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

Phase 3Not Yet RecruitingNCT07318610

Regeneron Pharmaceuticals7,050 enrolled

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

7,050

Conditions

Peripheral Artery Disease (PAD)

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. 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 2. At least 1 enrichment factor for major thrombotic vascular events: 1. Bypass with prosthetic graft 2. Endovascular treatment with stenting 3. Target lesion length \>15 cm 4. History of LER or amputation for PAD prior to qualifying LER 5. Type 2 diabetes mellitus requiring treatment 6. Comorbid symptomatic coronary artery disease as described in the protocol 7. Chronic kidney disease as described in the protocol 8. Age ≥75 years Key Exclusion Criteria: 1. Has any active clinical condition requiring therapeutic anticoagulation after the index revascularization including known triple positive antiphospholipid syndrome 2. 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 3. Has recent coronary revascularization as described in the protocol 4. For Cohort 2 only: Has Glomerular Filtration Rate (GFR) \<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 5. 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 6. 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

Outcomes

Primary Outcomes

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

Cohort 1

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

Cohort 1 and 2

Time frame: Approximately up to 42 months

Secondary Outcomes

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

Cohort 1 and 2

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)

Cohort 1 and 2

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

Cohort 1

Time frame: Approximately up to 42 months

Time-to-first occurrence of vascular hospitalization for a coronary or peripheral event of thrombotic nature

Cohort 1

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

Cohort 1

Time frame: Approximately up to 42 months

Time-to-first occurrence of unplanned index limb revascularization for ischemia

Cohort 1

Time frame: Approximately up to 42 months

Time-to-first occurrence of VTE

Cohort 1

Time frame: Approximately up to 42 months

Time-to-all-cause mortality

Cohort 1

Time frame: Approximately up to 42 months

Time-to-first occurrence of Major Adverse Limb Event (MALE)

Cohort 1

Time frame: Approximately up to 42 months

Time-to-first occurrence of Major Adverse Cardiovascular Event (MACE)

Cohort 1

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)

Cohort 1

Time frame: Approximately up to 42 months

Time-to-first occurrence of Thrombolysis in Myocardial Infarction (TIMI) major bleeding

Cohort 1 and 2

Time frame: Approximately up to 42 months

Occurrence of Treatment-Emergent Adverse Event (TEAEs)

Cohort 1 and 2

Time frame: Approximately up to 45 months

Severity of TEAEs

Cohort 1 and 2

Time frame: Approximately up to 45 months

Occurrence of Anti-Drug Antibody (ADA) to REGN7508 over time

Cohort 1 and 2

Time frame: Approximately up to 45 months

Magnitude of ADA to REGN7508 over time

Cohort 1 and 2

Time frame: Approximately up to 45 months

Occurrence of ADA to REGN9933 over time

Cohort 1 and 2

Time frame: Approximately up to 45 months

Magnitude of ADA to REGN9933 over time

Cohort 1 and 2

Time frame: Approximately up to 45 months

Concentrations of REGN7508 over time

Cohort 1 and 2

Time frame: Approximately up to 45 months

Concentrations of REGN9933 over time

Cohort 1 and 2

Time frame: Approximately up to 45 months

Change from baseline in activated Partial Thromboplastin Time (aPTT) over time

Cohort 1 and 2

Time frame: Approximately up to week 9

Change from baseline in Prothrombin Time (PT)/International Normalization Ratio (INR) over time

Cohort 1 and 2

Time frame: Approximately up to week 9

Total (first and subsequent) occurrences of expanded thrombotic vascular events

Cohort 2

Time frame: Approximately up to 42 months

Time-to-first occurrence of a major thrombotic vascular event

Cohort 2

Time frame: Approximately up to 42 months

Total (first and subsequent) occurrences of ALI, major amputation (above the ankle) of vascular etiology, MI, all-cause stroke, or CV death

Cohort 2

Time frame: Approximately up to 42 months

Total (first and subsequent) occurrences of ALI, major amputation (above the ankle) of vascular etiology, MI, all-cause stroke, CV death, unplanned index limb revascularization, or VTE

Cohort 2

Time frame: Approximately up to 42 months

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts