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

Sponsor:	Critical Biologics Corporation
Information provided by:	Critical Biologics Corporation
ClinicalTrials.gov Identifier:	NCT00671307

Purpose

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.

Condition	Intervention	Phase
Low Gelsolin Trauma Infection Burns	Drug: rhu-pGelsolin Drug: Placebo	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Pharmacokinetics/Dynamics Study
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

Resource links provided by NLM:

MedlinePlus related topics: Burns Injuries Sepsis Wounds

U.S. FDA Resources

Further study details as provided by Critical Biologics Corporation:

Primary Outcome Measures:

Pharmacokinetics of plasma gelsolin [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Adverse events and the development of anti-rhu-pGelsolin antibodies [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Pharmacodynamics of sepsis biomarkers [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
Clinical outcomes (mortality, duration of ICU stay, duration of ventilator support, duration of hospital stay) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	March 2008
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo: Placebo Comparator Placebo	Drug: Placebo Vehicle control given as IV infusion over 1 hour
Low dose: Experimental 3 mg/kg of rhu-pGelsolin given as an IV infusion over 1 hour	Drug: rhu-pGelsolin IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour
Mid-dose: Experimental 6 mg/kg of rhu-pGelsolin given as an IV infusion over 1 hour	Drug: rhu-pGelsolin IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour
High dose: Experimental 6 mg/kg of rhu-pGelsolin given a an IV infusion over 1 hour once a day for 3 days	Drug: rhu-pGelsolin IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00671307

Locations

Hong Kong, SAR
Queen Mary Hospital; University of Hong Kong
Hong Kong, SAR, Hong Kong

Sponsors and Collaborators

Critical Biologics Corporation

Investigators

Principal Investigator:	Wai M Chan, MBBS	Queen Mary Hospital;
Study Director:	Selene Tam, PhD	University of Hong Kong; Clinical Trials Centre
Study Chair:	Richard C Straube, MD	Critical Biologics Corporation

More Information

Publications:

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.

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.

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.

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. 2004 Jan;96(1):25-31. Epub 2003 May 2.

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.

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. Epub 2002 Aug 1.

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.

Responsible Party:	Critical Biologics Corporation ( Richard Straube, MD/ Chief Medical Officer )
Study ID Numbers:	CBC101
Study First Received:	April 30, 2008
Last Updated:	March 23, 2009
ClinicalTrials.gov Identifier:	NCT00671307 History of Changes
Health Authority:	Hong Kong: Department of Health

Keywords provided by Critical Biologics Corporation:

Gelsolin
Trauma
Pneumonia
Peritonitis

Burn
Infection
Sepsis
Systemic Inflammatory Response Syndrome

Additional relevant MeSH terms:

Communicable Diseases
Infection

ClinicalTrials.gov processed this record on February 08, 2010