Background
Coagulation factor
XI
(
FXI
) contributes to the development of thrombosis but appears to play only a minor role in hemostasis and is therefore an attractive anticoagulant drug target.
Objectives
To evaluate the safety, pharmacodynamic, and pharmacokinetic properties of
BAY
1213790, a fully human immunoglobulin (Ig) G1 antibody targeting activated coagulation
FXI
(
FXI
a), in healthy men.
Methods
In this phase 1, single‐blind, parallel‐group, placebo‐controlled, dose‐escalation study, 83 healthy Caucasian men were randomized 4:1 to receive a single 60‐minute intravenous infusion of
BAY
1213790 (0.015‐10 mg/kg) or placebo. Adverse events, pharmacodynamic parameters (including activated partial thromboplastin time [
aPTT
]) and pharmacokinetic parameters were determined. Volunteers were followed up for 150 days.
Results
BAY
1213790 demonstrated favorable safety and tolerability; there were no observed cases of bleeding or clinically relevant antidrug antibody formation. One volunteer (1.2%) experienced an infusion reaction. Following intravenous administration of
BAY
1213790, dose‐dependent increases in
aPTT
(maximal mean increase relative to baseline: 1.85 [conventional method] and 2.17 [kaolin‐triggered method]) and rotational thromboelastometry whole blood clotting time were observed, as well as dose‐dependent reductions in
FXI
activity. Bleeding times did not increase following administration of
BAY
1213790 and were similar for all dose cohorts, including placebo. Measurable and dose‐dependent increases in systemic exposure were detected for all doses of
BAY
1213790 of 0.06 mg/kg or higher.
Conclusions
Based on these safety, pharmacodynamic, and pharmacokinetic results, further evaluation of
BAY
1213790 in patients with, or at risk of, thrombosis is warranted.