GM-CSF Inhalation to Prevent ARDS in COVID-19 Pneumonia

Study Overview
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Brief Summary
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To assess the safety and tolerability of inhaled molgramostim nebuliser solution in patients with COVID-19 pneumonia.

Detailed Description
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COVID-19 pneumonia is induced by the newly emerging pandemic Severe acute respiratory Syndrome (SARS) coronavirus 2 and results in progression to the acute respiratory distress syndrome (ARDS). Apart from protective ventilation, fluid restriction, prone positioning and extracorporeal membrane oxygenation (ECMO), no specific therapeutic options exist to treat this devastating disease with a mortality rate of up to 50%. The growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) is widely recognized to promote differentiation and mobilization of different myeloid leukocyte subsets including neutrophils, tissue macrophages/dendritic cells or their circulating precursors. GM-CSF was found to be crucial for alveolar epithelial repair following hyperoxic and inflammatory lung injury.The aim of the current trial is to prevent progression to ARDS in COVID-19 pneumonia patients by preemptive GM-CSF Inhalation.

Official Title
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Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Inhalation to Prevent ARDS in COVID-19 Pneumonia (GI-COVID)

Conditions
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Severe Acute Respiratory Syndrome (SARS) Pneumonia, COVID-19 Pneumonia

Intervention / Treatment
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* Drug: Molgramostim nebuliser solution
* Other: Placebo nebuliser solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form by the patient according to local regulations Man or non-pregnant woman Age ≥18 years Willingness of patients with reproductive potential to use highly effective contraceptive methods by practicing abstinence or by using at least two methods of birth control from the date of consent to the end of the study. If abstinence could not be practiced, a combination of hormonal contraceptive (oral, injectable, or implants) and a barrier method (condom, diaphragm with a vaginal spermicidal agent) has to be used *. Lab-confirmed COVID-19 pneumonia where pneumonia is diagnosed by radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR clinical assessment (evidence of rales/crackles on exam) AND pulse oximeter oxygen saturation ≤ 94% at room air in patients that do not have chronic hypoxia; or less than their baseline oxygenation in patients that suffer from chronic hypoxia Negative serum pregnancy test in women of childbearing potentia Exclusion Criteria: Pregnancy or breast feeding Autoimmune thrombocytopenia, myelodysplastic syndromes with > 20% marrow blast cells History or presence of hypersensitivity or idiosyncratic reaction to molgramostim (e.g. Leucomax®) or to related compounds (e.g. Leukine®) Patient not able to use nebulizer device as well as immediately foreseeable mechanical ventilation of the patient Simultaneous participation in another clinical trial with an experimental treatment

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Molgramostim nebuliser solution<br>300μg molgramostim nebuliser solution | Drug: Molgramostim nebuliser solution<br>* 300μg molgramostim nebuliser solution nebulised seven times within 7 days via rapid nebuliser system<br>|
| Placebo Comparator: Placebo nebuliser solution<br>Placebo nebuliser solution | Other: Placebo nebuliser solution<br>* Placebo nebulised seven times within 7 days via rapid nebuliser system<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical ventilation | Need for mechanical ventilation within 15 days after randomization | During 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical status of subject at day 15 and day 29 (on a 7-point ordinal scale): | Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death. | At day 15 and day 29 | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] will be measured at day 0 (day before first dose), day 1-9, and day 15 | At day 0 (day before first dose), day 1-9, and day 15 | 
| Oxygen supply | Need for oxygen supply (l/min) to reach peripheral oxygen saturation of 98% | At day 0, day 1-7, day 8-9 (24 hours/48 hours post dose) and day 15 | 
| Clinical parameter: temperature | Clinical parameter (4 times daily): temperature (°C degree) | Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15 | 
| Clinical parameter: blood pressure | Clinical parameter (4 times daily): blood pressure (mmHg) | Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15 | 
| Clinical parameter: heart beat | Clinical parameter (4 times daily): hear beat (beats per minute) | Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15 | 
| Clinical parameter: respiratory rate | Clinical parameter (4 times daily): respiratory rate (breaths per minute) | Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15 | 
| Severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR) | Presence of Severe acute respiratory syndrome coronavirus 2 nucleic acid by PCR test in swabs or tracheal aspirates/bronchoalveolar lavage | Max. 48 hours before day 0 and at day 8-9 | 
| Laboratory: C-reactive protein test | C-reactive protein test measures the amount of C-reactive protein in blood (mg/L) | At day 0, day 1-7, day 8-9 and day 15 | 
| Laboratory: ferritin | Ferritin test measures the amount of ferritin in the blood (ng/ml) | At day 0, day 1-7, day 8-9 and day 15 | 
| Laboratory: Interleukin-6 | Interleukin-6 test (IL-6) measures the amount of IL-6 in the blood (pg/ml) | At day 0, day 1-7, day 8-9 and day 15 | 
| Laboratory: procalcitonin | Procalcitonin (PCT) test measures the amount of PCT in the blood in (μg/l) | At day 0, day 1-7, day 8-9 and day 15 | 
| Bacterial pneumonia | Occurrence of secondary bacterial pneumonia | At day 0, day 1-7, day 8-9 and day 15 | 
| Vaso-active drugs | Days on vaso-active drugs in a 29-day period | At day 29 | 
| Mortality | All-cause mortality | At day 29 | 
| GM-CSF | GM-CSF levels in serum | At day 0 and day 1-7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GM-CSF, COVID-19, ARDS