Hospitalized patients with ARDS will be randomized to intravenous treatment with a monoclonal antibody against CD14, called IC14, or placebo. They will be followed for 28 days. The primary outcome is the day 4 oxygenation index assessed as a continuous measure.
This is a phase 2, randomized, double-blind, placebo-controlled, safety and efficacy study of anti-CD14 treatment with a recombinant chimeric monoclonal antibody (IC14) in hospitalized patients with Acute Respiratory Distress Syndrome (ARDS). CD14 is a key mediator in recognition of molecular markers of tissue damage (damage-associated molecular patterns, DAMPs) and infection (pathogen-associated molecular patterns, PAMPS). The primary objective of the study is to determine the efficacy of IC14 in patients hospitalized with ARDS for reducing the severity of lung injury as measured by the day 4 Oxygenation Index (OI) assessed as a continuous measure (mean airway pressure x fraction of inspired oxygen \[FiO2\] x 100/partial pressure of oxygen \[PaO2\]). OI captures severity of hypoxemia and concurrent intensity of ventilatory support. Secondary objectives include determining whether IC14 reduces the systemic and alveolar inflammatory response, and improves indices of oxygenation and illness severity. Exploratory endpoints include determining the effect of CD14 blockade on duration of mechanical ventilation and mortality in patients hospitalized with ARDS. Pharmacokinetic \[PK\]/Pharmacodynamic \[PD\] endpoints include determining day 4 IC14 levels in bronchoalveolar fluid (BALF) vs. serum, and determining the feasibility of measuring blood presepsin levels, a CD14-pathway specific biomarker for rapid assessment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
56
monoclonal antibody against human CD14
Sterile normal saline for injection
Harborview Medical Center
Seattle, Washington, United States
RECRUITINGUniversity of Washington
Seattle, Washington, United States
RECRUITINGDay 4 Oxygenation Index
(mean airway pressure x fraction of inspired oxygen \[FiO2\] x100)/ partial pressure of oxygen \[PaO2\]
Time frame: Day 1 through Day 4
Biomarkers of injury and inflammation measured in bronchoalveolar lavage fluid
Interleukin(IL)-6
Time frame: Day 4
Biomarkers of injury and inflammation measured in plasma
Interleukin(IL)-6
Time frame: Day 4
Oxygenation index
(mean airway pressure x FiO2 x100)/PaO2
Time frame: Days 7 and 14
Oxygen saturation index
(mean airway pressure x FiO2 x100)/peripheral oxygen saturation \[SpO2\]
Time frame: Days 4, 7, and 14
P:F ratio
Ratio of partial pressure of arterial oxygen (P) to fraction of inspired oxygen (F)
Time frame: Days 4, 7, and 14
S:F ratio
Ratio of the arterial oxygen saturation (S) to fraction of inspired oxygen (F)
Time frame: Days 4, 7, and 14
Sequential Organ Failure Assessment (SOFA) Score (range 0 [best] to 24 [worst])
Disease severity scale
Time frame: Days 4, 7, and 14
Time to blood presepsin level
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time from study consent to measurement completion of blood presepsin level via the PATHFASTTM instrument
Time frame: Days 0-4
Cumulative incidence of run failures
Defined as not completing presepsin measurement between consent and infusion of study drug
Time frame: Days 0-1
Cumulative incidence of protocol-specified exempt serious events
protocol-specified exempt serious events
Time frame: Days 1-28
Cumulative incidence of grade 3 and 4 clinical and laboratory adverse events
Common Toxicity Criteria for Adverse Events version 5.0
Time frame: Days 1-28
Cumulative incidence of serious adverse events
Serious adverse events standard definition
Time frame: Days 1-28
Cumulative incidence of adverse events of special interest
Adverse events of special interest for test article and bronchoalveolar lavage
Time frame: Days 1-28