Abstract 11892: Safety and Pharmacokinetics of a Novel Formulation of Human Apolipoprotein A-I (CSL112) in Healthy Subjects: Results of a Placebo-Controlled, Randomized Multiple Ascending Dose Study
CSL112 is a novel formulation of apolipoprotein (apo) A-I, the active component of HDL, purified from human plasma and reconstituted to form HDL particles suitable for IV infusion. CSL112 resembles nascent HDL and the potential for cardioprotection is being investigated in acute coronary syndromes. To evaluate its safety profile and pharmacokinetics (PK), repeat doses of CSL112 were administered intravenously to healthy subjects in a randomized, placebo-controlled, ascending dose study (NCT number: NCT01281774). Three dose regimens were studied: Group 1: four once-weekly infusions of 3.4 g, Group 2: four once-weekly infusions of 6.8 g, Group 3: eight twice-weekly infusions of 3.4 g. Subjects (N=36) were randomized to CSL112 or placebo (3:1, respectively). Concentrations of apoA-I were shown to peak near the end of infusion and then decline in a biphasic manner. Approximately dose-proportional increases in apoA-I were observed when the CSL112 dose was increased. There were no treatment-emergent serious adverse events reported during the study. Overall, a similar proportion of subjects in the placebo group and CSL112 treatment groups reported at least 1 adverse event (AE); none were reported as study product-related. The most common AE reported was vessel puncture site hematoma (18/36 subjects, 50%), which was reported by similar proportions of subjects administered CSL112 or placebo. In the CSL112 treatment group, no clinically significant abnormalities were observed in serum biochemistry, hematology and urine parameters. In addition, there were no remarkable changes seen in platelet function, vital signs, or ECG that were associated with CSL112 treatment. There was no evidence of immunogenicity to CSL112. This first clinical trial evaluating repeat dosing of CSL112 demonstrated that once- or twice-weekly infusions in healthy subjects had acceptable safety and PK profiles that are sufficiently robust to warrant further testing in patients.
- © 2012 by American Heart Association, Inc.