Pilot clinical trial of an anti-TNFα monoclonal antibody for the treatment of septic shock

Abstract

To determine the safety and pharmacokinetics of an anti-tumour necrosis factor (TNF alpha) monoclonal antibody in the treatment of septic shock, and to evaluate the biological evolution of cytokine response. Open-label, prospective, pilot trial with escalating doses of a murine monoclonal antibody (B-C7) directed against TNF alpha. University medical centre intensive care unit. Nine patients with septic shock, who received standard supportive care and antimicrobial therapy in addition to the anti-TNF alpha antibody. Patients were treated intravenously with one of three escalating doses of B-C7 monoclonal antibody (MoAb): 0.4 mg/kg, 0.8 mg/kg, 1 mg/kg. MoAb was well tolerated despite the development of human anti-mouse antibodies (HAMA) for each patient; B-C7 plasma levels were dose-dependent. At study entry, TNF alpha and IL-6 levels were detected in six and seven patients respectively; IL-1 levels were low and interferon-gamma was undetectable. No side effects were noted during treatment regardless of the dose used; however, further studies are needed to determine the clinical efficacy of this agent in septic shock.