Leonard E. Weisman, Gerald W. Fischer, George T. Mandy, Helen Thackray, Karen E. Johnson, Beth E. Krayer, Karen M. Adams, Richard F. Schuman and James J. Mond, Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, TX; and, Biosynexus, Gaithersburg, MD.

Background: A humanized mouse chimeric monoclonal antibody (BSYX-A110), directed against lipoteichoic acid (LTA) and protective in animal models for coagulase negative staphylococci and S.aurcus, has been developed for prevention of CONS infection in high-risk patients.

Objective: Evaluate the safety and pharmacokinetics of BSYX-A110 in healthy human adults.

Design/Methods: This was an open label dose-ranging study of one dose of 3 or 10 mg/kg of a 10 mg/ml product. Primary endpoints were safety and tolerability. Secondary endpoints were anti-LTA levels and opsonic activity. A history, physical exam and vital signs, blood studies (CBC, liver and renal function, chemistries, pharmacokinetics studies) and urinalysis were obtained prior to infusion, and at 3,7,14,&28 days post-infusion. During and immediately after infusion volunteers were closely monitored. Volunteers collected observations in a diary for 14 days post-infusion. HAMA/HACA levels were obtained prior to infusion and 28 days later. Anti-LTA activity was measured by ELISA. Opsonic activity was determined with a standard bacterial killing assay.

Results: Each dose group had: 4 healthy volunteers (24 to 50 years old); 3 whites and 1 black, 3 females and 1 male. Infusion volumes were 18.22cc to 93cc. No infusion, drug, or dose related adverse events were observed. There was no significant change from baseline in vital signs, blood or urine studies, or HAMA/HACA levels. Anti-LTA levels were dose-related, peaked at 264±54 ug/ml immediately and at 101±39 ug/ml at 28 days. This IgG1 monocolonal antibody demonstrated a half-life (beta) of 30±10.4 days. Bacterial killing levels were dose-related, peaked at 96±2% immediately and at 69±19% at 28 days. Anti-LTA and bacterial killing levels were highly correlated (R=0.67).

Conclusions: BSYX-A110 at 3 and 10 mg/kg appears: 1) safe and tolerable in adults, 2) to produce dose related levels of anti-LTA and bacterial killing in serum that are highly correlated, 3) to have a half-life similar to other IgG1 antibodies, 4) to approach levels of antibody that are protective in animal studies. Safety and pharmacokinetic studies of BSYX-A110 in a target population of high-risk infants is indicated.

Disclosure: Funded by Biosynexus Incorporated