Z. Magyarics, Fraser Leslie, Johann Bartko
2019
Citations
1
Influential Citations
16
Citations
Quality indicators
Journal
Antimicrobial agents and chemotherapy
Abstract
ASN100 is a novel antibody combination of two fully human IgG1 kappa monoclonal antibodies, ASN-1 and ASN-2 which neutralize six Staphylococcus aureus cytotoxins, alpha-hemolysin (Hla) and five bi-component leukocidins. We assessed the safety, tolerability, and serum and lung pharmacokinetics of ASN100 in a randomized, double-blind, placebo-controlled single dose escalation first-in-human study.Fifty-two healthy volunteers were enrolled and randomized to receive either ASN-1, ASN-2, or a combination of both mAbs (ASN100), or corresponding placebo. Thirty-two subjects in the double-blind dose escalation portion of the study received ASN-1 or ASN-2 at a 200, 600, 1800, or 4000 mg dose, or placebo. Eight subjects received both mAbs simultaneously in a 1:1 ratio (ASN100) at 3600 or 8000 mg, or placebos. Twelve additional subjects received open-label ASN100 at 3600 or 8000 mg to assess the pharmacokinetics of ASN-1 and ASN-2 in epithelial lining fluid (ELF) by bronchoalveolar lavage fluid sampling. Subjects were followed for 98 days (double-blind cohorts) or 30 days (open-label cohorts) for safety assessment.No dose-limiting toxicities were observed and all adverse events were mild and transient, with only two adverse events considered possibly related to the Investigational Product. ASN100 exhibited linear serum PK with a half-life of approximately three weeks and showed detectable penetration into the ELF. No treatment-emergent anti-drug antibody responses were detected. The toxin neutralizing potency of ASN100 in human serum was confirmed up to 58 days post-dosing.The favorable safety profile, ELF penetration, and maintained functional activity in serum supported the further clinical development of ASN100.