title: Pharmacokinetics and safety profile of the human anti-Pseudomonas aeruginosa serotype O11 immunoglobulin M monoclonal antibody KBPA-101 in healthy volunteers.
abstract: KBPA-101 is a human monoclonal antibody of the immunoglobulin M isotype, which is directed against the O-polysaccharide moiety of Pseudomonas aeruginosa serotype O11. This double-blind, dose escalation study evaluated the safety and pharmacokinetics of KBPA-101 in 32 healthy volunteers aged 19 to 46 years. Each subject received a single intravenous infusion of KBPA-101 at a dose of 0.1, 0.4, 1.2, or 4 mg/kg of body weight or placebo infused over 2 h. Plasma samples for pharmacokinetic assessments were taken before infusion as well as 0.25, 0.5, 1, 2, 2.5, 4, 6, 8, 12, 24, 36, and 48 h and 4, 7, 10, and 14 days after start of dosing. Plasma concentrations of KBPA-101 were detected with mean maximum concentrations of drug in plasma of 1,877, 7,571, 24,923, and 83,197 ng/ml following doses of 0.1, 0.4, 1.2, and 4.0 mg/kg body weight, respectively. The mean elimination half-life was between 70 and 95 h. The mean volume of distribution was between 4.76 and 5.47 liters. Clearance ranged between 0.039 and 0.120 liters/h. At the highest dose of 4.0 mg/kg, plasma KBPA-101 levels were greater than 5,000 ng/ml for 14 days. KBPA-101 exhibited linear kinetics across all doses. No anti-KBPA-101 antibodies were detected after dosing in any subject. Overall, the human monoclonal antibody KBPA-101 was well tolerated over the entire dose range in healthy volunteers, and no serious adverse events have been reported.
authors.affiliation: Kenta Biotech, Rehhagstrasse 79, 3018 Bern, Switzerland. hedvika.lazar@kentabiotech.com
authors.forename: Hedvika
authors.initials: H
authors.lastname: Lazar
authors.forename: Michael P
authors.initials: MP
authors.lastname: Horn
authors.forename: Adrian W
authors.initials: AW
authors.lastname: Zuercher
authors.forename: Martin A
authors.initials: MA
authors.lastname: Imboden
authors.forename: Peter
authors.initials: P
authors.lastname: Durrer
authors.forename: Michael
authors.initials: M
authors.lastname: Seiberling
authors.forename: Rolf
authors.initials: R
authors.lastname: Pokorny
authors.forename: Christophe
authors.initials: C
authors.lastname: Hammer
authors.forename: Alois B
authors.initials: AB
authors.lastname: Lang
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M