Background & Aims
Myrcludex B is a first-in-class compound, which blocks entry of hepatitis B and D virus into hepatocytes in vitro and in animal models. Based on the required preclinical data we aimed to translate this compound into the first application in humans.
Single ascending doses of myrcludex B, a 47 amino acid peptide, were administered up to 20 mg intravenously and 10 mg subcutaneously in a prospective open first-in-human, phase I clinical trial to 36 healthy volunteers. Safety, tolerability and plasma concentrations of myrcludex B were assessed and a pharmacokinetic model was derived.
Myrcludex B was well tolerated and no serious or relevant adverse events representing off-target effects, and no immunogenic effects were observed up to the highest applied dose of 20 mg (intravenously). Myrcludex B showed dose-dependent pharmacokinetics, best described by a 2-compartment target-mediated drug disposition model. Bioavailability of the subcutaneous application was large (85%). Interindividual variability was moderate. The pharmacokinetic model suggested that subcutaneous doses of 10 mg and above reach a target saturation of over 80% for at least 15 hours.
Myrcludex B showed excellent tolerability up to high doses and pharmacologic properties followed a 2-compartment target-mediated drug disposition model. These findings are vital for planning of further multiple dose efficacy trials in patients.