A Randomized Study of a Monoclonal Antibody (Pagibaximab) to Prevent Staphylococcal Sepsis

作者：Weisman Leonard E^*; Thackray Helen M; Steinhorn Robin H; Walsh William F; Lassiter Herbert A; Dhanireddy Ramasubbareddy; Brozanski Beverly S; Palmer Kristine G H; Trautman Michael S; Escobedo Marilyn; Meissner H Cody; Sasidharan Pontthenkandath; Fretz Jennifer; Kokai Kun John F; Kramer William G; Fischer Gerald W; Mond James J

来源：Pediatrics, 2011, 128(2): 271-279.

DOI：10.1542/peds.2010-3081

• safety
• pharmacokinetics
• monoclonal antibody
• chimeric
• immunoglobulin
• staphylococcus
• sepsis
• very low birth weight
• newborn
• immunogenic
• nosocomial infection

BACKGROUND: Pagibaximab, a human chimeric monoclonal antibody developed against lipoteichoic acid, was effective against staphylococci preclinically and seemed safe and well tolerated in phase 1 studies.
OBJECTIVE: To evaluate the clinical activity, pharmacokinetics, safety, and tolerability of weekly pagibaximab versus placebo infusions in very low birth weight neonates.
PATIENTS AND METHODS: A phase 2, randomized, double-blind, placebo-controlled study was conducted at 10 NICUs. Patients with a birth weight of 700 to 1300 g and 2 to 5 days old were randomly assigned to receive 3 once-a-week pagibaximab (90 or 60 mg/kg) or placebo infusions. Blood was collected for pharmacokinetics, bacterial killing, and safety analyses. Adverse event and clinical outcome data were collected.
RESULTS: Eighty-eight patients received pagibaximab at 90 (n = 22) or 60 (n = 20) mg/kg or placebo (n = 46). Groups were not different in demography, mortality, or morbidity. Pagibaximab demonstrated linear pharmacokinetics, a 14.5-day half-life, and nonimmunogenicity. Definite staphylococcal sepsis occurred in 0%, 20%, and 13% (P < .11) and nonstaphylococcal sepsis occurred in 0%, 10%, and 15% (P < .15) of patients in the 90 mg/kg, 60 mg/kg, and placebo groups, respectively. In all patients with staphylococcal sepsis, estimated or observed pagibaximab levels were <500 mu g/mL (target level) at infection.
CONCLUSIONS: Three once-a-week 90 or 60 mg/kg pagibaximab infusions, in high-risk neonates, seemed safe and well tolerated. No staphylococcal sepsis occurred in infants who received 90 mg/kg. Target levels were only consistently achieved after 2 to 3 doses. Dose optimization should enhance protection. Pediatrics 2011; 128: 271-279

• 出版日期2011-8
• 单位西北大学