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.
Harkonen
S
S
XOMA Corporation, Berkeley, California 94710.
Scannon
P
P
Mischak
R P
RP
Spitler
L E
LE
Foxall
C
C
Kennedy
D
D
Greenberg
R
R
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D004341:Drug Evaluation; D005260:Female; D006090:Gram-Negative Bacteria; D006207:Half-Life; D006801:Humans; D008050:Lipid A / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000628:therapy*
D000911:Antibodies, Monoclonal; D008050:Lipid A