1. Academic Validation
  2. A randomized study of a monoclonal antibody (pagibaximab) to prevent staphylococcal sepsis

A randomized study of a monoclonal antibody (pagibaximab) to prevent staphylococcal sepsis

  • Pediatrics. 2011 Aug;128(2):271-9. doi: 10.1542/peds.2010-3081.
Leonard E Weisman 1 Helen M Thackray Robin H Steinhorn William F Walsh Herbert A Lassiter Ramasubbareddy Dhanireddy Beverly S Brozanski Kristine G H Palmer Michael S Trautman Marilyn Escobedo H Cody Meissner Pontthenkandath Sasidharan Jennifer Fretz John F Kokai-Kun William G Kramer Gerald W Fischer James J Mond
Affiliations

Affiliation

  • 1 Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030-2303, USA. lweisman@bcm.edu
Abstract

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 μg/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.

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