A Study of JNJ-70033093 (BMS-986177) Versus Subcutaneous Enoxaparin in Participants Undergoing Elective Total Knee Replacement Surgery

NCT ID: NCT03891524

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 1242 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-17
• Study Completion Date: 2021-04-06

Brief Summary

The purpose of this study is to determine the efficacy of JNJ-70033093 in preventing total venous thromboembolism (VTE) events (proximal and/or distal deep vein thrombosis [DVT] [asymptomatic confirmed by venography assessment or objectively confirmed symptomatic], nonfatal pulmonary embolism [PE], or any death) during the treatment period.

Detailed Description

JNJ-70033093 is an oral anticoagulant for prevention and treatment of thromboembolic events (for example, VTE) that binds and inhibits activated form of human coagulation Factor XI (FXIa) with high affinity and selectivity. The study will consist of 3 phases: up to 30-day screening phase before total knee replacement (TKR) surgery, 10 to14 day postoperative dosing phase, and 4-week follow-up phase. The hypothesis of this study is JNJ-70033093 reduces risk of total VTE during treatment period. The total duration of participation following randomization will be approximately 6 weeks. Efficacy evaluations include unilateral venography assessment of operated leg and assessments of symptomatic DVT, PE, or death. Safety evaluation includes adverse events, clinical laboratory tests, and physical examinations. The safety and efficacy will be monitored throughout the study.

Conditions

Arthroplasty, Replacement, Knee

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Group A: JNJ-70033093 25 mg + Placebo BID

Participants will receive JNJ-70033093 25 milligram (mg) (1\*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days.

Group Type: EXPERIMENTAL

JNJ-70033093 25 mg

Intervention Type: DRUG

Participants will receive JNJ-70033093 25 mg (1\*25 mg capsule) BID (in Group A) or once daily (in Group E), orally for 10 to 14 postoperative days.

Placebo

Intervention Type: DRUG

Participants will receive placebo matching to JNJ-70033093, orally.

Group B: JNJ-70033093 50 mg BID

Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days.

Group Type: EXPERIMENTAL

JNJ-70033093 50 mg

Intervention Type: DRUG

Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days.

Group C: JNJ-70033093 100 mg + Placebo BID

Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days.

Group Type: EXPERIMENTAL

JNJ-70033093 100 mg

Intervention Type: DRUG

Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) BID, orally for 10 to 14 postoperative days.

Placebo

Intervention Type: DRUG

Participants will receive placebo matching to JNJ-70033093, orally.

Group D: JNJ-70033093 200 mg BID

Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID orally for 10 to 14 postoperative days.

Group Type: EXPERIMENTAL

JNJ-70033093 200 mg

Intervention Type: DRUG

Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID (in Group D) or once daily (in Group F), orally for 10 to 14 postoperative days.

Group E: JNJ-70033093 25 mg Once Daily + Placebo

Participants will receive JNJ-70033093 25 mg (1\*25 mg capsule) once daily and 1 placebo capsule in the morning and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

Group Type: EXPERIMENTAL

JNJ-70033093 25 mg

Intervention Type: DRUG

Participants will receive JNJ-70033093 25 mg (1\*25 mg capsule) BID (in Group A) or once daily (in Group E), orally for 10 to 14 postoperative days.

Placebo

Intervention Type: DRUG

Participants will receive placebo matching to JNJ-70033093, orally.

Group F: JNJ-70033093 200 mg Once Daily + Placebo

Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

Group Type: EXPERIMENTAL

JNJ-70033093 200 mg

Intervention Type: DRUG

Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID (in Group D) or once daily (in Group F), orally for 10 to 14 postoperative days.

Placebo

Intervention Type: DRUG

Participants will receive placebo matching to JNJ-70033093, orally.

Group G: JNJ-70033093 50 mg once daily + Placebo

Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

Group Type: EXPERIMENTAL

JNJ-70033093 50 mg

Intervention Type: DRUG

Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days.

Placebo

Intervention Type: DRUG

Participants will receive placebo matching to JNJ-70033093, orally.

Group I: Enoxaparin 40 mg Once Daily

Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.

Group Type: ACTIVE_COMPARATOR

Enoxaparin 40 mg

Intervention Type: DRUG

Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.

Interventions

JNJ-70033093 25 mg

Participants will receive JNJ-70033093 25 mg (1\*25 mg capsule) BID (in Group A) or once daily (in Group E), orally for 10 to 14 postoperative days.

Intervention Type: DRUG

JNJ-70033093 50 mg

Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days.

Intervention Type: DRUG

JNJ-70033093 100 mg

Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) BID, orally for 10 to 14 postoperative days.

Intervention Type: DRUG

JNJ-70033093 200 mg

Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID (in Group D) or once daily (in Group F), orally for 10 to 14 postoperative days.

Intervention Type: DRUG

Placebo

Participants will receive placebo matching to JNJ-70033093, orally.

Intervention Type: DRUG

Enoxaparin 40 mg

Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.

Intervention Type: DRUG

Other Intervention Names

BMS-986177; BMS-986177; BMS-986177; BMS-986177

Eligibility Criteria

Inclusion Criteria

• Medically stable and appropriate for anticoagulant prophylaxis as determined by the investigator on the basis of physical examination, medical history, and vital signs performed as part of screening for elective total knee replacement (TKR) surgery
• Medically stable and appropriate for anticoagulant prophylaxis on the basis of clinical laboratory tests performed as part of local standard-of-care as part of screening for elective TKR surgery
• Has plans to undergo an elective primary unilateral TKR surgery
• A woman must be- a) Not of childbearing potential; b) Of childbearing potential and practicing a highly effective method of contraception (failure rate of less than [<]1 percent [%] per year when used consistently and correctly) and agrees to remain on a highly effective method for the duration of study drug with JNJ-70033093 plus 5 half-lives of study drug plus 30 days (duration of ovulatory cycle) for a total of 34 days after the completion of treatment, pregnancy testing (serum or urine) prior to the first dose of study drug
• Willing and able to adhere to the lifestyle restrictions specified in this protocol

Exclusion Criteria

• History of any condition for which the use of low molecular-weight heparin (LMWH) is not recommended in the opinion of the investigator (for example, previous allergic reaction, creatinine clearance <30 milliliter per minute [mL/minute])
• History of severe hepatic impairment
• Planned bilateral revision or unicompartmental procedure
• Unable to undergo venography (for example, due to contrast agent allergy, poor venous access, or impaired renal function that would increase the risk of contrast-induced nephropathy
• Known previous pulmonary embolism (PE) or deep vein thrombosis (DVT) in either lower extremity

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Central Research Associates, Inc.

Birmingham, Alabama, United States

Arizona Research Center

Phoenix, Arizona, United States

Bowen Hefley Orthopedics

Little Rock, Arkansas, United States

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, United States

Denver Metro Orthopedics, PC

Englewood, Colorado, United States

DMI Research

Pinellas Park, Florida, United States

Gulfcoast Research Institute

Sarasota, Florida, United States

University Orthopedic and Joint Replacement Center

Tamarac, Florida, United States

Memorial Hermann Memorial City Medical Center

Houston, Texas, United States

Hospital Britanico de Buenos Aires

Buenos Aires, , Argentina

Clinica Adventista Belgrano

CABA, , Argentina

Hospital San Roque

Córdoba, , Argentina

Clínica Chutro

Córdoba, , Argentina

Hospital Italiano La Plata

La Plata, , Argentina

Instituto de Investigaciones Clinicas Rosario

Rosario, , Argentina

Sanatorio Corporación Médica de General San Martín

San Martín, , Argentina

ZNA Middelheim

Antwerp, , Belgium

Ziekenhuis Oost-Limburg

Genk, , Belgium

Jessa Ziekenhuis

Hasselt, , Belgium

ZNA Jan Palfijn

Merksem, , Belgium

Hospital Sao Francisco de Assis

Belo Horizonte, , Brazil

Hospital e Maternidade Dr Christovao da Gama S.A

Santo André, , Brazil

Hospital Estadual Mario covas

Santo André, , Brazil

University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski

Pleven, , Bulgaria

Acibadem City Clinic Tokuda Hospital

Sofa, , Bulgaria

University Multiprofile Hospital Sofiamed Sofia

Sofia, , Bulgaria

MHAT Tzaritza Joanna

Sofia, , Bulgaria

Medical Center - Medical Complex BEROE EOOD

Stara Zagora, , Bulgaria

Lakeridge Health

Ajax, Ontario, Canada

Hamilton Health Sciences Corporation

Hamilton, Ontario, Canada

The Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Medical Investigative and Clinical Evaluation Inc

Windsor, Ontario, Canada

General Hospital of Attiki 'KAT'

Kifissia, , Greece

General Hospital of Nea Ionia 'Konstantopoulio'

Nea Ionia, , Greece

University General Hospital of Rio Patras

Pátrai, , Greece

Papageorgiou General Hospital

Thessaloniki, , Greece

Semmelweis Egyetem

Budapest, , Hungary

Debreceni Egyetem

Debrecen, , Hungary

Petz Aladar Megyei Oktato Korhaz

Gyõr, , Hungary

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvár, , Hungary

Bacs-kiskun Megyei Korhaz

Kecskemét, , Hungary

Szegedi Tudomanyegyetem

Szeged, , Hungary

Fejer Varmegyei Szent Gyorgy Egyetemi Oktatokorhaz

Székesfehérvár, , Hungary

MAV Korhaz es Rendelointezet

Szolnok, , Hungary

Rambam Medical Center

Haifa, , Israel

Carmel Medical Center

Haifa, , Israel

Meir Medical Center

Kfar Saba, , Israel

Kaplan Medical Center

Rehovot, , Israel

Cliniche Humanitas Gavazzeni

Bergamo, , Italy

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, , Italy

Istituto Ortopedico Rizzoli

Bologna, , Italy

Policlinico S. Matteo

Pavia, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

A.O.U. Città della Salute e della Scienza

Torino, , Italy

Matsudo City General Hospital

Chiba, , Japan

Hakodate Goryoukaku Hospital

Hakodate, , Japan

Japanese Red Cross Hamamatsu Hospital

Hamamatsu, , Japan

Itami City Hospital

Itami-shi, , Japan

Yonemori Hospital

Kagoshima, , Japan

Japan Community Health care Organization Kyushu Hospital

Kitakyushu-shi, , Japan

Marunouchi Hospital

Matsumoto, , Japan

Chubu Rosai Hospital

Nagoya, , Japan

Juntendo University Nerima Hospital

Nerima-Ku, , Japan

National Hospital Organization Okayama Medical Center

Okayama, , Japan

Yuuai Medical Center

Okinawa, , Japan

Japan Community Health Care Organization Saitama Medical Center

Saitama, , Japan

Saitama City Hospital

Saitama-shi, , Japan

Nagano Prefectural Shinshu Medical Center

Suzaka, , Japan

Juntendo University Hospital

Tokyo, , Japan

Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Bielsku Podlaskim Oddzial Urazowo Ortopedyczny

Bielsk Podlaski, , Poland

Szpital Ogolny im. W. Ginela, Oddzial Urazowo-Ortopedyczny

Grajewo, , Poland

Wojewodzki Szpital Zespolony w Kielcach, Klinika Chirurgii Ortopedyczno-Urazowej

Kielce, , Poland

Oddzial Ortopedii i Traumatologii Narzadu Ruchu Szpital Specjalistyczny im Ludwika Rydygiera

Krakow, , Poland

CSK UM Klinika Ortopedii

Lodz, , Poland

Oddzial Urazowo-Ortopedyczny Wojewodzki Szpital Specjalistyczny

Lublin, , Poland

Oddzial Ortopedii Specjalistyczny Szpital im. E.Szczeklika

Tarnów, , Poland

Oddzial Chirurgii Urazowej iOrtopedycznej Wojewodzki Szpital Brodnowski SPZOZ

Warsaw, , Poland

Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, , Poland

Centro Hospitalar do Baixo Vouga - Hospital Infante Dom Pedro

Aveiro, , Portugal

Hosp de Cascais

Cascais, , Portugal

H. Santo António - Centro Hospitalar do Porto

Porto, , Portugal

CHS - Hosp. Orto. Sant'Iago do Outao

Setúbal, , Portugal

ULSAM, EPE - Hospital de Santa Luzia

Viana do Castelo, , Portugal

National Medical Research Center of Traumatology and Orthopaedics n.a. G.A. Ilizarov

Kurgan, , Russia

Private Healthcare Institution 'Clinical Hospital 'RZD-Medcine' n.a. N.A.Semashko'

Moscow, , Russia

Privolzhsky Regional Medical Center of Federal Medical and Biological Agency

Nizhny Novgorod, , Russia

National medical research center of Traumatology and Orthopaedics n.a. R.R.Vreden

Saint Petersburg, , Russia

State Healthcare Institution Samara Regional Clinical Hospital named after V.D.Seredavin

Samara, , Russia

Smolensk Federal Center of Traumatology, Orthopedics and Endoprothesis Replacement

Smolensk, , Russia

Sochi City Hospital #4

Sochi, , Russia

Steve Biko Academic Hospital

Pretoria, , South Africa

Clinical Project Research SA

Worcester, , South Africa

Hosp. Univ. Fundacion Alcorcon

Alcorcón, , Spain

Hosp. Univ. Germans Trias I Pujol

Badalona, , Spain

Hosp Clinic de Barcelona

Barcelona, , Spain

Hosp. Univ. de Bellvitge

Barcelona, , Spain

Hosp Univ Vall D Hebron

Barcelona, , Spain

Complejo Hospitalario de Jaen

Jaén, , Spain

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Hosp. Univ. La Paz

Madrid, , Spain

Corporacio Sanitari Parc Tauli

Sabadell, , Spain

Hosp. Clinico Univ. de Valencia

Valencia, , Spain

Hosp. Univ. I Politecni La Fe

Valencia, , Spain

Adana City Hospital

Adana, , Turkey (Türkiye)

Diskapi Yildırim Beyazid Training and Research Hospital

Ankara, , Turkey (Türkiye)

Yıldırım Beyazıt University Yenimahalle Training and Research Hospital

Ankara, , Turkey (Türkiye)

Antalya Training And Research Hospital

Antalya, , Turkey (Türkiye)

Bakirkoy Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Sisli Etfal Research Training Hospital

Istanbul, , Turkey (Türkiye)

Izmir Tepecik Training and Research Hospital

Izmir, , Turkey (Türkiye)

Ivano-Frankivsk Regional Clinical Hospital

Ivano-Frankivsk, , Ukraine

Institute of Spine and JointPathology named after Prof.Sytenko of NationalAcademy of MedicalSciences

Kharkiv, , Ukraine

Municipal Institution of Health Care 'Kharkiv Regional Clinical Traumatology Hospital'

Kharkiv, , Ukraine

Kyiv Regional Clinical Hospital

Kyiv, , Ukraine

Communal Institution of Lviv Regional Council 'Lypa Lviv Regional Hospital'

Lviv-Vynnyky, , Ukraine

Municipal Non-profit Enterprise 'Odesa Regional Clinical Hospital' Odesa Regional Council

Odesa, , Ukraine

Vinnytsya Regional Clinical Hospital named after M.I.Pirogov

Vinnytsia, , Ukraine

Countries

United States; Argentina; Belgium; Brazil; Bulgaria; Canada; Greece; Hungary; Israel; Italy; Japan; Poland; Portugal; Russia; South Africa; Spain; Turkey (Türkiye); Ukraine

References

Whiteson HZ, Frishman WH. Factor XI/XIa Inhibitors: A New Approach to Anticoagulation. Cardiol Rev. 2025 Jul-Aug 01;33(4):306-311. doi: 10.1097/CRD.0000000000000624. Epub 2023 Dec 1.

Reference Type: DERIVED

PMID: 38038437 (View on PubMed)

Weitz JI, Strony J, Ageno W, Gailani D, Hylek EM, Lassen MR, Mahaffey KW, Notani RS, Roberts R, Segers A, Raskob GE; AXIOMATIC-TKR Investigators. Milvexian for the Prevention of Venous Thromboembolism. N Engl J Med. 2021 Dec 2;385(23):2161-2172. doi: 10.1056/NEJMoa2113194. Epub 2021 Nov 15.

Reference Type: DERIVED

PMID: 34780683 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

70033093THR2001

Identifier Type: OTHER

Identifier Source: secondary_id

2018-004237-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108600

Identifier Type: -

Identifier Source: org_study_id