NCT05618808

Brief Summary

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

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
373

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started May 2023

Shorter than P25 for phase_2

Geographic Reach
7 countries

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 8, 2022

Completed
8 days until next milestone

First Posted

Study publicly available on registry

November 16, 2022

Completed
6 months until next milestone

Study Start

First participant enrolled

May 24, 2023

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 27, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 27, 2024

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

July 16, 2025

Completed
Last Updated

August 29, 2025

Status Verified

August 1, 2025

Enrollment Period

1 year

First QC Date

November 8, 2022

Results QC Date

May 16, 2025

Last Update Submit

August 27, 2025

Conditions

Venous Thromboembolism

Keywords

Anti-factor XI (FXI) monoclonal antibodyDeep Vein ThrombosisUnilateral total knee arthroplasty (TKA),

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (10)

  • Number of Participants With Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding

    Through Day 12

  • Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE)

    Up to Day 75

  • Percentage of Participants With Major VTE (REGN9933 vs Enoxaparin)

    Through Day 12

  • Percentage of Participants With DVT (REGN9933 vs Enoxaparin)

    Through Day 12

  • Total REGN9933 Concentrations in Serum

    Days 0.0625 (post-dose), 4, 9, 29, and 74

  • +5 more secondary outcomes

Study Arms (3)

REGN9933

EXPERIMENTAL

REGN9933 will be administered by intravenous (IV) infusion

Drug: REGN9933

Enoxaparin

ACTIVE COMPARATOR

Enoxaparin will be administered by subcutaneous (SC) administration

Drug: Enoxaparin

Apixaban

ACTIVE COMPARATOR

Apixaban will be administered orally twice a day

Drug: Apixiban

Interventions

REGN9933DRUG

Participants will receive a single dose of REGN9933 by IV infusion

REGN9933
EnoxaparinDRUG

Participants will receive enoxaparin by SC administration daily through the time of venography (or day 12, whichever is earlier)

Also known as: Lovenox
Enoxaparin
ApixibanDRUG

Participants will receive apixaban orally twice a day through the time of venography (or day 12, whichever is earlier)

Also known as: Eliquis
Apixaban

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Undergoing elective unilateral TKA
  • Has a body weight ≤130 kg at screening visit
  • 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
  • Is in good health based on laboratory safety testing obtained during the screening period as described in the protocol

You may not qualify if:

  • 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.
  • History of thromboembolic disease or thrombophilia
  • History of major surgery, including brain, spinal, or ocular, within approximately the past 6 months.
  • History of major trauma within approximately the past 6 months.
  • Hospitalized (\>24 hours) for any reason within 30 days of the screening visit
  • Using the Modification of Diet in Renal Disease equation, has an estimated glomerular filtration rate as described in the protocol

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

Ziekenhuis Oost-Limburg- Campus Sint-Jan

Genk, Limburg, 3600, Belgium

Location

MBAL Heart and Brain Hospital

Pleven, 5800, Bulgaria

Location

Durham Bone and Joint Specialists

Ajax, Ontario, L1S 7K7, Canada

Location

MAV Korhaz es Rendelointezet Szolnok

Szolnok, Jász-Nagykun-Szolnok, 5000, Hungary

Location

Department of Orthopedics, Somogy County Mór Kaposi Teaching Hospital

Kaposvár, 7400, Hungary

Location

Liepaja Regional Hospital

Liepāja, LV3414, Latvia

Location

Vidzemes Hospital

Riga, LV-1002, Latvia

Location

Riga's 2nd Hospital

Riga, LV-1004, Latvia

Location

Hospital of Traumatology and Orthopaedics

Riga, LV1005, Latvia

Location

Lietuvos Sveikatos Mokslu Universiteto Ligonine Kauno Klinik

Kaunas, Kaunas County, LT-50009, Lithuania

Location

Klaipeda University Hospital

Klaipėda, Klaipėda County, LT-92288, Lithuania

Location

Lietuvos Sveikatos Mokslu Universiteto Kauno Ligoninė

Kaunas, LT-44320, Lithuania

Location

Specjalistyczny Szpital im. E. Szczeklika w Tarnowie

Tarnów, Lesser Poland Voivodeship, 33-100, Poland

Location

SP ZOZ Centralny Szpital Kliniczny UM w Lodzi

Lodz, 90-153, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie

Lublin, 20-954, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Radzyniu Podlaskim

Radzyń Podlaski, 21-300, Poland

Location

Related Publications (1)

  • 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.

    PMID: 41218619DERIVED

Related Links

MeSH Terms

Conditions

Venous ThromboembolismVenous Thrombosis

Interventions

Enoxaparinapixaban

Condition Hierarchy (Ancestors)

ThromboembolismEmbolism and ThrombosisVascular DiseasesCardiovascular DiseasesThrombosis

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-WeightHeparinGlycosaminoglycansPolysaccharidesCarbohydrates

Results Point of Contact

Title
Clinical Trials Administrator
Organization
Regeneron Pharmaceuticals, Inc.
clinicaltrials@regeneron.com
844-734-6643

Study Officials

  • Clinical Trial Management

    Regeneron Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 8, 2022

First Posted

November 16, 2022

Study Start

May 24, 2023

Primary Completion

May 27, 2024

Study Completion

May 27, 2024

Last Updated

August 29, 2025

Results First Posted

July 16, 2025

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will share

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
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.
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
More information

Locations

LI(3)PL(4)BU(1)CA(1)BE(1)HU(2)LA(4)