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

Study Overview
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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.

Official Title
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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

Conditions
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Low Gelsolin, Trauma, Infection, Burns

Intervention / Treatment
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* Drug: rhu-pGelsolin
* Drug: Placebo


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Vehicle control given as IV infusion over 1 hour<br>* Other names: Vehicle control;|
| Experimental: Low dose<br>3 mg/kg of rhu-pGelsolin given as an IV infusion over 1 hour | Drug: rhu-pGelsolin<br>* IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour<br>* Other names: Solinex;|
| Experimental: Mid-dose<br>6 mg/kg of rhu-pGelsolin given as an IV infusion over 1 hour | Drug: rhu-pGelsolin<br>* IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour<br>* Other names: Solinex;|
| Experimental: High dose<br>6 mg/kg of rhu-pGelsolin given a an IV infusion over 1 hour once a day for 3 days | Drug: rhu-pGelsolin<br>* IV formulation of recombinant plasma gelsolin formulated as 10 mg/ml given as a single IV infusion over 1 hour<br>* Other names: Solinex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of plasma gelsolin |  | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gelsolin, Trauma, Pneumonia, Peritonitis, Burn, Infection, Sepsis, Systemic Inflammatory Response Syndrome