Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation

Official title

A Phase 2, Randomized, Multicenter, Open-label, Blinded-endpoint Study to Evaluate the Safety of REGN7508 and REGN9933, Monoclonal Antibodies Against FXI, Versus Apixaban in Participants With Atrial Fibrillation (ROXI-ATLAS)

Overview

This study is researching experimental drugs called REGN7508 and REGN9933. The study is focused on participants who have atrial fibrillation, which means that the heart beats too fast and unevenly. 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 well REGN7508 and REGN9933 work in patients that get medicine for their atrial fibrillation. The bleeding effects of REGN7508 and REGN9933 will be compared to another medicine (apixaban), which is available on the market to treat and prevent formation of blood clots. The study is looking at several other research questions, including: * What side effects may happen from taking REGN7508 or REGN9933 * How well do the study drugs reduce the risk of having a stroke * How much of REGN7508 or REGN9933 is in the blood at different times * Whether the body makes antibodies against REGN7508 or REGN9933 (which could make the drugs less effective or could lead to side effects)

Interventions

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

Primary outcome measures

• Incidence of any bleeding [Time frame: 12 weeks]

Secondary outcome measures (12)

• Incidence of the composite of ISTH major bleeding or ISTH CRNM bleeding [Time frame: 12 weeks]
• Incidence of ISTH major bleeding [Time frame: 12 weeks]
• Incidence of ISTH CRNM bleeding [Time frame: 12 weeks]
• Incidence of minor bleeding [Time frame: 12 weeks]
• Number of ISTH major bleeding events [Time frame: 12 weeks]
• Number of ISTH CRNM bleeding events [Time frame: 12 weeks]
• Number of minor bleeding events [Time frame: 12 weeks]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Approximately 25 weeks]
• Severity of TEAEs [Time frame: Approximately 25 weeks]
• Incidence of the composite of stroke or systemic embolism [Time frame: Approximately 12 weeks]
• Incidence of Antidrug Antibodies (ADA) to REGN7508 [Time frame: 12 weeks]
• Magnitude of ADA to REGN7508 [Time frame: 12 weeks]

Eligibility criteria

Inclusion criteria

• Has AF or flutter (paroxysmal or persistent), not felt to be secondary to a reversible cause, and an indication for indefinite anticoagulation treatment as described in the protocol
• Meets one of the following:

• CHA2DS2-VA \[C: Congestive heart failure; H: Hypertension; A2: Age ≥75 years (double points); D: Diabetes mellitus; S2: Stroke or TIA or Thromboembolism (double points); V: Vascular disease; A: Age 65-74 years\] score ≥2 and Oral Anticoagulant (OAC) naïve or
• CHA2DS2-VA score ≥3 or
• CHA2DS2-VA score of 2 and at least 1 enrichment criteria as described in the protocol
• Must have an International Normalization Ratio (INR) <2.5 at the time of randomization if taking warfarin or another Vitamin K Antagonist (VKA)

Exclusion criteria

• Has a mechanical heart valve prosthesis (Note: transcatheter aortic valve replacement is not an exclusion)
• Has known moderate-to-severe mitral stenosis
• Has had successful ablation therapy or Left Atrial Appendage (LAA) occlusion/exclusion, or planned ablation or LAA occlusion/exclusion as described in the protocol
• Had an ischemic stroke within 2 days prior to randomization
• Has estimated Glomerular Filtration Rate (eGFR) <15 mL/min/1.73m\^2 within 30 days prior to randomization or on dialysis or expected to be started as described in the protocol
• Has a history of central nervous system bleeding within 30 days prior to randomization

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

Single blind

Primary purpose

Prevention

Study locations

United States · 42 centers

• SEC Clinical Research — Dothan
• Eastern Shore Research Institute — Fairhope
• Valley Clinical Trials, Inc — Covina
• North Coast Cardiology — Encinitas
• Mission Cardiovascular Research Institute — Fremont
• National Institute of California Heart and Vein Specialists — Huntington Beach
• Profound Research LLC at Southern California Heart Specialists — Pasadena
• Empire Clinical Research — Pomona
• … and 34 more centers

Brazil · 15 centers

• Hospital Ruy Azeredo — Goiânia
• Cardiologia Assistencial e de Pesquisa Ltda (Cardresearch) — Belo Horizonte
• Nucleo de Pesquisa do Hospital Cardiologico Costantini (NUPEC) — Belo Horizonte
• Hospital Maternidade e Pronto Socorro Santa Lucia — Poços de Caldas
• Sociedade Hospitalar Angelina Caron — Campina Grande do Sul
• Pontificia Universidade Catolica do Paraná (PUC) Trials — Curitiba
• Nucleo de Pesquisa Clínica SS — Curitiba
• Hospital Ernesto Dornelles — Porto Alegre
• … and 7 more centers

Canada · 13 centers

• University of Alberta Hospital - Cardiology — Edmonton
• Victoria Cardiac Arrhythmia Trials — Victoria
• GA Research Associates Ltd. — Moncton
• Health sciences North - Cardiology — Greater Sudbury
• Hamilton Health Sciences Corporation — Hamilton
• Hamilton Medical Research Group (HMRG) — Hamilton
• Dr James Cha — Oshawa
• Heart Health Institute Research Inc. - Cardiology — Scarborough Village
• … and 5 more centers

Argentina · 4 centers

• Centro de Investigacion Clinica — Ciudad Autonoma de Buenos Aires
• Fundacion Estudios Clinicos - Cardiologia — Rosario
• STAT Research Argentina — Buenos Aires
• Centro de Investigaciones Clinicas del Litoral - Cardiologia — Santa Fe

Identifiers

NCT: NCT07175428 · R7508-CVA-2393

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗