Inhaled GM-CSF for Respiratory Virus-Associated Severe Pneumonia

NCT ID: NCT02601365

Last Updated: 2023-06-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-31

Study Completion Date

2019-05-31

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.

Detailed Description

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Conditions

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Acute Respiratory Distress Syndrome Pneumonia Respiratory Virus Infection

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Phase I, open label dose escalation study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Aerosolized Sargramostim

A self-controlled, open-label study to evaluate safety of Sargramostim administered by nebulization

Group Type EXPERIMENTAL

Sargramostim 0.04 mcg/kg/dose

Intervention Type DRUG

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.

Sargramostim 0.2mcg/kg/dose

Intervention Type DRUG

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.

Sargramostim 1 mcg/kg/dose

Intervention Type DRUG

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.

Interventions

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Sargramostim 0.04 mcg/kg/dose

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.

Intervention Type DRUG

Sargramostim 0.2mcg/kg/dose

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.

Intervention Type DRUG

Sargramostim 1 mcg/kg/dose

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.

Intervention Type DRUG

Other Intervention Names

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Cohort 1 Cohort 2 Cohort 3

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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Milton S. Hershey Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

References

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Thomas NJ, Shaffer ML, Willson DF, Shih MC, Curley MA. Defining acute lung disease in children with the oxygenation saturation index. Pediatr Crit Care Med. 2010 Jan;11(1):12-7. doi: 10.1097/PCC.0b013e3181b0653d.

Reference Type BACKGROUND
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Cakarova L, Marsh LM, Wilhelm J, Mayer K, Grimminger F, Seeger W, Lohmeyer J, Herold S. Macrophage tumor necrosis factor-alpha induces epithelial expression of granulocyte-macrophage colony-stimulating factor: impact on alveolar epithelial repair. Am J Respir Crit Care Med. 2009 Sep 15;180(6):521-32. doi: 10.1164/rccm.200812-1837OC. Epub 2009 Jul 9.

Reference Type BACKGROUND
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Huang FF, Barnes PF, Feng Y, Donis R, Chroneos ZC, Idell S, Allen T, Perez DR, Whitsett JA, Dunussi-Joannopoulos K, Shams H. GM-CSF in the lung protects against lethal influenza infection. Am J Respir Crit Care Med. 2011 Jul 15;184(2):259-68. doi: 10.1164/rccm.201012-2036OC. Epub 2011 Apr 7.

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Sever-Chroneos Z, Murthy A, Davis J, Florence JM, Kurdowska A, Krupa A, Tichelaar JW, White MR, Hartshorn KL, Kobzik L, Whitsett JA, Chroneos ZC. GM-CSF modulates pulmonary resistance to influenza A infection. Antiviral Res. 2011 Nov;92(2):319-28. doi: 10.1016/j.antiviral.2011.08.022. Epub 2011 Sep 8.

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Ghoneim HE, Thomas PG, McCullers JA. Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections. J Immunol. 2013 Aug 1;191(3):1250-9. doi: 10.4049/jimmunol.1300014. Epub 2013 Jun 26.

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Steinwede K, Tempelhof O, Bolte K, Maus R, Bohling J, Ueberberg B, Langer F, Christman JW, Paton JC, Ask K, Maharaj S, Kolb M, Gauldie J, Welte T, Maus UA. Local delivery of GM-CSF protects mice from lethal pneumococcal pneumonia. J Immunol. 2011 Nov 15;187(10):5346-56. doi: 10.4049/jimmunol.1101413. Epub 2011 Oct 14.

Reference Type BACKGROUND
PMID: 22003204 (View on PubMed)

Unkel B, Hoegner K, Clausen BE, Lewe-Schlosser P, Bodner J, Gattenloehner S, Janssen H, Seeger W, Lohmeyer J, Herold S. Alveolar epithelial cells orchestrate DC function in murine viral pneumonia. J Clin Invest. 2012 Oct;122(10):3652-64. doi: 10.1172/JCI62139. Epub 2012 Sep 10.

Reference Type BACKGROUND
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Paine R 3rd, Standiford TJ, Dechert RE, Moss M, Martin GS, Rosenberg AL, Thannickal VJ, Burnham EL, Brown MB, Hyzy RC. A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury. Crit Care Med. 2012 Jan;40(1):90-7. doi: 10.1097/CCM.0b013e31822d7bf0.

Reference Type BACKGROUND
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Luisetti M, Kadija Z, Mariani F, Rodi G, Campo I, Trapnell BC. Therapy options in pulmonary alveolar proteinosis. Ther Adv Respir Dis. 2010 Aug;4(4):239-48. doi: 10.1177/1753465810378023. Epub 2010 Jul 20.

Reference Type BACKGROUND
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Trapnell BC, Carey BC, Uchida K, Suzuki T. Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages. Curr Opin Immunol. 2009 Oct;21(5):514-21. doi: 10.1016/j.coi.2009.09.004. Epub 2009 Sep 30.

Reference Type BACKGROUND
PMID: 19796925 (View on PubMed)

Tazawa R, Trapnell BC, Inoue Y, Arai T, Takada T, Nasuhara Y, Hizawa N, Kasahara Y, Tatsumi K, Hojo M, Ishii H, Yokoba M, Tanaka N, Yamaguchi E, Eda R, Tsuchihashi Y, Morimoto K, Akira M, Terada M, Otsuka J, Ebina M, Kaneko C, Nukiwa T, Krischer JP, Akazawa K, Nakata K. Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis. Am J Respir Crit Care Med. 2010 Jun 15;181(12):1345-54. doi: 10.1164/rccm.200906-0978OC. Epub 2010 Feb 18.

Reference Type BACKGROUND
PMID: 20167854 (View on PubMed)

Herold S, Hoegner K, Vadasz I, Gessler T, Wilhelm J, Mayer K, Morty RE, Walmrath HD, Seeger W, Lohmeyer J. Inhaled granulocyte/macrophage colony-stimulating factor as treatment of pneumonia-associated acute respiratory distress syndrome. Am J Respir Crit Care Med. 2014 Mar 1;189(5):609-11. doi: 10.1164/rccm.201311-2041LE. No abstract available.

Reference Type BACKGROUND
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Papiris SA, Tsirigotis P, Kolilekas L, Papadaki G, Papaioannou AI, Triantafillidou C, Papaporfyriou A, Karakatsani A, Kagouridis K, Griese M, Manali ED. Long-term inhaled granulocyte macrophage-colony-stimulating factor in autoimmune pulmonary alveolar proteinosis: effectiveness, safety, and lowest effective dose. Clin Drug Investig. 2014 Aug;34(8):553-64. doi: 10.1007/s40261-014-0208-z.

Reference Type BACKGROUND
PMID: 24890235 (View on PubMed)

Other Identifiers

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PSHCH0001

Identifier Type: -

Identifier Source: org_study_id

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