OBJECTIVES:MEDI3902 is a bivalent, bispecific human immunoglobulin G1κ monoclonal antibody that binds to both the Pseudomonas aeruginosa PcrV protein involved in host cell cytotoxicity and the Psl exopolysaccharide involved in P. aeruginosa colonization and tissue adherence. MEDI3902 is being developed for the prevention of nosocomial P. aeruginosa pneumonia in high-risk patients. METHODS: This phase 1 dose-escalation study (NCT02255760) evaluated the safety, pharmacokinetics, antidrug antibody (ADA) responses and ex vivo anticytotoxicity and opsonophagocytic killing activities of MEDI3902 after a single intravenous infusion in healthy adults aged 18 to 60 years. Fifty-six subjects were randomized in a 3:1 ratio to receive 250, 750, 1500 or 3000 mg of MEDI3902 or placebo and followed for 60 days afterwards. RESULTS: Treatment-emergent adverse events (TEAEs) were mild or moderate in severity; no serious TEAEs were observed. The most common TEAEs were infusion-related reactions. MEDI3902 exhibited approximately linear pharmacokinetics across the 250, 750 and 1500 mg doses and nonlinear pharmacokinetics between the 1500 and 3000 mg doses. One subject in the 3000 mg group tested positive for ADA on day 61 and had a lower MEDI3902 serum concentration from days 43 to 61 than ADA-negative subjects. Serum anticytotoxicity antibody concentrations and opsonophagocytic killing activity were correlated with MEDI3902 serum concentrations across all doses. CONCLUSIONS: Phase 1 study results of MEDI3902 in healthy subjects support further evaluation of its safety and efficacy in subjects at risk for P. aeruginosa pneumonia.
RCT Entities:
OBJECTIVES:MEDI3902 is a bivalent, bispecific human immunoglobulin G1κ monoclonal antibody that binds to both the Pseudomonas aeruginosa PcrV protein involved in host cell cytotoxicity and the Psl exopolysaccharide involved in P. aeruginosa colonization and tissue adherence. MEDI3902 is being developed for the prevention of nosocomial P. aeruginosa pneumonia in high-risk patients. METHODS: This phase 1 dose-escalation study (NCT02255760) evaluated the safety, pharmacokinetics, antidrug antibody (ADA) responses and ex vivo anticytotoxicity and opsonophagocytic killing activities of MEDI3902 after a single intravenous infusion in healthy adults aged 18 to 60 years. Fifty-six subjects were randomized in a 3:1 ratio to receive 250, 750, 1500 or 3000 mg of MEDI3902 or placebo and followed for 60 days afterwards. RESULTS: Treatment-emergent adverse events (TEAEs) were mild or moderate in severity; no serious TEAEs were observed. The most common TEAEs were infusion-related reactions. MEDI3902 exhibited approximately linear pharmacokinetics across the 250, 750 and 1500 mg doses and nonlinear pharmacokinetics between the 1500 and 3000 mg doses. One subject in the 3000 mg group tested positive for ADA on day 61 and had a lower MEDI3902 serum concentration from days 43 to 61 than ADA-negative subjects. Serum anticytotoxicity antibody concentrations and opsonophagocytic killing activity were correlated with MEDI3902 serum concentrations across all doses. CONCLUSIONS: Phase 1 study results of MEDI3902 in healthy subjects support further evaluation of its safety and efficacy in subjects at risk for P. aeruginosa pneumonia.
Authors: David M P De Oliveira; Brian M Forde; Timothy J Kidd; Patrick N A Harris; Mark A Schembri; Scott A Beatson; David L Paterson; Mark J Walker Journal: Clin Microbiol Rev Date: 2020-05-13 Impact factor: 26.132
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