Ascending Single Dose Study of Rhu-pGelsolin in Patients With Decreased Gelsolin Levels
September 27, 2010 updated by: Critical Biologics Corporation
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Anticipated)
40
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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SAR
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Hong Kong, SAR, Hong Kong
- Queen Mary Hospital; University of Hong Kong
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Placebo Comparator: Placebo
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Vehicle control given as IV infusion over 1 hour
Other Names:
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Experimental: Low dose
3 mg/kg of rhu-pGelsolin given as an IV infusion over 1 hour
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IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour
Other Names:
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Experimental: Mid-dose
6 mg/kg of rhu-pGelsolin given as an IV infusion over 1 hour
|
IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour
Other Names:
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Experimental: High dose
6 mg/kg of rhu-pGelsolin given a an IV infusion over 1 hour once a day for 3 days
|
IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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Pharmacokinetics of plasma gelsolin
Time Frame: 72 hours
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72 hours
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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Adverse events and the development of anti-rhu-pGelsolin antibodies
Time Frame: 3 months
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3 months
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Pharmacodynamics of sepsis biomarkers
Time Frame: 72 hours
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72 hours
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Clinical outcomes (mortality, duration of ICU stay, duration of ventilator support, duration of hospital stay)
Time Frame: 28 days
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28 days
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Wai M Chan, MBBS, Queen Mary Hospital, Hong Kong
- Study Director: Selene Tam, PhD, University of Hong Kong; Clinical Trials Centre
- Study Chair: Richard C Straube, MD, Critical Biologics Corporation
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General 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. doi: 10.1097/01.CCM.0000253815.26311.24.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2008
Primary Completion (Actual)
March 1, 2010
Study Completion (Actual)
May 1, 2010
Study Registration Dates
First Submitted
April 30, 2008
First Submitted That Met QC Criteria
April 30, 2008
First Posted (Estimate)
May 5, 2008
Study Record Updates
Last Update Posted (Estimate)
September 29, 2010
Last Update Submitted That Met QC Criteria
September 27, 2010
Last Verified
April 1, 2010
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CBC101
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