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

NCT ID: NCT00671307

Last Updated: 2010-09-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-03-31

Study Completion Date

2010-05-31

Brief Summary

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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

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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.

Conditions

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Low Gelsolin Trauma Infection Burns

Keywords

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Gelsolin Trauma Pneumonia Peritonitis Burn Infection Sepsis Systemic Inflammatory Response Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Vehicle control given as IV infusion over 1 hour

Low dose

3 mg/kg of rhu-pGelsolin given as an IV infusion over 1 hour

Group Type EXPERIMENTAL

rhu-pGelsolin

Intervention Type DRUG

IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour

Mid-dose

6 mg/kg of rhu-pGelsolin given as an IV infusion over 1 hour

Group Type EXPERIMENTAL

rhu-pGelsolin

Intervention Type DRUG

IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour

High dose

6 mg/kg of rhu-pGelsolin given a an IV infusion over 1 hour once a day for 3 days

Group Type EXPERIMENTAL

rhu-pGelsolin

Intervention Type DRUG

IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour

Interventions

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rhu-pGelsolin

IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour

Intervention Type DRUG

Placebo

Vehicle control given as IV infusion over 1 hour

Intervention Type DRUG

Other Intervention Names

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Recombinant plasma gelsolin CBC-100 Solinex Vehicle control

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Critical Biologics Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Critical Biologics Corporation

Principal Investigators

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Wai M Chan, MBBS

Role: PRINCIPAL_INVESTIGATOR

Queen Mary Hospital, Hong Kong

Selene Tam, PhD

Role: STUDY_DIRECTOR

University of Hong Kong; Clinical Trials Centre

Richard C Straube, MD

Role: STUDY_CHAIR

Critical Biologics Corporation

Locations

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Queen Mary Hospital; University of Hong Kong

Hong Kong, SAR, Hong Kong

Site Status

Countries

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Hong Kong

References

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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.

Reference Type BACKGROUND
PMID: 17205019 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16495706 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11813829 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12730154 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10556139 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12393536 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9142022 (View on PubMed)

Other Identifiers

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CBC101

Identifier Type: -

Identifier Source: org_study_id