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

NCT00671307 | Completed Phase 1 DMC

• 1 other identifier: CBC101
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Low Gelsolin; Trauma; Infection; Burns

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics of plasma gelsolin

  72 hours

Secondary Outcomes (3)

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

  3 months

• Pharmacodynamics of sepsis biomarkers

  72 hours

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

  28 days

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Low dose

EXPERIMENTAL

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

Drug: rhu-pGelsolin

Mid-dose

EXPERIMENTAL

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

Drug: rhu-pGelsolin

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

Interventions

rhu-pGelsolin DRUG

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

Also known as: Recombinant plasma gelsolin, CBC-100, Solinex

High dose; Low dose; Mid-dose

Placebo DRUG

Vehicle control given as IV infusion over 1 hour

Also known as: Vehicle control

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>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

You may not qualify if:

• 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

Sponsors & Collaborators

• Critical Biologics Corporation: lead

Study Sites (1)

Queen Mary Hospital; University of Hong Kong

Hong Kong, SAR, Hong Kong

Location

Related Publications (7)

• 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.

  PMID: 17205019 BACKGROUND

• 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.

  PMID: 16495706 BACKGROUND

• 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.

  PMID: 11813829 BACKGROUND

• 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.

  PMID: 12730154 BACKGROUND

• 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.

  PMID: 10556139 BACKGROUND

• 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.

  PMID: 12393536 BACKGROUND

• 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.

  PMID: 9142022 BACKGROUND

MeSH Terms

Conditions

Wounds and Injuries; Infections; Burns; Meretoja syndrome; Pneumonia; Peritonitis; Sepsis; Systemic Inflammatory Response Syndrome

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Intraabdominal Infections; Peritoneal Diseases; Digestive System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Wai M Chan, MBBS

  Queen Mary Hospital, Hong Kong

  PRINCIPAL INVESTIGATOR

• Selene Tam, PhD

  University of Hong Kong; Clinical Trials Centre

  STUDY DIRECTOR

• Richard C Straube, MD

  Critical Biologics Corporation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 30, 2008
• First Posted: May 5, 2008
• Study Start: March 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: May 1, 2010
• Last Updated: September 29, 2010

Record last verified: 2010-04

Locations

HK (1)