Clinical trial NCT00671307: Ascending Single Dose Study of Rhu-pGelsolin in Patients With Decreased Gelsolin Levels
Official title: Phase 1b Randomized, Double-blind, Placebo-controlled, Ascending Single Dose Infusion Trial of the Pharmacokinetics of Rhu-pGelsolin in Patients With Decreased Natural Gelsolin Levels
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Low Gelsolin
Trauma
Infection
Burns
Keywords: Gelsolin
Trauma
Pneumonia
Peritonitis
Burn
Infection
Sepsis
Systemic Inflammatory Response Syndrome
Lead sponsor: Critical Biologics Corporation
Sponsor class: INDUSTRY
First posted: 2008-05-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: This is a randomized, double-blind, placebo-controlled, ascending single dose of rhu-pGelsolin infusion study. Thirteen subjects (10 active and 3 placebo) will be dosed at 3 mg/kg and 5 subjects (3 active and 2 placebo) will be dosed at 6 mg/kg. In addition, twenty-two subjects (18 active and 4 placebo) will be dosed at 6 mg/kg per day for 3 days. The Data Safety Monitoring Committee (DSMC) and Steering Committee will review the preceding dose safety data, and agree the tolerability prior to the enrolment for next higher dose. Blood samples will be collected during 1 hour infusion through 72 hours post dose for PK assessment after each dose.

Eligibility criteria: Inclusion Criteria:

* \>18 years of age
* Documented gelsolin level \<100 mg/mL
* Admission to ICU
* Women of child-bearing age have a negative pregnancy test
* Multiple Organ Failure score \< 4
* Catheter present through which blood samples can be taken
* Written Informed Consent obtained

Exclusion Criteria:

* Participation in other investigational treatment protocols
* Patients \<18 years of age
* Patients who have a modified Multiple Organ Failure score of \>=4
* Patient, who in the opinion of the Principal Investigator, are unlikely to be in the ICU for \>48 hours

Primary outcomes:
measure: Pharmacokinetics of plasma gelsolin
timeFrame: 72 hours
Secondary outcomes:
measure: Adverse events and the development of anti-rhu-pGelsolin antibodies
timeFrame: 3 months
measure: Pharmacodynamics of sepsis biomarkers
timeFrame: 72 hours
measure: Clinical outcomes (mortality, duration of ICU stay, duration of ventilator support, duration of hospital stay)
timeFrame: 28 days
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital; University of Hong Kong
state: SAR
Study officials:
affiliation: Queen Mary Hospital, Hong Kong
name: Wai M Chan, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Hong Kong; Clinical Trials Centre
name: Selene Tam, PhD
role: STUDY_DIRECTOR
affiliation: Critical Biologics Corporation
name: Richard C Straube, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.