Phase I study of a murine monoclonal anti-lipid A antibody in bacteremic and nonbacteremic patients.

Nine patients with suspected gram-negative bacterial sepsis were studied to determine the safety, pharmacokinetics, and immunogenicity of XMMEN-0E5, a murine immunoglobulin M monoclonal antibody directed against the core lipid A region of bacterial endotoxin. Antibody was administered by single intravenous infusion of 1 to 4 h duration at doses ranging from 0.1 to 15 mg/kg. Five patients had positive blood cultures for gram-negative bacteria, one patient had Torulopsis septicemia, one patient had gram-negative bacterial meningitis, and two patients were culture negative. No evidence of antibody-mediated toxicity was observed at any dose level. The serum half-life of the antibody was approximately 10 h at doses of 0.1 to 7.5 mg/kg and approximately 18 h at a dose of 15 mg/kg. No apparent difference in clearance of antibody was observed between bacteremic and nonbacteremic patients. Human anti-mouse antibodies were detected in the sera of three evaluable patients that received doses equal to or greater than 2.0 mg/kg but not in patients that received lower doses of antibody. This study demonstrates that XMMEN-0E5 is well tolerated at doses from 0.1 to 15 mg/kg and may be immunogenic at doses of 2.0 mg/kg and above. Controlled trials to establish the efficacy of this antibody in the treatment of gram-negative bacteremia are indicated.