A Randomized Study of a Monoclonal Antibody (Pagibaximab) to Prevent Staphylococcal Sepsis
Weisman LE et al. – 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.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.
- 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% and nonstaphylococcal sepsis occurred in 0%, 10%, and 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 ug/mL (target level) at infection.