A Phase 1, Safety and Pharmacokinetic Study of CSL312 in Healthy Subjects

This is a single centre, randomised, double-blind phase 1 study to assess the safety, tolerability and pharmacokinetics (PK) of single ascending doses of intravenous (IV) or subcutaneous (SC) administrations of CSL312 in healthy subjects. Subjects can participate in only 1 dose group and will be randomly assigned to receive a single dose of either CSL312 or placebo by IV infusion or SC injection (abdomen). Study drugs will be administered at the study site by study staff. CSL312 is a fully human recombinant anti-FXIIa antibody (Factor XIIa antagonist monoclonal antibody), solution for injection. The dose and infusion volume will be based upon the subject's body weight and the allowable drug concentration. Dose escalation requires Safety Review Committee review of available blinded safety, tolerability, PK and selected Pharmacodynamic (PD) data. Eight groups of 6 subjects are planned; 5 groups for IV administration and 3 groups for SC administration. Dosing and initial dose escalation will begin with the IV groups, and upon reaching the third IV group, the study will progress to the SC groups. Dose escalation within the IV and SC groups will then progress in parallel with the SC groups staggered to start after initial dosing in their respective IV groups. For all IV groups and the first SC group, 2 sentinel subjects per group will be randomised to receive CSL312 or placebo in a 1:1 ratio, and the remaining 4 subjects per group will be randomised to receive CSL312 or placebo in a 3:1 ratio.