A Trial to Learn How Well REGN7508 Works for Preventing Blood Clots After a Knee Replacement in Adult Participants (ROXI-VTE II)

A Phase 2, Multicenter, Randomized, Open-Label, Active Control Study of REGN7508, a Factor XI Monoclonal Antibody, for Prevention of Venous Thromboembolism After Elective, Unilateral, Total Knee Arthroplasty (ROXI-VTE II)

This study is researching an experimental drug called REGN7508 (called "study drug"). The study is focused on adults undergoing elective, unilateral (one side) total knee replacement (TKR) surgery.

The aim of the study is to see how effective the study drug is at preventing venous thromboembolism (VTE) and other related diseases after unilateral total knee replacement surgery.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drug
• How much study drug is in the blood at different times
• Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: REGN7508; Drug: Enoxaparin

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
    • Multi-profile Hospital for Active Treatment Hearth and Brain EAD
  • Plovdiv, Bulgaria, 4002
    • Multiprofile Hospital For Active Treatment Park Hospital Ltd.
• Hungary
  • Budapest, Hungary, 1027
    • Budai Irgalmasrendi Korhaz
  • Szolnok, Hungary, 5000
    • Szolnoki MAV Hospital
• Latvia
  • Liepāja, Latvia, LV-3414
    • Liepaja Regional Hospital
  • Riga, Latvia, LV-1005
    • Hospital of Traumatology and Orthopaedics
  • Riga, Latvia, LV-1004
    • Riga's 2nd Hospital
  • Riga, Latvia, LV-1005
    • Orto Klinika
  • Valmieras Aprinkis
    • Valmiera, Valmieras Aprinkis, Latvia, LV-4201
      • Vidzemes Hospital
• Lithuania
  • Kaunas, Lithuania, LT-48142
    • Lithuanian University of Health Sciences Kaunas Hospital
  • Klaipėda, Lithuania, LT-92288
    • Klaipeda university hospital
  • Kaunas County
    • Kaunas, Kaunas County, Lithuania, LT-50161
      • Lietuvos sveikatos mokslu universiteto ligonine Kauno klinik
• Poland
  • Lesser Poland Voivodeship
    • Tarnów, Lesser Poland Voivodeship, Poland, 33-100
      • Specjalistyczny Szpital im. E. Szczeklika w Tarnowie
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 92-213
      • Clinic of Orthopaedics and Paediatric Orthopaedics

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Undergoing a primary elective unilateral TKA
2. Has a body weight ≤130 kg at screening visit
3. Is judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and electrocardiograms (ECG's) performed at screening and/or prior to administration of initial dose of study drug as described in the protocol
4. Is in good health based on laboratory safety testing obtained during the screening period as described in the protocol

Key Exclusion Criteria:

1. History of bleeding in the past 6 months prior to dosing requiring hospitalization or transfusion; history of intracranial or intraocular bleeding, excessive operative or post-operative bleeding, and traumatic spinal or epidural anesthesia; history of bleeding diathesis
2. History of thromboembolic disease or thrombophilia
3. History of major surgery, including brain, spinal, or ocular, within approximately the past 6 months
4. History of major trauma within approximately the past 6 months prior to dosing
5. Hospitalized (>24 hours) for any reason within 30 days of the screening visit
6. Has an estimated glomerular filtration rate (GFR) of <45 mL/min/1.73m^2 at the screening visit using one of the following formulas: the Modification of Diet in Renal Disease (MDRD) equation, the Chronic Kidney Disease Epidemiology Collaboration equation, or equivalent equation

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: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Enoxaparin	Drug: Enoxaparin; Administered by subcutaneous (SC) dose daily through the time of venography (or day 12, whichever is earlier); Other Names: Inhixa
Experimental: REGN7508	Drug: REGN7508; Administered by single intravenous (IV) dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Confirmed, Adjudicated Venous Thromboembolism (VTE)	Composite endpoint that includes asymptomatic deep DVT (deep venous thrombosis) detected by unilateral venography of the operated leg; confirmed symptomatic DVT of either leg; confirmed fatal or nonfatal pulmonary embolism (PE) including unexplained death for which PE cannot be ruled out.	Through day 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding	International Society on Thrombosis and Hemostasis (ISTH) criteria for Major Bleeding and CRNM Bleeding as described in the protocol	Through day 12
Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE)	A TEAE is any untoward medical occurrence in a participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.	Through day 75
Percentage of Participants With Major VTE	Major VTE is a composite endpoint that includes: proximal DVT; confirmed symptomatic DVT of either leg; confirmed fatal or nonfatal PE including unexplained death for which PE cannot be ruled out.	Through day 12
Percentage of Participants With Deep Venous Thrombosis (DVT)	DVT measured by venography of the operated leg	Through day 12
Concentrations of Total REGN7508 in Serum		Days 1, 5, 10, 30 and 75
Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT)	aPTT was used to measure the anticipated anticoagulant effect of REGN7508. Fold change is based on the follow-up value/baseline value within an arm.	Days 1, 5, 10, 30, 75
Fold Change From Baseline in Prothrombin Time (PT)	PT is a measure of extrinsic and/or common pathway function. Fold change is based on the follow-up value/baseline value within an arm.	Days 1, 5, 10, 30, 75
Number of Participants With Anti-REGN7508 Antibodies by Status	Immunogenicity characterized by anti-drug antibody (ADA) status	Through end of study; approximately Day 75
Number of Participants With Treatment-Emergent or Treatment-Boosted Anti-REGN7508 Antibodies by Maximum Titer	Immunogenicity characterized per by ADA status	Through end of study; approximately Day 75

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Weitz JI, Kithcart AP, O'Brien MP, Levy O, Marin E, Onisko M, Mohammadi KA, Li D, Meagher KA, Chang HH, Olenchock BA, Gutstein DE, Segers A, Roberts RS, Bonaca MP, Raskob GE. Efficacy and safety of REGN9933A2 and REGN7508Cat for preventing postoperative venous thromboembolism (ROXI-VTE-I and ROXI-VTE-II): two randomised, open-label, phase 2 trials. Lancet. 2025 Nov 29;406(10519):2551-2563. doi: 10.1016/S0140-6736(25)02097-5. Epub 2025 Nov 8.

Helpful Links

• A Plain Language Summary is available on TrialSummaries.com

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2024
• Primary Completion (Actual): November 19, 2024
• Study Completion (Actual): January 21, 2025

Study Registration Dates

• First Submitted: June 6, 2024
• First Submitted That Met QC Criteria: June 6, 2024
• First Posted (Actual): June 12, 2024

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Anti-factor XI (FXI) monoclonal antibody; Venous thromboembolism (VTE); Unilateral total knee arthroplasty (TKA)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Carbohydrates; Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Enoxaparin
• Other Study ID Numbers: R7508-DVT-2360; 2023-508602-14-00 (Other Identifier: EU CT Number)

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 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
• product manufactured in and exported from the U.S.: Yes