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

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)

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 Overview

• Status: Recruiting
• Conditions: Peripheral Artery Disease (PAD)
• Intervention / Treatment: Drug: Placebo; Drug: REGN7508; Drug: REGN9933; Drug: Rivaroxaban

• Study Type: Interventional
• Enrollment (Estimated): 7050
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• United States
  • Texas
    • Amarillo, Texas, United States, 79106
      • Recruiting
      • PharmaTex Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 of the following enrichment factors 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 pharmacologic 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 chronic 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 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
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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1	Drug: Placebo; Administered per the protocol; Drug: REGN7508; Administered per the protocol; Other Names: cenvacibart; Drug: REGN9933; Administered per the protocol; Other Names: amrecibart
Experimental: Cohort 2	Drug: REGN7508; Administered per the protocol; Other Names: cenvacibart; Drug: REGN9933; Administered per the protocol; Other Names: amrecibart; Drug: Rivaroxaban; Administered per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Approximately up to 42 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	Approximately up to 42 months
Time-to-first occurrence of unplanned index limb revascularization for ischemia	Cohort 1	Approximately up to 42 months
Time-to-first occurrence of VTE	Cohort 1	Approximately up to 42 months
Time-to-all-cause mortality	Cohort 1	Approximately up to 42 months
Time-to-first occurrence of Major Adverse Limb Event (MALE)	Cohort 1	Approximately up to 42 months
Time-to-first occurrence of Major Adverse Cardiovascular Event (MACE)	Cohort 1	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	Approximately up to 42 months
Time-to-first occurrence of Thrombolysis in Myocardial Infarction (TIMI) major bleeding	Cohort 1 and 2	Approximately up to 42 months
Occurrence of Treatment-Emergent Adverse Event (TEAEs)	Cohort 1 and 2	Approximately up to 45 months
Severity of TEAEs	Cohort 1 and 2	Approximately up to 45 months
Occurrence of Anti-Drug Antibody (ADA) to REGN7508 over time	Cohort 1 and 2	Approximately up to 45 months
Magnitude of ADA to REGN7508 over time	Cohort 1 and 2	Approximately up to 45 months
Occurrence of ADA to REGN9933 over time	Cohort 1 and 2	Approximately up to 45 months
Magnitude of ADA to REGN9933 over time	Cohort 1 and 2	Approximately up to 45 months
Concentrations of REGN7508 over time	Cohort 1 and 2	Approximately up to 45 months
Concentrations of REGN9933 over time	Cohort 1 and 2	Approximately up to 45 months
Change from baseline in activated Partial Thromboplastin Time (aPTT) over time	Cohort 1 and 2	Approximately up to week 9
Change from baseline in Prothrombin Time (PT)/International Normalization Ratio (INR) over time	Cohort 1 and 2	Approximately up to week 9
Total (first and subsequent) occurrences of expanded thrombotic vascular events	Cohort 2	Approximately up to 42 months
Time-to-first occurrence of a major thrombotic vascular event	Cohort 2	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	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	Approximately up to 42 months
Time-to-first occurrence of vascular hospitalization for a coronary cerebrovascular, or peripheral event of thrombotic nature	Cohort 1	Approximately up to 42 months

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): May 29, 2026
• Primary Completion (Estimated): August 18, 2029
• Study Completion (Estimated): November 16, 2029

Study Registration Dates

• First Submitted: January 2, 2026
• First Submitted That Met QC Criteria: January 2, 2026
• First Posted (Actual): January 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Blood clots; Lower Extremity Revascularization (LER)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Thrombosis; Peripheral Arterial Disease; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines; Thiophenes; Rivaroxaban
• Other Study ID Numbers: R9933-PAD-2394; 2025-522954-37-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No