Single intravenous administration of TB-402 for the prophylaxis of venous thromboembolism after total knee replacement: A dose-escalating, randomized, controlled trial

Abstract

Background:TB-402 is a novel anticoagulant monoclonal antibody with a prolonged antithrombotic effect resulting from its partial factor (F)VIII inhibition and long half-life. We evaluated the efficacy and safety of a single administration of TB-402 for the prevention of venous thromboembolism (VTE) after total knee replacement (TKR). Patients and methods:This was a phase II, dose-escalating, randomized, enoxaparin-controlled, open-label study. Patients were post-operatively assigned to a single dose of TB-402 (0.3, 0.6 or 1.2mgkg-1) or enoxaparin 40mg for at least 10days (n=75 per group; 3:1TB-402 to enoxaparin). The primary efficacy outcome was total VTE defined as asymptomatic deep vein thrombosis (DVT) detected by bilateral venography and symptomatic VTE by day 7 to 11. The principal safety outcome was the incidence of major bleeding and clinically relevant non-major bleeding. Results:Total VTE was lower in all TB-402 groups compared with enoxaparin: 16.7%(95% CI 9.8-26.9), 23.9%(95% CI 15.3-35.3), 24.1%(95% CI 16.0-34.5) and 39.0%(95% CI 28.8-50.1) for TB-402 0.3, 0.6, 1.2mgkg-1 and enoxaparin, respectively (P=0.003 for TB-402 0.3mgkg-1 vs. enoxaparin). The incidence of total VTE in the pooled TB-402 groups was 21.6% (95%CI 16.6-27.5), an absolute risk reduction vs. enoxaparin of 17.4% (95% CI 5.2-29.6). Major or clinically relevant non-major bleeding was observed in 3/75(4.0%), 4/74(5.4%), 7/87(8.0%) and 3/79(3.8%) patients for TB-402 0.3, 0.6, 1.2mgkg-1 and enoxaparin, respectively. Conclusions:TB-402, as a single post-operative administration, was associated with a lower rate of VTE in all doses tested, compared with enoxaparin. The incidence of major and clinically relevant non-major bleeding was similar to enoxaparin 40mg for TB-402 0.3 and 0.6mgkg-1. © 2011 International Society on Thrombosis and Haemostasis.