A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants

A Phase 2, Multicenter, Randomized, Open-Label, Active-Control Study of REGN9933, a Factor XI Monoclonal Antibody, for Prevention of Venous Thromboembolism After Elective, Unilateral, Total Knee Arthroplasty

The primary objective of the study is to evaluate the efficacy of REGN9933 for the prevention of venous thromboembolism (VTE) after unilateral total knee arthroplasty (TKA), compared to enoxaparin

The secondary objectives of the study are:

• To evaluate the bleeding risk (ie, major and clinically relevant non-major [CRNM] bleeding) of REGN9933 after unilateral TKA through time of venography, compared to enoxaparin
• To assess overall safety and tolerability of REGN9933 in participants undergoing TKA
• To evaluate the efficacy of REGN9933 in prevention of clinically relevant VTE, compared to enoxaparin
• To evaluate the efficacy of REGN9933 in prevention of deep venous thrombosis (DVT) detected by venography, compared to enoxaparin
• To evaluate the pharmacokinetics (PK) of REGN9933 after single intravenous (IV) administration
• To assess pharmacodynamic (PD) effects of REGN9933 on intrinsic and extrinsic coagulation pathways
• To assess immunogenicity following a single dose of REGN9933 over time
• To compare the efficacy of enoxaparin and apixaban in prevention of VTE after unilateral TKA

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: REGN9933; Drug: Enoxaparin; Drug: Apixiban

• Study Type: Interventional
• Enrollment (Actual): 373
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Limburg
    • Genk, Limburg, Belgium, 3600
      • Ziekenhuis Oost-Limburg- Campus Sint-Jan
• Bulgaria
  • Pleven, Bulgaria, 5800
    • MBAL Heart and Brain Hospital
• Canada
  • Ontario
    • Ajax, Ontario, Canada, L1S 7K7
      • Durham Bone and Joint Specialists
• Hungary
  • Kaposvár, Hungary, 7400
    • Department of Orthopedics, Somogy County Mór Kaposi Teaching Hospital
  • Jász-Nagykun-Szolnok
    • Szolnok, Jász-Nagykun-Szolnok, Hungary, 5000
      • MAV Korhaz es Rendelointezet Szolnok
• Latvia
  • Liepāja, Latvia, LV3414
    • Liepaja Regional Hospital
  • Riga, Latvia, LV-1004
    • Riga's 2nd Hospital
  • Riga, Latvia, LV-1002
    • Vidzemes Hospital
  • Riga, Latvia, LV1005
    • Hospital of Traumatology and Orthopaedics
• Lithuania
  • Kaunas, Lithuania, LT-44320
    • Lietuvos sveikatos mokslu universiteto Kauno ligonine
  • Kaunas County
    • Kaunas, Kaunas County, Lithuania, LT-50009
      • Lietuvos sveikatos mokslų universiteto ligoninė Kauno klinik
  • Klaipėda County
    • Klaipėda, Klaipėda County, Lithuania, LT-92288
      • Klaipeda University Hospital
• Poland
  • Lodz, Poland, 90-153
    • SP ZOZ Centralny Szpital Kliniczny UM w Lodzi
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
  • Radzyń Podlaski, Poland, 21-300
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Radzyniu Podlaskim
  • Lesser Poland Voivodeship
    • Tarnów, Lesser Poland Voivodeship, Poland, 33-100
      • Specjalistyczny Szpital im. E. Szczeklika w Tarnowie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Undergoing 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) performed at screening and/or prior to administration of initial dose of study drug
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 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.
5. Hospitalized (>24 hours) for any reason within 30 days of the screening visit
6. Using the Modification of Diet in Renal Disease equation, has an estimated glomerular filtration rate as described in the protocol

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGN9933; REGN9933 will be administered by intravenous (IV) infusion	Drug: REGN9933; Participants will receive a single dose of REGN9933 by IV infusion
Active Comparator: Enoxaparin; Enoxaparin will be administered by subcutaneous (SC) administration	Drug: Enoxaparin; Participants will receive enoxaparin by SC administration daily through the time of venography (or day 12, whichever is earlier); Other Names: Lovenox
Active Comparator: Apixaban; Apixaban will be administered orally twice a day	Drug: Apixiban; Participants will receive apixaban orally twice a day through the time of venography (or day 12, whichever is earlier); Other Names: Eliquis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Confirmed, Adjudicated Venous Thromboembolism (VTE) (REGN9933 vs Enoxaparin)	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.	Up to Day 75
Percentage of Participants With Major VTE (REGN9933 vs Enoxaparin)	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 DVT (REGN9933 vs Enoxaparin)	DVT measured by venography of the operated leg	Through Day 12
Total REGN9933 Concentrations in Serum	The concentrations of REGN9933 over time were summarized by descriptive statistics by study arm for the overall population	Days 0.0625 (post-dose), 4, 9, 29, and 74
Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT)	aPTT was used to measure the anticipated anticoagulant effect of REGN9933. Fold change is based on the follow-up value/baseline value within an arm.	Days 1, 5, 10, 30, and 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, and 75
Number of Participants With Anti-REGN9933 Antibodies by Status	Immunogenicity characterized by anti-drug antibody (ADA) status	Through Day 75
Number of Participants With Treatment-Emergent or Treatment-Boosted Anti-REGN13335 Antibodies by Maximum Titer Level	Immunogenicity characterized per drug molecule by ADA status	Through Day 75
Percentage of Participants With Confirmed, Adjudicated VTE (Enoxaparin vs Apixaban)	Asymptomatic deep DVT 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

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Related Info
• A Plain Language Summary is available on TrialSummaries.com

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2023
• Primary Completion (Actual): May 27, 2024
• Study Completion (Actual): May 27, 2024

Study Registration Dates

• First Submitted: November 8, 2022
• First Submitted That Met QC Criteria: November 8, 2022
• First Posted (Actual): November 16, 2022

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Deep Vein Thrombosis; Anti-factor XI (FXI) monoclonal antibody; Unilateral total knee arthroplasty (TKA),
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis; Thromboembolism; Thrombosis; Venous Thrombosis; Venous Thromboembolism; Carbohydrates; Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Enoxaparin; apixaban
• Other Study ID Numbers: R9933-DVT-2230; 2022-501470-18-00 (Other Identifier: EU CT)

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, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has 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