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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
308
JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenous (IV) infusion as a single dose on Day 1.
JNJ-64179375 0.6 mg/kg IV infusion as a single dose on Day 1.
JNJ-64179375 1.2 mg/kg IV infusion as a single dose on Day 1.
JNJ-64179375 IV infusion (Dose to be determined) as a single dose on Day 1.
JNJ-64179375 Dose A mg/kg IV as a single dose on Day 1.
JNJ-64179375 Dose B mg/kg IV as a single dose on Day 1.
JNJ-64179375 Dose C mg/kg IV as a single dose on Day 1.
JNJ-64179375 Dose D mg/kg IV as a single dose on Day 1.
Matching JNJ-64179375 placebo (normal saline) administered as IV infusion as a single dose on Day 1.
Matching apixaban placebo administered orally twice a day for 10 to 14 days.
Apixaban 2.5 mg administered orally twice a day for 10 to 14 days.
Arizona Research Center
Phoenix, Arizona, United States
Harbor-UCLA Medical Center
Torrance, California, United States
Denver Metro Orthopedics, PC
Englewood, Colorado, United States
Florida Research Associates, LLC
DeLand, Florida, United States
Avanza research
Pensacola, Florida, United States
Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated)
Number of participants with treatment-emergent bleeding events (BE) (adjudicated by CEC) were reported. Bleeding event was defined as the composite of major, clinically relevant nonmajor (CRNM), and minimal bleeding events assessed through the Day 10 to 14.
Time frame: Up to Day 10 to 14 (visit observation period)
Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated)
Number of participants with total VTE were reported. Total VTE was defined as the composite of CEC-adjudicated 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 assessed through the Day 10 to 14 visit. 1 participant had an asymptomatic distal clot in the non-operated leg which is not counted in the Total VTE and 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
Time frame: Up to Day 10 to 14 (visit observation period)
Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated)
Number of participants with composite of major and CRNM bleeding events (adjudicated by CEC) were reported. Major Bleeding: Fatal bleeding; Bleeding that is symptomatic and occurs in critical area/organ and/or; Extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma.
Time frame: Up to Day 10 to 14 (visit observation period)
Number of Participants With Major Bleeding Event (CEC-adjudicated)
Number of participants with major bleeding events (BE) (adjudicated by CEC) were reported. Major Bleeding: Fatal bleeding; Bleeding that is symptomatic and occurs in critical area/organ and/or; Extrasurgical site bleeding causing fall in hemoglobin (Hb) level of 20 grams per liter (g/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability.
Time frame: Up to Day 10 to 14 (visit observation period)
Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated)
Number of participants with CRNM bleeding events (adjudicated by CEC) were reported. CRNM bleeding was defined as acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major bleeding event and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma.
Time frame: Up to Day 10 to 14 (visit observation period)
Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated)
Number of participants with major bleeding or CRNM bleeding events (adjudicated by CEC) were reported. Major Bleeding: Fatal bleeding; Bleeding that is symptomatic and occurs in critical area/organ and/or; Extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma.
Time frame: Up to Day 10 and 14 (visit observation period)
Number of Participants With Minimal Bleeding Events (CEC-adjudicated)
Number of participants with minimal bleeding events (adjudicated by CEC) were reported. Minimal bleeding event was defined as any bleeding event not met major or CRNM criteria.
Time frame: Up to Day 10 to 14 (visit observation period)
Number of Participants With Major VTE (CEC-adjudicated)
Number of participants with major VTE (adjudicated by CEC) were reported. Major VTE was defined as a composite of proximal DVT (asymptomatic confirmed by venography or objectively confirmed symptomatic), nonfatal PE, or any death. 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
Time frame: Up to Day 10 to 14 (visit observation period)
Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated)
Number of participants with proximal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
Time frame: Up to Day 10 to 14 (visit observation period)
Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
Number of participants with nonfatal PE (adjudicated by CEC) were reported.
Time frame: Up to Day 10 to 14 (visit observation period)
Number of Participants With Death (CEC-adjudicated)
Number of participants with death (adjudicated by CEC) were reported.
Time frame: Up to Day 10 to 14 (visit observation period)
Number of Participants With Proximal and Distal DVT (CEC-adjudicated)
Number of participants with proximal and distal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
Time frame: Up to Day 10 to 14 (visit observation period)
Number of Participants With Distal DVT (CEC-adjudicated)
Number of participants with distal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
Time frame: Up to Day 10 to 14 (visit observation period)
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University Orthopedic and Joint Replacement Center
Tamarac, Florida, United States
Memorial Hermann Memorial City Medical Center
Houston, Texas, United States
Hospital Italiano de Buenos Aires
Caba, Argentina
Clínica Adventista Belgrano
CABA, Argentina
Hospital San Roque
Córdoba, Argentina
...and 93 more locations