Ascending Single Dose Study of Rhu-pGelsolin in Patients With Decreased Gelsolin Levels

Summary

This study is designed to assess the pharmacokinetics and safety of an infusion of a single dose of recombinant plasma gelsolin (rhu-pGelsolin) when given to patients admitted to the Intensive Care Unit with documented low levels of natural gelsolin. It is believed that this drug will raise the gelsolin levels in these patients and decrease the probability that they will develop complications from their underlying disease such as organ system failure or death.

Timeline

Start

2008-03

Primary completion

2010-03

Completion

2010-05

Publications

• Background Lee PS, Waxman AB, Cotich KL, Chung SW, Perrella MA, Stossel TP. Plasma gelsolin is a marker and therapeutic agent in animal sepsis. Crit Care Med. 2007 Mar;35(3):849-55. doi: 10.1097/01.CCM.0000253815.26311.24.
• Background Lee PS, Drager LR, Stossel TP, Moore FD, Rogers SO. Relationship of plasma gelsolin levels to outcomes in critically ill surgical patients. Ann Surg. 2006 Mar;243(3):399-403. doi: 10.1097/01.sla.0000201798.77133.55.
• Background Christofidou-Solomidou M, Scherpereel A, Solomides CC, Christie JD, Stossel TP, Goelz S, DiNubile MJ. Recombinant plasma gelsolin diminishes the acute inflammatory response to hyperoxia in mice. J Investig Med. 2002 Jan;50(1):54-60. doi: 10.2310/6650.2002.33518.
• Background Rothenbach PA, Dahl B, Schwartz JJ, O'Keefe GE, Yamamoto M, Lee WM, Horton JW, Yin HL, Turnage RH. Recombinant plasma gelsolin infusion attenuates burn-induced pulmonary microvascular dysfunction. J Appl Physiol (1985). 2004 Jan;96(1):25-31. doi: 10.1152/japplphysiol.01074.2002. Epub 2003 May 2.
• Background Mounzer KC, Moncure M, Smith YR, Dinubile MJ. Relationship of admission plasma gelsolin levels to clinical outcomes in patients after major trauma. Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1673-81. doi: 10.1164/ajrccm.160.5.9807137.
• Background DiNubile MJ, Stossel TP, Ljunghusen OC, Ferrara JL, Antin JH. Prognostic implications of declining plasma gelsolin levels after allogeneic stem cell transplantation. Blood. 2002 Dec 15;100(13):4367-71. doi: 10.1182/blood-2002-06-1672. Epub 2002 Aug 1.
• Background Suhler E, Lin W, Yin HL, Lee WM. Decreased plasma gelsolin concentrations in acute liver failure, myocardial infarction, septic shock, and myonecrosis. Crit Care Med. 1997 Apr;25(4):594-8. doi: 10.1097/00003246-199704000-00007.

Drugs

Indications