Leonard E. Weisman, Helen M. Thackray, Joseph A. Gracia-Prats, Mirjana Nesin, Jimmy Mond, Joseph H. Schneider, Karen E. Johnson, Karen Adams, William G. Kramer, Gerald W. Fischer. Section of Neonatology Baylor College of Medicine, Houston, TX; Division of Neonatology, Weill Medical College, New York, NY; Biosynexus Incorporated, Gaithersburg, MD.

BACKGROUND: Coagulase-negative staphylococcal (CoNS) sepsis is a major cause of morbidity in very low birth weight infants. A human chimeric monoclonal antibody (BSYX-A110) was developed against staphylococcal lipoteichoic acid. When tested in adults, the antibody appeared safe and serum anti-LTA and bacterial killing levels were dose related and highly correlated.

OBJECTIVE: This study evaluates the safety, tolerability, and pharmacokinetics of BSYX-A110 in very low birth weight neonates.

DESIGN/METHODS: A Phase I/II randomized, double blind, placebo controlled dose escalation study enrolled very low birth weight infants (700-1300g), 3-7 days old, to receive 2 doses 14 days apart of either BSYX-A110 at 10, 30, 60, or 90 mg/kg or placebo at a 2:1 ratio. Blood and urine were obtained pre- and post-infusion for analysis of safety and pharmacokinetics. Data was gathered on adverse events and cultures of staphylococcal organisms causing sepsis during the study were collected.

RESULTS: 53 subjects received at least one dose of study drug. The average gestational age was 27.58 weeks; average birth weight was 1003g. All SAEs were deemed unrelated or probably not related to drug. Common morbidities and mortality were not different across study groups. No evidence of immunogenicity of BYSX-A110 was detected. A noncompartmental model demonstrated linear pharmacokinetics of BSYX-A110. Mean clearance, volume of distribution, and elimination half-life were independent of dose. Terminal elimination half life was 20.5 ±6.8 days. All CoNS causing sepsis during the study were opsonizable by BSYX-A110.

CONCLUSION: Two infusions of BSYX-A110, administered two weeks apart to high-risk neonates appeared safe and tolerable, and linear pharmacokinetics were observed. Evaluation of more frequent doses, at the highest dose levels tested, in neonates at high-risk of CoNS sepsis is warranted.