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

Primary Purpose

Low Gelsolin, Trauma, Infection

Status

Completed

Phase

Phase 1

Locations

Hong Kong

Study Type

Interventional

Intervention

rhu-pGelsolin

Placebo

About this trial

This is an interventional treatment trial for Low Gelsolin focused on measuring Gelsolin, Trauma, Pneumonia, Peritonitis, Burn, Infection, Sepsis, Systemic Inflammatory Response Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Queen Mary Hospital; University of Hong Kong

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Low dose

Mid-dose

High dose

Arm Description

Placebo

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

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

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

Outcomes

Primary Outcome Measures

Pharmacokinetics of plasma gelsolin

Secondary Outcome Measures

Adverse events and the development of anti-rhu-pGelsolin antibodies

Pharmacodynamics of sepsis biomarkers

Clinical outcomes (mortality, duration of ICU stay, duration of ventilator support, duration of hospital stay)

Full Information

NCT ID

NCT00671307

First Posted

April 30, 2008

Last Updated

September 27, 2010

Sponsor

Critical Biologics Corporation

1. Study Identification

Unique Protocol Identification Number

NCT00671307

Brief Title

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

2. Study Status

Record Verification Date

April 2010

Overall Recruitment Status

Completed

Study Start Date

March 2008 (undefined)

Primary Completion Date

March 2010 (Actual)

Study Completion Date

May 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Critical Biologics Corporation

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Low Gelsolin, Trauma, Infection, Burns

Keywords

Gelsolin, Trauma, Pneumonia, Peritonitis, Burn, Infection, Sepsis, Systemic Inflammatory Response Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Arm Title

Low dose

Arm Type

Experimental

Arm Description

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

Arm Title

Mid-dose

Arm Type

Experimental

Arm Description

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

Arm Title

High dose

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

rhu-pGelsolin

Other Intervention Name(s)

Recombinant plasma gelsolin, CBC-100, Solinex

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Vehicle control

Intervention Description

Vehicle control given as IV infusion over 1 hour

Primary Outcome Measure Information:

Title

Pharmacokinetics of plasma gelsolin

Time Frame

72 hours

Secondary Outcome Measure Information:

Title

Adverse events and the development of anti-rhu-pGelsolin antibodies

Time Frame

3 months

Title

Pharmacodynamics of sepsis biomarkers

Time Frame

72 hours

Title

Clinical outcomes (mortality, duration of ICU stay, duration of ventilator support, duration of hospital stay)

Time Frame

28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wai M Chan, MBBS

Organizational Affiliation

Queen Mary Hospital, Hong Kong

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Selene Tam, PhD

Organizational Affiliation

University of Hong Kong; Clinical Trials Centre

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Richard C Straube, MD

Organizational Affiliation

Critical Biologics Corporation

Official's Role

Study Chair

Facility Information:

Facility Name

Queen Mary Hospital; University of Hong Kong

City

Hong Kong

State/Province

SAR

Country

Hong Kong

12. IPD Sharing Statement

Citations:

PubMed Identifier

17205019

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.

Results Reference

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PubMed Identifier

16495706

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.

Results Reference

background

PubMed Identifier

11813829

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.

Results Reference

background

PubMed Identifier

12730154

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.

Results Reference

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PubMed Identifier

10556139

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.

Results Reference

background

PubMed Identifier

12393536

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.

Results Reference

background

PubMed Identifier

9142022

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.

Results Reference

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

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