 months]
• Occurrence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Up to 39 months]
• Severity of TEAEs [Time frame: Up to 39 months]
• Concentrations of REGN7508 over time [Time frame: Up to 36 months]
• Concentrations of REGN9933 over time [Time frame: Up to 36 months]
• Change from baseline in activated Partial Thromboplastin Time (aPTT) over time [Time frame: 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]
• Occurrence of Anti-Drug Antibody (ADA) to REGN7508 over time [Time frame: Up to 36 months]

Eligibility criteria

Inclusion criteria

• Has AF or flutter (paroxysmal or persistent), not considered to be secondary to a reversible cause
• At moderate to high risk for stroke defined as:

• 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
• CHA2DS2-VA score of 3 AND at least 1 enrichment criteria as described in the protocol
• 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

Exclusion criteria

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

Note: Other protocol-defined Inclusion/ Exclusion criteria apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

United States · 18 centers

• SEC Clinical Research — Dothan
• Mission Cardiovascular Research Institute — Fremont
• National Institute of California Heart and Vein Specialists — Huntington Beach
• Profound Research LLC at Southern California Heart Specialists — Pasadena
• Cardiology Associates Medical Group — Ventura
• Interventional Cardiology Medical Group — West Hills
• South Florida Research Organization LLC — Medley
• Sec Clinical Research — Pensacola
• … and 10 more centers

Identifiers

NCT: NCT07430956 · R9933-CVA-2495 · 2025-521618-25-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗