H. Thackray, H. Lassiter, W. Walsh, B. Brozanski, R. Steinhorn, R. Dhanireddy, G. Fischer, L. E. Weisman, the MAB N003 Study Group. Biosynexus Incorporated, Gaithersburg, MD; University of Louisville, KY; Vanderbilt University, TN; University of Pittsburgh, PA; Northwestern University, IL; LSUHSC-Shreveport, LA; Baylor College of Medicine, TX.

BACKGROUND: Pagibaximab (PMAB), a human chimeric monoclonal, was developed against staphylococcal lipoteichoic acid for the prevention of staphylococcal infection. PMAB appeared safe with linear PK in early human studies.

OBJECTIVE: This study evaluates the safety, tolerability, PK, and clinical activity of PMAB in VLBW neonates.

DESIGN/METHODS: In this phase II study, 2-5 day old 700-1300g neonates were randomized to receive 3 doses 7 days apart of either PMAB or placebo. Blood and urine were obtained for analysis of safety and PK. Adverse event and outcome data were collected.

RESULTS: 88 subjects, with a mean birth weight of 992g and mean gestation of 28 weeks received at least one dose of study drug at 60 mg/kg (n=20), 90 mg/kg (n=22), or placebo (n=46). There were no significant demographic, mortality, or morbidity differences between study groups. All serious adverse events appeared unrelated or probably not related to PMAB. PMAB was non-immunogenic and demonstrated linear PK. Mean sustained PMAB levels over 500 µg/mL were seen for 3 weeks after the second infusion of 90 mg/kg. There was a trend for those treated with this dose to have fewer positive blood cultures due to any organism than other groups (18% vs. 40% and 30% in the 60 mg/kg and placebo groups, respectively; p <0.3). No subject in the 90 mg/kg group had confirmed staphylococcal sepsis compared to 20% and 13% in the 60 mg/kg and placebo groups, respectively (p<0.11). Estimated or observed PMAB levels were below 500 µg/mL at the time of staphylococcal sepsis in all cases except one.

CONCLUSIONS: Three infusions of Pagibaximab at 60 or 90 mg/kg, administered 1 week apart to high-risk neonates, appeared safe, well tolerated, with linear PK, and at 90 mg/kg produced mean levels of antibody over 500 µg/mL, which may be potentially protective for staphylococcal sepsis. Additional larger studies in high-risk neonates are warranted to further evaluate the current findings.

Co-sponsors: Biosynexus and GSK Biologics