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

NCT04569877 | Completed Phase 2

• 2 other identifiers: KKS-2792020-001654-21
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 9

Brief Summary

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

Conditions

Severe Acute Respiratory Syndrome (SARS) Pneumonia; COVID-19 Pneumonia

Keywords

GM-CSF; COVID-19; ARDS

Outcome Measures

Primary Outcomes (1)

• Mechanical ventilation

  Need for mechanical ventilation within 15 days after randomization

  During 15 days

Secondary Outcomes (16)

• Clinical status of subject at day 15 and day 29 (on a 7-point ordinal scale):

  At day 15 and day 29

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  At day 0 (day before first dose), day 1-9, and day 15

• Oxygen supply

  At day 0, day 1-7, day 8-9 (24 hours/48 hours post dose) and day 15

• Clinical parameter: temperature

  Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15

• Clinical parameter: blood pressure

  Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15

Study Arms (2)

Molgramostim nebuliser solution

EXPERIMENTAL

300μg molgramostim nebuliser solution

Drug: Molgramostim nebuliser solution

Placebo nebuliser solution

PLACEBO COMPARATOR

Placebo nebuliser solution

Other: Placebo nebuliser solution

Interventions

Molgramostim nebuliser solution DRUG

300μg molgramostim nebuliser solution nebulised seven times within 7 days via rapid nebuliser system

Molgramostim nebuliser solution

Placebo nebuliser solution OTHER

Placebo nebulised seven times within 7 days via rapid nebuliser system

Placebo nebuliser solution

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Giessen: lead

Study Sites (9)

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Krankenhaus Nordwest GmbH

Frankfurt am Main, 60488, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, 60590, Germany

Location

Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen

Giessen, 35392, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

Lungenfachklinik Immenhausen

Immenhausen, 34376, Germany

Location

Sana Klinikum Offenbach

Offenbach, 63069, Germany

Location

Related Publications (11)

• Arndt CA, Koshkina NV, Inwards CY, Hawkins DS, Krailo MD, Villaluna D, Anderson PM, Goorin AM, Blakely ML, Bernstein M, Bell SA, Ray K, Grendahl DC, Marina N, Kleinerman ES. Inhaled granulocyte-macrophage colony stimulating factor for first pulmonary recurrence of osteosarcoma: effects on disease-free survival and immunomodulation. a report from the Children's Oncology Group. Clin Cancer Res. 2010 Aug 1;16(15):4024-30. doi: 10.1158/1078-0432.CCR-10-0662. Epub 2010 Jun 24.

  PMID: 20576718 BACKGROUND

• Ballinger MN, Paine R 3rd, Serezani CH, Aronoff DM, Choi ES, Standiford TJ, Toews GB, Moore BB. Role of granulocyte macrophage colony-stimulating factor during gram-negative lung infection with Pseudomonas aeruginosa. Am J Respir Cell Mol Biol. 2006 Jun;34(6):766-74. doi: 10.1165/rcmb.2005-0246OC. Epub 2006 Feb 10.

  PMID: 16474098 BACKGROUND

• 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.

  PMID: 19590023 BACKGROUND

• Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.

  PMID: 32109013 BACKGROUND

• Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol. 2008 Jul;8(7):533-44. doi: 10.1038/nri2356.

  PMID: 18551128 BACKGROUND

• 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.

  PMID: 24579839 BACKGROUND

• 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.

  PMID: 21474645 BACKGROUND

• LeVine AM, Reed JA, Kurak KE, Cianciolo E, Whitsett JA. GM-CSF-deficient mice are susceptible to pulmonary group B streptococcal infection. J Clin Invest. 1999 Feb;103(4):563-9. doi: 10.1172/JCI5212.

  PMID: 10021465 BACKGROUND

• Matute-Bello G, Liles WC, Radella F 2nd, Steinberg KP, Ruzinski JT, Hudson LD, Martin TR. Modulation of neutrophil apoptosis by granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor during the course of acute respiratory distress syndrome. Crit Care Med. 2000 Jan;28(1):1-7. doi: 10.1097/00003246-200001000-00001.

  PMID: 10667491 BACKGROUND

• 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.

  PMID: 24890235 BACKGROUND

• Presneill JJ, Harris T, Stewart AG, Cade JF, Wilson JW. A randomized phase II trial of granulocyte-macrophage colony-stimulating factor therapy in severe sepsis with respiratory dysfunction. Am J Respir Crit Care Med. 2002 Jul 15;166(2):138-43. doi: 10.1164/rccm.2009005.

  PMID: 12119223 BACKGROUND

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome; Pneumonia; COVID-19

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral

Study Officials

• Susanne Herold, Prof. Dr.

  Universitätsklinikum Giessen und Marburg (UKGM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2020
• First Posted: September 30, 2020
• Study Start: September 24, 2020
• Primary Completion: June 21, 2022
• Study Completion: September 20, 2022
• Last Updated: May 10, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 3 Months after publication
• Access Criteria: Central server

Locations

DE (9)