Single Intravenous Administration of TB-402 for the Prophylaxis of Venous Thromboembolic Events (VTE) After Total Knee Replacement Surgery

Single Intravenous Administration of TB-402 for the Prophylaxis of Venous Thromboembolic Events (VTE) After Total Knee Replacement Surgery: A Dose-Escalating, Multicenter, Randomised, Active- Controlled Open Label Study

The purpose of this study is to evaluate the safety and efficacy of a single administration of TB-402 for the prevention of VTE in patients undergoing knee replacement surgery.

Currently available anticoagulant therapies for the prevention of VTE include low molecular weight heparins, pentasaccharides and vitamin K antagonists, all of which have inherent limitations(1-3).

Improved anticoagulant agents are therefore required(4). A novel antithrombotic agent requires demonstration of both efficacy and safety in relevant populations. Phase II studies are frequently performed in patients undergoing total hip replacement and/or total knee replacement because of the high and well documented incidence of deep vein thrombosis in the absence of adequate thromboprophylaxis(5-7).

In this study, we assess the safety and efficacy of TB-402, a novel antithrombotic agent that partially inhibits factor VIII, in the prevention of VTE in patients undergoing total knee replacement surgery.

Inclusion Criteria:

• Male or female patients aged > 18 and < 80 years old
• Female patients should be post menopausal
• Patients undergoing primary elective total knee replacement surgery
• Written informed consent obtained from the patient (or a legally acceptable representative) prior to inclusion in the study
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

Exclusion Criteria:

• Body weight < 50 kg or > 100 kg
• Patients undergoing a hemiarthroplasty, surface repair or revisionary surgery of the knee
• Confirmed symptomatic deep vein thrombosis or pulmonary embolism within the past year
• Anticipated use of indwelling intrathecal or epidural catheter for more than 4 h after surgery or during the entire study
• Uncontrolled hypertension (SBP>160 mm Hg or DBP > 100 mm Hg)
• History of intracranial or intraocular bleeding. History of gastrointestinal and/or endoscopically verified ulcer disease within the past year