A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Escalation Study for the Evaluation of the Safety, Tolerability, and Pharmacokinetics of Recombinant Human Plasma Gelsolin (rhu-pGSN) Following Intravenous Administration to Healthy Volunteers

Abstract

Plasma gelsolin (pGSN) is a non-immunosuppressive anti-inflammatory immunomodulator with demonstrated efficacy in animal models of acute lung injury. Its therapeutic potential for moderate-to-severe acute respiratory distress syndrome is currently under investigation. This randomized, double-blind, placebo-controlled study assessed the safety, pharmacokinetics, and immunogenicity of multiple ascending doses of recombinant human pGSN (rhu-pGSN) in healthy volunteers. Thirty-two participants were enrolled across four dose cohorts (6, 12, 18, and 24 mg/kg of body weight), randomized 3:1 to receive five daily intravenous (IV) infusions of rhu-pGSN or placebo. Plasma pGSN concentrations increased as dose increased after single and multiple IV administrations. Following the final dose, geometric mean C_max ranged from 218.9 to 970.9 µg/mL, and geometric mean AUC_0–inf ranged from 6634.8 to 17,779.1 h µg/mL across four dose levels. Ten subjects (41.7%) who received rhu-pGSN reported a total of 13 adverse events (AEs), and one subject (12.5%) who received placebo reported an AE. All AEs were mild or moderate. No anti-rhu-pGSN antibodies were detected pre-dose or at Day 28 post first dose. Overall, five IV rhu-pGSN doses (up to 24 mg/kg daily) appeared safe and well tolerated.