Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease

Official title

A Master Protocol for a Phase 3, Multicenter, Randomized Study to Evaluate the Efficacy and Safety of REGN7508 and REGN9933, Monoclonal Antibodies Against Factor XI, in Participants With Recent Lower Extremity Revascularization for Symptomatic Peripheral Artery Disease (ROXI-PALISADE)

Overview

This study is researching 2 different experimental drugs called REGN7508 and REGN9933. The study is focused on people who have Peripheral Artery Disease (PAD), which means that the blood vessels in their arms and legs have become too narrow. People with PAD have a higher risk of getting blood clots after procedures like Lower Extremity Revascularization (LER), a procedure to improve blood flow in the legs and feet. The aim of this study is to see how well REGN7508 and REGN9933 prevent life-threatening blood clots in participants with PAD who have recently had LER. The effects of REGN7508 and REGN9933, individually, will also be compared to rivaroxaban and a placebo. The study is looking at several other research questions, including: * What side effects might happen from taking the study drugs and how do they compare to the side effects of rivaroxaban * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects) * If the study drugs affect the ability of the blood to clot normally

Interventions

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

Primary outcome measures

• Time-to-first occurrence of a major thrombotic vascular event, consisting of Acute Limb Ischemia (ALI), major amputation (above the ankle) of vascular etiology, Myocardial Infarction (MI), ischemic stroke, or Cardiovascular (CV) death [Time frame: Approximately up to 42 months]
• Time-to-first occurrence of International Society of Thrombosis and Hemostasis (ISTH) major or Clinically Relevant Non-major (CRNM) bleeding [Time frame: Approximately up to 42 months]

Secondary outcome measures (12)

• Total (first and subsequent) occurrences of major thrombotic vascular events, consisting of ALI, major amputation (above the ankle) of vascular etiology, MI, ischemic stroke, or CV death [Time frame: Approximately up to 42 months]
• Time-to-first occurrence of an expanded thrombotic vascular event, consisting of ALI, major amputation (above the ankle) of vascular etiology, MI, ischemic stroke, CV death, unplanned index limb revascularization, or Venous Thromboembolism (VTE) [Time frame: Approximately up to 42 months]
• Time-to-first occurrence of ALI, major amputation (above the ankle) of vascular etiology, MI, ischemic stroke or coronary death [Time frame: Approximately up to 42 months]
• Time-to-first occurrence of vascular hospitalization for a coronary cerebrovascular, or peripheral event of thrombotic nature [Time frame: Approximately up to 42 months]
• Time-to-first occurrence of ALI, major amputation of vascular etiology, MI, ischemic stroke, or all-cause mortality [Time frame: Approximately up to 42 months]
• Time-to-first occurrence of unplanned index limb revascularization for ischemia [Time frame: Approximately up to 42 months]
• Time-to-first occurrence of VTE [Time frame: Approximately up to 42 months]
• Time-to-all-cause mortality [Time frame: Approximately up to 42 months]
• Time-to-first occurrence of Major Adverse Limb Event (MALE) [Time frame: Approximately up to 42 months]
• Time-to-first occurrence of Major Adverse Cardiovascular Event (MACE) [Time frame: Approximately up to 42 months]
• Time-to-first occurrence of a major thrombotic vascular event or ISTH fatal/critical organ bleeding (net clinical benefit) [Time frame: Approximately up to 42 months]
• Time-to-first occurrence of Thrombolysis in Myocardial Infarction (TIMI) major bleeding [Time frame: Approximately up to 42 months]

Eligibility criteria

Inclusion criteria

• Successful LER distal to the external iliac artery for ischemia due to atherosclerotic disease within 10 days prior to randomization as described in the protocol
• At least 1 of the following enrichment factors for major thrombotic vascular events:

• Bypass with prosthetic graft
• Endovascular treatment with stenting
• Target lesion length >15 cm
• History of LER or amputation for PAD prior to qualifying LER
• Type 2 diabetes mellitus requiring pharmacologic treatment
• Comorbid symptomatic coronary artery disease as described in the protocol
• Chronic kidney disease as described in the protocol
• Age ≥75 years

Exclusion criteria

• Has any active clinical condition requiring chronic therapeutic anticoagulation after the index revascularization including known triple positive antiphospholipid syndrome
• Has known bleeding diathesis, platelet count <50,000/mm\^3 or history of non-traumatic intracerebral hemorrhage, known cerebral amyloid angiopathy, or known unrepaired cerebrovascular malformations
• Has recent coronary revascularization as described in the protocol
• For Cohort 2 only: Has estimated Glomerular Filtration Rate (eGFR) <15 mL/min/1.73m\^2 within 14 days prior to randomization or on dialysis or expected to be started on dialysis within the next 12 weeks starting from randomization
• Has any other condition or therapy which would make the participant unsuitable for this study or not allow participation for the full planned study period
• Has allergy, hypersensitivity, or other contraindication to REGN7508, REGN9933, or rivaroxaban (Cohort 2 only) or their excipients

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

Treatment

Study locations

United States · 13 centers

• Lake Martin Medical and Vascular Center — Alexander City
• Axsendo Clinical Research, Integrated Medical Services — Avondale
• Applied Research Center of Arkansas — Little Rock
• Nature Coast Clinical Research - Cardiology — Crystal River
• Profound Research, Powers Health Medical Group — Munster
• Cardiovascular Solutions — Shreveport
• Accellacare of Piedmont, Piedmont Healthcare — Mooresville
• Apex Research Foundation, LLC — Jackson
• … and 5 more centers

Identifiers

NCT: NCT07318610 · R9933-PAD-2394 · 2025-522954-37-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗