Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab')2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels. To evaluate whether administration of afelimomab, an anti-tumor necrosis factor F(ab')2 monoclonal antibody fragment, would reduce 28-day all-cause mortality in patients with severe sepsis and elevated serum levels of IL-6 designed to identify patients with serum interleukin-6 levels above (test positive) or below (test negative) approximately 1000 pg/mL. Of the 2,634 patients, 998 were stratified into the test-positive group, 1,636 into the test-negative group. They were then randomly assigned 1:1 to receive afelimomab 1 mg/kg or placebo for 3 days and were followed for 28 days. The a priori population for efficacy
Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis: The RAMSES Study. This study investigated whether treatment with the anti-tumor necrosis factor-alpha monoclonal antibody afelimomab would improve survival in septic patients with serum interleukin (IL)-6 concentrations of >1000 pg/mL either afelimomab (n = 224) or placebo (n = 222). Patients with a negative IL-6 test (n = 498) were not randomized and were followed up for 28 days. Treatment consisted of 15-min infusions of 1 mg/kg afelimomab or matching placebo every 8 hrs for 3 days. Standard surgical and intensive care therapy was otherwise delivered. The study was terminated prematurely after an interim analysis estimated
factor monoclonal antibody F(ab')2 fragment (afelimomab). University hospital intensive care unit. A total of 23 nontrauma patients with severe sepsis or septic shock and ten multiple trauma patients. Septic patients were randomized for additional experimental treatment when initial interleukin (IL)-6 serum level was above 1000 pg/mL. Randomized patients received 1.0 mg/kg afelimomab or placebo three treated with afelimomab. In patients with severe sepsis, big-ET plasma levels are markedly increased, even above those of multiple trauma patients, in close relationship to IL-6 and IL-8, and with significant correlation to renal function and pulmonary vascular tone.
A multicenter, open-label, prospective, randomized, dose-ranging pharmacokinetic study of the anti-TNF-alpha antibody afelimomab in patients with sepsis syndrome. To investigate the pharmacokinetics and safety of afelimomab, a murine antibody fragment against human tumor necrosis factor (TNF)-alpha in patients with sepsis. Multicenter, randomized, open-label, placebo-controlled phase I/II clinical trial. Intensive care units of six academic medical centers in the United States. Forty-eight patients with a clinical diagnosis of sepsis who received standard supportive care and antimicrobial therapy. Patients received 0.3, 1.0, or 3.0 mg/kg afelimomab or placebo intravenously over 20 min. Three patients in each dose group received single doses; the remaining nine patients in each group
(MAK195F, BAYx1351 or afelimomab), activated protein C, platelet activating factor receptor antagonist, anti-Enterobacteriaceae common antigen antibody, and the granulocyte colony stimulating factor filgrastim
-tumor necrosis factor antibody F(ab')2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels. Crit Care Med. 2004 Nov;32(11):2173-82. Küster H, Weiss M, Willeitner AE, Detlefsen S, Jeremias I, Zbojan J, Geiger R, Lipowsky G, Simbruner G. Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. Lancet
S, Kaul M, Teoh L, Van Meter L, Daum L, Lemeshow S, Hicklin G, Doig C; Monoclonal Anti-TNF: a Randomized Controlled Sepsis Study Investigators. Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab')2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels. Crit Care Med. 2004 Nov;32(11):2173-82. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel