Inhaled GM-CSF for Respiratory Virus-Associated Severe Pneumonia

Study Overview
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Brief Summary
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This study will investigate the safety and efficacy of the administration of inhaled GM-CSF to patients with respiratory virus-associated pneumonia.

Official Title
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A Phase I Study of Inhaled GM-CSF in the Treatment of Respiratory Virus-associated Severe Pneumonia

Conditions
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Acute Respiratory Distress Syndrome, Pneumonia, Respiratory Virus Infection

Intervention / Treatment
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* Drug: Sargramostim 0.04 mcg/kg/dose
* Drug: Sargramostim 0.2mcg/kg/dose
* Drug: Sargramostim 1 mcg/kg/dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Individuals must meet all of the following criteria to be eligible for inclusion in this study: Male or female Age ≥ 18 years and ≤ 80 years Able to understand and willing to sign a written informed consent document, or if incapacitated, has a designated legal representative who is able to understand and willing to sign a written informed consent document Able and willing to adhere to study visit schedule and study procedures Currently either oro-tracheally or naso-tracheally intubated Diagnosis of respiratory viral infection determined by: Polymerase Chain Reaction (PCR)-based Respiratory Virus Panel (RVP) positive for at least one of the following: Respiratory syncytial virus (RSV) Influenza A/B Parainfluenza 1/2/3 Human Metapneumovirus Adenovirus Rhinovirus Exclusion criteria Individuals meeting any of the following criteria will be excluded from participating in this study. Active tracheostomy History of either autoimmune PAP or primary genetic PAP diagnosis History of the presence of histopathologically- or radiographically-documented, clinically significant pulmonary fibrosis History of clinically significant cardiovascular disease including but not limited to Congestive heart failure associated with New York Heart Association (NYHA) Functional Classification of >1 (i.e., with any degree of symptoms) History of typical or atypical angina within the past 6 months regardless of possible relief by nitrates History of clinically significant coagulopathy, bleeding diathesis, or other hematological disease History of severe allergic or anaphylactic reaction to sargramostim, other yeast-derived products, or any component of the study drug History of any other serious medical condition that, in the opinion of the Principal Investigator, would interfere with the ability of the patient to complete the study Concomitant current or recent prior use of specific medications including Lithium, either active or prior use within two weeks of screening and/or enrollment Active non-steroidal anti-inflammatory drug use, including but not limited to ibuprofen Women who are pregnant (i.e. have a positive serum pregnancy test), intending to become pregnant, breast feeding, or women of child-bearing potential who are unwilling to use contraception or maintain abstinence during the course of the study History of active tobacco/marijuana/e-cigarette use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Interventional Model Description: Phase I, open label dose escalation study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerosolized Sargramostim<br>A self-controlled, open-label study to evaluate safety of Sargramostim administered by nebulization | Drug: Sargramostim 0.04 mcg/kg/dose<br>* The final dilution of sargramostim will occur at the bedside by a study team member. Cohort 1 will receive sargramostim 0.04 mcg/kg/dose nebulized to the inspiratory loop of the patients' mechanical ventilator circuit for 15 minutes.<br>* Other names: Cohort 1;Drug: Sargramostim 0.2mcg/kg/dose<br>* The final dilution of sargramostim will occur at the bedside by a study team member. Cohort 1 will receive sargramostim 0.2 mcg/kg/dose nebulized to the inspiratory loop of the patients' mechanical ventilator circuit for 15 minutes.<br>* Other names: Cohort 2;Drug: Sargramostim 1 mcg/kg/dose<br>* The final dilution of sargramostim will occur at the bedside by a study team member. Cohort 1 will receive sargramostim 1 mcg/kg/dose nebulized to the inspiratory loop of the patients' mechanical ventilator circuit for 15 minutes.<br>* Other names: Cohort 3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events of Inhaled Sargramostim in Adult Patients with Severe Respiratory Viral Pneumonia | The occurrence of any treatment-emergent Adverse Events (AE's) or Serious Adverse Events (SAE's) will be recorded over the course of the trial. | 1 year |