A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of a First-in-Human Engineered Cationic Peptide, PLG0206, Intravenously Administered in Healthy Subjects.

In this first-in-human study, PLG0206, a novel engineered cationic antimicrobial peptide, was evaluated for safety, tolerability, and pharmacokinetics (PK) when intravenously (i.v.) administered as a single dose to healthy subjects. Six cohorts of 8 subjects each received escalating single i.v. infusions of PLG0206 at 0.05, 0.125, 0.25, 0.5, or 1 mg/kg dose or placebo over 1 to 4 h. Subjects were randomized to receive either PLG0206 (6 per cohort) or placebo (2 per cohort). Serial pharmacokinetic samples were taken prior to infusion and up to 48 h postinfusion. Safety and tolerability were assessed throughout the study. The demographic characteristics of subjects were comparable between those treated with PLG0206 and placebo and between dose groups. The incidence of treatment-emergent adverse events (TEAE) related to PLG0206 was low, and most events were mild in severity and were similar between the PLG0206 treatment and placebo groups. The most common adverse events reported for PLG0206 were infusion-related reactions, which were mitigated with increasing infusion time and volume. There were no severe adverse events (SAEs), life-threatening events, or deaths throughout the study. i.v. PLG0206 exhibited linear pharmacokinetics over the dose range of 0.05 to 1.0 mg/kg. The median terminal half-life () ranged from 7.37 to 19.97 h. Following a single i.v. infusion to healthy subjects, PLG0206 was safe and well tolerated and exhibited linear PK at doses ranging from 0.05 to 1 mg/kg. These findings support the ongoing development of i.v. PLG0206 as an antimicrobial agent.