NCT03251482

A Study to Evaluate the Safety and Efficacy of Intravenous JNJ-64179375 Versus Oral Apixaban in Participants Undergoing Elective Total Knee Replacement Surgery

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 308 (actual)
• Sponsor: Janssen Research & Development, LLC · Industry
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

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.

Conditions

• VTE Prophylaxis With Anticoagulation After Total Knee Replacement Surgery

Interventions

Type	Name	Description
DRUG	JNJ-64179375 0.3 mg/kg	JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenous (IV) infusion as a single dose on Day 1.
DRUG	JNJ-64179375 0.6 mg/kg	JNJ-64179375 0.6 mg/kg IV infusion as a single dose on Day 1.
DRUG	JNJ-64179375 1.2 mg/kg	JNJ-64179375 1.2 mg/kg IV infusion as a single dose on Day 1.
DRUG	JNJ-64179375 (Dose to be Determined)	JNJ-64179375 IV infusion (Dose to be determined) as a single dose on Day 1.
DRUG	JNJ-64179375 A mg/kg	JNJ-64179375 Dose A mg/kg IV as a single dose on Day 1.
DRUG	JNJ-64179375 B mg/kg	JNJ-64179375 Dose B mg/kg IV as a single dose on Day 1.
DRUG	JNJ-64179375 C mg/kg	JNJ-64179375 Dose C mg/kg IV as a single dose on Day 1.
DRUG	JNJ-64179375 D mg/kg	JNJ-64179375 Dose D mg/kg IV as a single dose on Day 1.
DRUG	Placebo JNJ-64179375	Matching JNJ-64179375 placebo (normal saline) administered as IV infusion as a single dose on Day 1.
DRUG	Apixaban placebo	Matching apixaban placebo administered orally twice a day for 10 to 14 days.
DRUG	Apixaban 2.5 mg	Apixaban 2.5 mg administered orally twice a day for 10 to 14 days.

Timeline

• Start date: 2017-11-13
• Primary completion: 2018-11-05
• Completion: 2018-11-05
• First posted: 2017-08-16
• Last updated: 2019-11-25
• Results posted: 2019-11-25

Locations

103 sites across 16 countries: United States, Argentina, Belgium, Brazil, Bulgaria, Canada, Italy, Japan, Latvia, Lithuania, Malaysia, Poland, Russia, Spain, Turkey (Türkiye), Ukraine

Regulatory

• FDA-regulated drug study