Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Inhalation to Improve Host Defense and Pulmonary Barrier Restoration

Study Overview
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Brief Summary
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This trial evaluates efficacy and safety of inhaled molgramostim (rhGM-CSF) in 45 patients with pneumonia associated acute respiratory distress syndrome (ARDS). A third of the patients will receive 150 mcg inhaled molgramostim, another third 450 mcg and the remaining third will receive inhaled placebo for 3 days. The patients will be followed for 28 days.

Official Title
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GM-CSF Inhalation to Improve Host Defense and Pulmonary Barrier Restoration (GI-HOPE). A Randomized, Double-blind, Parallel Group, Multicenter, Phase II Study

Conditions
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ARDS

Intervention / Treatment
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* Drug: inhaled molgramostim (rhGM-CSF)
* Drug: inhaled placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form by the patient or a legal representative according to local regulations Man or woman 18 to 75 years of age, inclusive Women who have been post-menopausal for more than 1 year or women of childbearing potential period using a highly efficient method of contraception (i.e. a method with less than 1% failure rate such as combined hormonal contraception, progesterone-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tube occlusion, vasectomized partner, sexual abstinence) during dosing and hospitalisation. Women must have a negative serum or urine pregnancy test before the first dose of study medication and must not be lactating. Diagnosis of pneumonia-associated ARDS, where the underlying condition is Community-Acquired Pneumonia (CAP) or Hospital-Acquired Pneumonia (HAP) in patients not on invasive ventilation upon diagnosis of HAP. Diagnosis of ARDS according to the Berlin ARDS definition. Requirement for positive pressure ventilation (non-invasive or via endotracheal tube) for more than 72 hours in total with inspiratory oxygen concentration (FiO2) ≥ 50% (or less when on additional ECMO therapy) not longer than 14 days Exclusion Criteria: Receiving vasopressors of >100 µg/min History of liver cirrhosis Child Pugh C, chronic hemodialysis (before severe pneumonia/ARDS), lung cancer Malignancy with expected survival time of less than 6 months History of or listing for lung transplantation Highly immunosuppressive therapy or anti-malignant combination chemotherapy within 3 weeks prior to first dose of study drug Any anti-malignant chemotherapy within 24 hours prior to first dose of study drug AIDS or known history of HIV infection Pregnancy Autoimmune thrombocytopenia, myelodysplastic syndromes with > 20% marrow blast cells History or presence of hypersensitivity or idiosyncratic reaction to molgramostim or to related compounds (i.e., Growgen®, Leucomax®, Leukine™, Topleucon™) Participation in another clinical trial within 90 days prior to the first dose of study drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: 150 mcg inhaled molgramostim<br>once daily inhaled molgramostim (rhGM-CSF) for 3 days | Drug: inhaled molgramostim (rhGM-CSF)<br> <br> |
| Experimental: 450 mcg inhaled molgramostim<br>once daily inhaled molgramostim (rhGM-CSF) for 3 days | Drug: inhaled molgramostim (rhGM-CSF)<br> <br> |
| Placebo Comparator: inhaled placebo<br>once daily inhaled placebo for 3 days | Drug: inhaled placebo<br>* formulated as the active substance without molgramostim<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GI-HOPE score representing changes at Day 4/5 with respect to Baseline (Day -1) | The GI-HOPE score assesses change in bronchoalveolar lavage fluid (BALF) mononuclear phagocyte activation/polarization by flow cytometry (mean fluorescence intensities of parameters CD80, CD86, CD206, HLA-DR) with respect to baseline. | baseline and Day 4/5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with Adverse Events (AE), Serious AEs and Adverse Drug Reactions |  | baseline to 28 days | 
| Oxygenation | PaO2/FiO2 | Baseline to Day 11 | 
| Acute Physiology and Chronic Health Evaluation (APACHE) |  | Baseline to Day 11 | 
| Sequential Organ Failure Assessment (SOFA) |  | Baseline to Day 11 | 
| Extravascular Lung Water Index |  | Baseline to Day 11 | 
| C-reactive Protein |  | Baseline to Day 11 | 
| Days on vasoactive drugs |  | Baseline to Day 28 | 
| All cause mortality |  | Baseline to Day 28 | 
| Serum GM-CSF |  | Baseline, Days 1-4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute lung injury, molgramostim, GM-CSF, pneumonia, barrier restoration