Methods: The safety, tolerability, and serum and lung PK of single intravenous infusion of ASN100 was evaluated in a Phase 1 study. Eight subjects (3:1 randomization) in two double-blind cohorts received ASN100 (doses of 3600 mg or 8000 mg) or placebo. ASN-1 and ASN-2 were administered in a fixed dose 1:1 ratio. Twelve subjects received ASN100 open-label at doses of 3600 mg or 8000 mg and each underwent two bronchoalveolar lavage (BAL) fluid collections either on days 1 and 30 or on days 2 and 8 post-dosing. ASN‑1 and ASN-2 concentrations were determined by ELISA. The ELF concentrations were normalized based on urea concentrations in serum and BAL fluid.
Results: No dose limiting toxicity was observed. Adverse events (AEs) showed no association of increased incidence with higher dose. All AEs were mild or moderate in severity, with 83.3% of subjects receiving ASN100 reporting at least one AE versus 100% of placebo subjects. A dose proportional increase in serum peak and exposure (AUC) of ASN-1 and ASN-2 was observed and the serum PK of ASN-1 and ASN-2 were comparable (approximate half-life of each antibody was 3 weeks). Penetration of ASN-1 and ASN-2 into the ELF of the lung was observed at the first post-dose time point of 24 hours, peak concentrations were observed after day 2 and the mAbs remained detectable at day 30.
Conclusion: ASN100 was safe and well tolerated at doses up to 8000 mg (4000 mg ASN‑1 and 4000 mg ASN-2). The PK profiles of ASN-1 and ASN-2 were comparable following simultaneous administration. Significant lung concentrations of each mAb were demonstrated between day 1 and 30 post-dosing. These data support continued clinical development of ASN100 for the prevention and treatment of S. aureus pneumonia.
Arsanis Biosciences GmbH:
Arsanis, Inc.: Shareholder , Share options
S. A. Luperchio, Arsanis Inc: Employee and Shareholder , Salary
J. Bartko, None
C. Schörgenhofer, None
M. Schwameis, None
U. Derhaschnig, None
H. Lagler, None
L. Stiebellehner, None
B. Jilma, Arsanis Biosciences GmbH: Investigator , Investigator fee
C. Stevens, Arsanis Inc.: Employee and Shareholder , Salary
E. Nagy, Arsanis: Employee and Shareholder , Salary