A Study to Evaluate the Safety and Efficacy of Intravenous JNJ-64179375 Versus Oral Apixaban in Participants Undergoing Elective Total Knee Replacement Surgery
Condition: VTE Prophylaxis With Anticoagulation After Total Knee Replacement Surgery
Intervention: JNJ-64179375 0.3 mg/kg; JNJ-64179375 0.6 mg/kg; JNJ-64179375 1.2 mg/kg; JNJ-64179375 (Dose to be Determined); JNJ-64179375 A mg/kg; JNJ-64179375 B mg/kg; JNJ-64179375 C mg/kg; JNJ-64179375 D mg/kg; Placebo JNJ-64179375; Apixaban placebo; Apixaban 2.5 mg
Intervention description: 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.
Intervention MeSH terms: Apixaban
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double Blinded
Masking: Double (Participant, Investigator)
Enrollment: 308.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No

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).
    

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