Clinical trial NCT03251482: A Study to Evaluate the Safety and Efficacy of Intravenous JNJ-64179375 Versus Oral Apixaban in Participants Undergoing Elective Total Knee Replacement Surgery
Official title: A Randomized, Double-blind, Double-dummy, Multicenter, Adaptive Design, Dose Escalation (Part 1) and Dose-Response (Part 2) Study to Evaluate the Safety and Efficacy of Intravenous JNJ-64179375 Versus Oral Apixaban in Subjects Undergoing Elective Total Knee Replacement Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: VTE Prophylaxis With Anticoagulation After Total Knee Replacement Surgery
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-08-16
Enrollment: 308
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double Blinded
Primary purpose: PREVENTION

Brief summary: The primary purpose of Part 1 in this study is to assess the safety and tolerability of JNJ-64179375 for each dose level for dose escalation and any bleeding events (the composite of major, clinically relevant non-major, and minimal bleeding events) for the selection of doses for Part 2. The primary purpose of Part 2 is to assess the efficacy dose response of JNJ-64179375 for the prevention of total venous thromboembolism (VTE) (proximal and/or distal deep vein thrombosis \[DVT\] \[asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic\], nonfatal pulmonary embolism \[PE\], or any death).

Detailed description: This study has 2 parts, dose escalation and dose-response evaluation, and will be conducted in participants undergoing primary unilateral elective Total Knee Replacement (TKR) surgery. Participants will participate in either Part 1 or Part 2 of study only. The study will be conducted in 3 phases: an up to 30-day screening phase before surgery, a 14-day double-blind dosing phase, and a 16-week follow-up phase. Safety evaluations will include monitoring of all nonserious and serious adverse events, clinical laboratory tests, vital signs measurements, and physical examinations. Pharmacokinetics (dense and sparse), pharmacodynamic (PD), health resource utilization, and immunogenicity samples will also be assessed. The total study duration of participant's participation in Part 1 or part 2 after randomization will be approximately 18 weeks.

Eligibility criteria: Inclusion Criteria:

* Weight greater than or equal to (\>=) 40 kg to less than or equal to (\<=) 150 kilogram (kg)
* Medically appropriate for postoperative anticoagulant prophylaxis as determined by the investigator
* Has undergone an elective primary unilateral total knee replacement (TKR)
* Before randomization, a woman must not be of childbearing potential defined as postmenopausal (defined as no menses for 12 months without an alternative medical cause) and/ or permanently sterile (include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy)
* Contraceptive use by men should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies

Exclusion Criteria:

* Any condition for which the use of apixaban is not recommended in the opinion of the investigator
* Bilateral, revision or unicompartmental procedure
* Known or suspected hypersensitivity or intolerance to any biologic medication or known allergies or clinically significant reactions to murine, chimeric, or human proteins, monoclonal antibodies or antibody fragments, or any of the excipients of JNJ-64179375
* Unable to undergo venography
* Known previous deep vein thrombosis (DVT) in either lower extremity

Primary outcomes:
measure: Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated)
timeFrame: Up to Day 10 to 14 (visit observation period)
measure: Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated)
timeFrame: Up to Day 10 to 14 (visit observation period)
Secondary outcomes:
measure: Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated)
timeFrame: Up to Day 10 to 14 (visit observation period)
measure: Number of Participants With Major Bleeding Event (CEC-adjudicated)
timeFrame: Up to Day 10 to 14 (visit observation period)
measure: Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated)
timeFrame: Up to Day 10 to 14 (visit observation period)
measure: Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated)
timeFrame: Up to Day 10 and 14 (visit observation period)
measure: Number of Participants With Minimal Bleeding Events (CEC-adjudicated)
timeFrame: Up to Day 10 to 14 (visit observation period)
measure: Number of Participants With Major VTE (CEC-adjudicated)
timeFrame: Up to Day 10 to 14 (visit observation period)
measure: Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated)
timeFrame: Up to Day 10 to 14 (visit observation period)
measure: Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
timeFrame: Up to Day 10 to 14 (visit observation period)
measure: Number of Participants With Death (CEC-adjudicated)
timeFrame: Up to Day 10 to 14 (visit observation period)
measure: Number of Participants With Proximal and Distal DVT (CEC-adjudicated)
timeFrame: Up to Day 10 to 14 (visit observation period)
measure: Number of Participants With Distal DVT (CEC-adjudicated)
timeFrame: Up to Day 10 to 14 (visit observation period)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Englewood
country: United States
facility: Denver Metro Orthopedics, PC
state: Colorado
city: DeLand
country: United States
facility: Florida Research Associates, LLC
state: Florida
city: Pensacola
country: United States
facility: Avanza research
state: Florida
city: Tamarac
country: United States
facility: University Orthopedic and Joint Replacement Center
state: Florida
city: Houston
country: United States
facility: Memorial Hermann Memorial City Medical Center
state: Texas
city: Caba
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Caba
country: Argentina
facility: Clínica Adventista Belgrano
city: Córdoba
country: Argentina
facility: Hospital San Roque
city: Córdoba
country: Argentina
facility: Clínica Chutro
city: La Plata
country: Argentina
facility: Hospital Italiano La Plata
city: Rosario
country: Argentina
facility: Sanatorio Britanico de Rosario
city: San Miguel
country: Argentina
facility: Sanatorio San Miguel
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Merksem
country: Belgium
facility: ZNA Jan Palfijn
city: Belo Horizonte
country: Brazil
facility: Universidade Federal de Minas Gerais (UFMG) - Faculdade de Medicina
city: Belo Horizonte
country: Brazil
facility: Hospital Sao Francisco de Assis
city: Campinas
country: Brazil
facility: Unicamp - Hospital de Clinicas
city: Londrina
country: Brazil
facility: Uniort.e - Hospital de ortopedia
city: Marilia
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Marília
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
city: Santo André
country: Brazil
facility: Hospital e Maternidade Dr Christovão da Gama
city: Santo André
country: Brazil
facility: Hospital Estadual Mario covas
city: São Paulo
country: Brazil
facility: Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo
city: Russe
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Russe
city: Sofa
country: Bulgaria
facility: Acibadem City Clinic Tokuda Hospital
city: Sofia
country: Bulgaria
facility: Military Medical Academy
city: Ajax
country: Canada
facility: Lakeridge Health Ajax
state: Ontario
city: Kitchener
country: Canada
facility: Source Trial Solutions Inc.
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Research Institute
state: Ontario
city: Bergamo
country: Italy
facility: Cliniche Humanitas Gavazzeni
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: S. Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza
city: Torino
country: Italy
facility: Ospedale Mauriziano (Torino)
city: Chiba
country: Japan
facility: Matsudo City General Hospital
city: Hakodate
country: Japan
facility: Hakodate Goryokaku Hospital
city: Iida-shi
country: Japan
facility: Ritsuzankai Iida Hospital
city: Itami-shi
country: Japan
facility: Itami City Hospital
city: Kagoshima-shi
country: Japan
facility: Yonemori Hospital
city: Kawanuma-Gun
country: Japan
facility: Bange Kousei General Hospital
city: Osaka-shi
country: Japan
facility: Osaka Saiseikai Nakatsu Hospital
city: Osaka
country: Japan
facility: Osaka Rosai Hospital
city: Tokushima-shi
country: Japan
facility: Tokushima Municipal Hospital
city: Tomishiro
country: Japan
facility: Yuaikai Tomishiro Central Hospital
city: Liepaja
country: Latvia
facility: Regional Hospital of Liepaja
city: Riga
country: Latvia
facility: Riga 2nd Hospital
city: Riga
country: Latvia
facility: Hospital of Traumatology and Orthopedics
city: Valmiera
country: Latvia
facility: Vidzemes Hospital
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics
city: Klaipeda
country: Lithuania
facility: Klaipeda University Hospital
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Center
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
city: Miri
country: Malaysia
facility: Hospital Miri
city: Sibu
country: Malaysia
facility: Hospital Sibu
city: Sungai Petani
country: Malaysia
facility: Hospital Sultan Abdul Halim
city: Bialystok
country: Poland
facility: Klinika Ortopedii i Traumatologii UMB
city: Grajewo
country: Poland
facility: Oddzial Ortopedii i Traumatologii - Szpital Ogolny im. W.Ginela
city: Katowice
country: Poland
facility: Klinika Ortopedii Gornoslaskie Centrum Medyczne
city: Krakow
country: Poland
facility: Oddzial Ortopedii i Traumatologii Szpital Specjalistyczny im. L.Rydygiera
city: Krakow
country: Poland
facility: SP ZOZ MSWiA w Krakowie Oddzial Urazowo-Ortopedyczny
city: Lodz
country: Poland
facility: CSK UM Klinika Ortopedii
city: Lublin
country: Poland
facility: Oddzial Urazowo-Ortopedyczny Wojewodzki Szpital Specjalistyczny
city: Poznan
country: Poland
facility: Klinika Ortopedii I Traumatologii,Szpital Kliniczny Ortopedyczno-Rehabilitacyjny UM
city: Tarnow
country: Poland
facility: Oddzial Ortopedii Specjalistyczny Szpital im. E.Szczeklika
city: Warszawa
country: Poland
facility: Oddzial Chirurgii Urazowej iOrtopedycznej,Wojewodzki Szpital Brodnowski, SPZOZ
city: Barnaul
country: Russian Federation
facility: Barnaul Federal Center of Traumatology, Orthopedics and Endoprothesis replacement
city: Kurgan
country: Russian Federation
facility: Russian Ilizarov Scientific Center For Restorative Traumatology And Ortopaedics
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital #1 n.a. N.I.Pirogov
city: Nizhny Novgorod
country: Russian Federation
facility: Privolzhsky Research Medical University of Ministry of Health of Russian Federation
city: Saint-Petersburg
country: Russian Federation
facility: St. Petersburg State Medical Institution City Multifunctional Hospital #2
city: Saint-Petersburg
country: Russian Federation
facility: Russian Research Institute of Traumatology and Orthopaedics n.a.R.R.Vreden
city: Samara
country: Russian Federation
facility: State Healthcare Institution Samara Regional Clinical Hospital named after V.D.Seredavin
city: Yaroslavl
country: Russian Federation
facility: Clinical Emergency Hospital n.a. N.V. Solovyev
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Madrid
country: Spain
facility: Hosp. Clinico San Carlos
city: Madrid
country: Spain
facility: Hosp. Univ. Fund. Jimenez Diaz
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Sabadell
country: Spain
facility: Corporacio Sanitari Parc Tauli
city: Santiago de Compostela
country: Spain
facility: Hosp. Clinico Univ. de Santiago
city: Valencia
country: Spain
facility: Hosp. Univ. I Politecni La Fe
city: Ankara
country: Turkey
facility: Ankara Numune Research and Training Hospital
city: Ankara
country: Turkey
facility: Dışkapı Yıldırım Beyazıd Training and Research Hospital
city: Ankara
country: Turkey
facility: Yıldırım Beyazıt University Yenimahalle Training and Research Hospital
city: Ankara
country: Turkey
facility: Yildirim Beyazit University Medical Faculty Ankara Atatürk Research and Training Hospital
city: Istanbul
country: Turkey
facility: Bakirkoy Training and Research Hospital
city: Istanbul
country: Turkey
facility: Umraniye Training and Research Hospital
city: Izmir
country: Turkey
facility: Izmir Tepecik Training and Research Hospital
city: Cherkasy
country: Ukraine
facility: Municipal Institution Cherkasy Regional Hospital of Cherkasy Regional Council
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Clinical Hospital
city: Kharkiv
country: Ukraine
facility: Institute of Spine and JointPathology named after Prof.Sytenko of NationalAcademy of MedicalSciences
city: Kharkiv
country: Ukraine
facility: Municipal Institution of Health Care 'Kharkiv Regional Clinical Traumatology Hospital'
city: Kyiv
country: Ukraine
facility: Kyiv Regional Clinical Hospital
city: Lviv-Vynnyky
country: Ukraine
facility: Communal Institution of Lviv Regional Council 'Lypa Lviv Regional Hospital'
city: Vinnytsia
country: Ukraine
facility: Vinnytsya Regional Clinical Hospital named after M.I.Pirogov
city: Zaporizhzhia
country: Ukraine
facility: Zaporizhzhia Regional Clinical Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: