Abstract 15084: Safety and Efficacy of Anti-von Willebrand Factor Nanobody® ALX-0081 in Stable Angina Patients Undergoing Percutaneous Coronary Intervention
Introduction: The Nanobody ALX-0081 specifically targets the A1 domain of von Willebrand factor (vWF) and blocks the interaction between vWF and the GPIb receptor on the surface of platelets. ALX-0081 selectively prevents thrombus formation under high shear stress conditions.
Hypothesis: We evaluated the safety, pharmacokinetics and efficacy of ALX-0081 in patients with stable angina undergoing an elective percutaneous coronary intervention. The effect of ALX-0081 on platelet reactivity after clopidogrel treatment was also examined.
Methods: In total, 46 patients receiving a standard antithrombotic regimen (aspirin, heparin and clopidogrel) were included in this randomised, placebo-controlled Phase Ib study. Single and multiple doses of ALX-0081 were administered as 1 hour i.v. infusions. In addition, 22 patients were included in an open-label extension of the study and received i.v. bolus injections (Table 1).
Results: (Table 1) ALX-0081 was safe and well tolerated at all doses, both after i.v. infusion and bolus injection. No excessive adverse events or bleeding complications were noted. Observed reductions of Factor VIII and vWF levels were not considered clinically significant or adverse events. Anti-drug antibodies were not detected up to 30 days after the last injection. A single dose of 6 mg followed by three subsequent doses of 4 mg every 6 hours was established to be the biologically effective dose, resulting in complete inhibition of the biomarker RICO (ristocetin cofactor activity, a measure for vWF mediated platelet aggregation) (P < 0.0001, compared with placebo). Decrease in platelet activity mediated by ALX-0081 was independent of treatment response to clopidrogel.
Conclusion: Collectively, the data from the Phase Ib study and its open-label extension provide proof-of-concept that ALX-0081 is safe, well tolerated and a potent inhibitor of platelet aggregation.
- © 2010 by American Heart Association, Inc.