A Phase 2 Study of IC14 in Acute Respiratory Distress Syndrome

Study Overview
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Brief Summary
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Acute Respiratory Distress Syndrome (ARDS) patients will be randomized to receive either IC14 (a single dose of 4 mg/kg followed by 2 mg/kg on Days 2-4) or placebo. Study participation will be for a total of 28 days.

Detailed Description
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Up to 160 patients with ARDS will be randomized to receive either IC14 at a dosage of 4 mg/kg on Study Day 1, then 2 mg/kg once daily on Study Days 2-4 or placebo for 4 days beginning within 48 hours of meeting inclusion criteria. Study participation will be for 28 days.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Preliminary Efficacy Study of IC14 in Acute Respiratory Distress Syndrome

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: IC14
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ICU admission Age 18-70 years Presence of a known ARDS clinical risk within 7 days of onset: Pneumonia Sepsis Trauma Aspiration Pancreatitis Presence of ARDS (per Berlin criteria) defined as follows: Acute onset (<48 hours) PaO2/FiO2<300 on PEEP≥5 Bilateral opacities consistent with pulmonary edema on frontal chest radiograph not fully explained by effusions, lobar/lung collapse, or nodules. Requirement for positive pressure ventilation via endotracheal tube Anticipated duration of mechanical ventilation >48 hrs Exclusion Criteria: Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry Intubation for cardiopulmonary arrest Do-not-attempt resuscitation (DNAR) status Intubation for status asthmaticus, pulmonary embolus, myocardial infarction Anticipated survival <48 hours from intubation Anticipated survival <28 days due to pre-existing medical condition Significant pre-existing organ dysfunction Lung: Currently receiving home oxygen therapy as documented in medical record Heart: Pre-existing congestive heart failure defined as an ejection fraction <20% as documented in the medical record Renal: Chronic renal failure requiring renal replacement therapy Liver: Severe chronic liver disease defined as Child-Pugh Class C Pre-existing, ongoing immunosuppression Solid organ transplant recipient Chronic high-dose corticosteroids (equivalent to >20 mg/prednisone/day for >14 days in the last 30 days) Oncolytic drug therapy within the past 14 days Known HIV positive with CD4 count <200 cells/mm3 Current treatment with Enbrel® (etanercept), Remicade® (infliximab), Humira® (adalimumab), Cimzia® (certolizumab), or Simponi® (golimumab), Kineret® (anakinra), or Arcalyst® (rilonacept) Pregnancy History of hypersensitivity or idiosyncratic reaction to IC14 Deprivation of freedom by administrative or court order

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IC14<br>IC14 4 mg/kg IV on Study Day 1, then IC14 2 mg/kg IV once daily on Study Days 2-4. | Drug: IC14<br>* Blocks CD14 signalling which is responsible for disease pathogenesis in ARDS<br>* Other names: monoclonal antibody against CD14;|
| Placebo Comparator: Placebo<br>Placebo IV once daily on Study Day 1-4 | Other: Placebo<br>* sterile normal saline for infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | The number of toxicities and adverse events that are attributable to treatment. The safety parameters will include an evaluation of the clinical signs and symptoms from the history and physical exam, vital signs, adverse events, and laboratory findings. Immunogenicity studies will measure antibodies against IC14. | 28 days | 
| Ventilator-free days | The number of days alive and free of mechanical ventilation through Day 28. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ARDS biologic markers. | Change in plasma IL-8, sTNFR1, IL-6 from Day 0 to Day 4 Change in alveolar neutrophils and total protein from Day 0 to Day 4 | 28 days |