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

Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00671307
• Other study ID #: CBC101
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 30, 2008
• Last updated: September 27, 2010
• Start date: March 2008
• Est. completion date: May 2010

Study information

• Verified date: April 2010
• Source: Critical Biologics Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hong Kong: Department of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Burns
• Infection
• Low Gelsolin
• Trauma

Intervention

Drug:
• rhu-pGelsolin
IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour
• Placebo
Vehicle control given as IV infusion over 1 hour

Locations

Country	Name	City	State
Hong Kong	Queen Mary Hospital; University of Hong Kong	Hong Kong	SAR

Sponsors (1)

Lead Sponsor	Collaborator
Critical Biologics Corporation

Country where clinical trial is conducted

Hong Kong, 

References & Publications (7)

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. — View 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. Epub 2002 Aug 1. — View 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. — View 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. — View 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. — View 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. Epub 2003 May 2. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics of plasma gelsolin		72 hours	No
Secondary	Adverse events and the development of anti-rhu-pGelsolin antibodies		3 months	Yes
Secondary	Pharmacodynamics of sepsis biomarkers		72 hours	No
Secondary	Clinical outcomes (mortality, duration of ICU stay, duration of ventilator support, duration of hospital stay)		28 days	Yes