Randomized, double-blind phase II study of anti-endotoxin antibody (E5) as adjuvant therapy in humans with serious gram-negative infections.
Xomen-E5 (E5) is a murine monoclonal IgM antibody (MAb) that binds to the lipid A epitope of endotoxin. The MAb was developed by immunization against the J5 mutant of Escherichia coli. Prior studies in humans have shown safety and T1/2 of 18.4 hours. In this double blind study patients suspected to have life threatening gram-negative infections were randomized to receive 2 doses, 24 hours apart, of placebo (P), 2.5 mg/kg E5, or 7.5 mg/kg E5. Overall 23 patients had a documented serious gram-negative infection and received at least one dose of study drug. Mortality 3 days after last infusion was 2 of 9 for P, 0 of 9 for 2.5 mg/kg, and 0 of 5 for 7.5 mg/kg. By 21 days after therapy one E5 treated patient had died. Wheezes occurred in one E5 treated patient. Eight of 15 E5 patients treated had IgG anti-murine antibodies by 3 weeks after therapy. These data suggest the need to pursue studies designed to verify that E5 reduced mortality and morbidity in seriously ill patients with gram-negative infections.
Department of Medicine, St. Louis University, MO 63104.
R N
RN
Greenberg
K M
KM
Wilson
A Y
AY
Kunz
N I
NI
Wedel
K J
KJ
Gorelick
D000911:Antibodies, Monoclonal / Q000627:therapeutic use / Q000633:toxicity*; D000917:Antibody Formation; D003131:Combined Modality Therapy; D004298:Dopamine / Q000627:therapeutic use; D004311:Double-Blind Method; D004341:Drug Evaluation; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008050:Lipid A / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D008050:Lipid A; D004298:Dopamine