Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease (ROXI-PALISADE)

Regeneron Pharmaceuticals

Status and phase: Begins enrollment in 1 month; Phase 3

Conditions: Peripheral Artery Disease (PAD)

Treatments: Drug: REGN9933; Drug: Rivaroxaban; Drug: Placebo; Drug: REGN7508

Study type: Interventional

Funder types: Industry

Identifiers

NCT07318610

R9933-PAD-2394

2025-522954-37-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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

Enrollment: 7,050 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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7,050 participants in 2 patient groups

Cohort 1

Experimental group

Treatment:

Drug: Placebo

Drug: REGN7508

Drug: REGN9933

Cohort 2

Experimental group

Treatment:

Drug: Rivaroxaban

Drug: REGN7508

Drug: REGN9933