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Severe Acute Respiratory Syndrome (SARS) PneumoniaPhase 2GI-COVIDNCT04569877

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

A Phase 2 study testing Molgramostim nebuliser solution in people with Severe Acute Respiratory Syndrome (SARS) Pneumonia and COVID-19 Pneumonia, run by University of Giessen at 9 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To assess the safety and tolerability of inhaled molgramostim nebuliser solution in patients with COVID-19 pneumonia. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Molgramostim nebuliser solution
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
63 participants
Where
9 sitesGermany
Study dates
24 Sep 2020to 20 Sep 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Germany9 sites

  • Universitätsklinikum Carl Gustav Carus Dresden

    Dresden, 01307

  • Universitätsklinikum Essen

    Essen, 45147

  • Krankenhaus Nordwest GmbH

    Frankfurt am Main, 60488

  • Universitätsklinikum Frankfurt

    Frankfurt am Main, 60590

  • Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen

    Giessen, 35392

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Universitätsklinikum Heidelberg

    Heidelberg, 69126

  • Lungenfachklinik Immenhausen

    Immenhausen, 34376

  • Sana Klinikum Offenbach

    Offenbach, 63069

Other trials in Germany

About this study

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

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

Read the detailed description

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.

Being tested
Molgramostim nebuliser solution, Placebo nebuliser solution
Keywords
GM-CSF, COVID-19, ARDS
Medical subject headings
Severe Acute Respiratory Syndrome, Pneumonia, COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Molgramostim nebuliser solutionDrug

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

  • Placebo nebuliser solutionOther

    Placebo nebulised seven times within 7 days via rapid nebuliser system

Study groups in NCT04569877
Study groupRoleWhat they receive
Molgramostim nebuliser solutionExperimental300μg molgramostim nebuliser solution
Receives: Drug: Molgramostim nebuliser solution
Placebo nebuliser solutionPlacebo comparatorPlacebo nebuliser solution
Receives: Other: Placebo nebuliser solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mechanical ventilation

    Need for mechanical ventilation within 15 days after randomization

    Measured: During 15 days

Secondary outcomes (16)

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

    1. Not hospitalized, no limitations on activities
    2. Not hospitalized, limitation on activities;
    3. Hospitalized, not requiring supplemental oxygen;
    4. Hospitalized, requiring supplemental oxygen;
    5. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
    6. Hospitalized, on invasive mechanical ventilation or ECMO;
    7. Death.

    Measured: At day 15 and day 29

  2. 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

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

  3. Oxygen supply

    Need for oxygen supply (l/min) to reach peripheral oxygen saturation of 98%

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

  4. Clinical parameter: temperature

    Clinical parameter (4 times daily): temperature (°C degree)

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

  5. Clinical parameter: blood pressure

    Clinical parameter (4 times daily): blood pressure (mmHg)

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

  6. Clinical parameter: heart beat

    Clinical parameter (4 times daily): hear beat (beats per minute)

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

  7. Clinical parameter: respiratory rate

    Clinical parameter (4 times daily): respiratory rate (breaths per minute)

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

  8. 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

    Measured: Max. 48 hours before day 0 and at day 8-9

  9. Laboratory: C-reactive protein test

    C-reactive protein test measures the amount of C-reactive protein in blood (mg/L)

    Measured: At day 0, day 1-7, day 8-9 and day 15

  10. Laboratory: ferritin

    Ferritin test measures the amount of ferritin in the blood (ng/ml)

    Measured: At day 0, day 1-7, day 8-9 and day 15

  11. Laboratory: Interleukin-6

    Interleukin-6 test (IL-6) measures the amount of IL-6 in the blood (pg/ml)

    Measured: At day 0, day 1-7, day 8-9 and day 15

  12. Laboratory: procalcitonin

    Procalcitonin (PCT) test measures the amount of PCT in the blood in (μg/l)

    Measured: At day 0, day 1-7, day 8-9 and day 15

  13. Bacterial pneumonia

    Occurrence of secondary bacterial pneumonia

    Measured: At day 0, day 1-7, day 8-9 and day 15

  14. Vaso-active drugs

    Days on vaso-active drugs in a 29-day period

    Measured: At day 29

  15. Mortality

    All-cause mortality

    Measured: At day 29

  16. GM-CSF

    GM-CSF levels in serum

    Measured: At day 0 and day 1-7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Sep 2020
  2. Study start24 Sep 2020
  3. Primary completion21 Jun 2022
  4. Study completion20 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
63 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04569877
Sponsor's protocol ID
KKS-279
Other IDs
2020-001654-21
Acronym
GI-COVID
Status last verified
Jun 2022
First submitted
25 Sep 2020
Last updated
10 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Study protocol will be provided after publication

Publications

  • 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.

    PubMed 20576718

  • 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.

    PubMed 16474098

  • 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.

    PubMed 19590023

  • 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.

    PubMed 32109013

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

    PubMed 18551128

  • 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.

    PubMed 24579839

  • 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.

    PubMed 21474645

  • 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.

    PubMed 10021465

  • 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.

    PubMed 10667491

  • 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.

    PubMed 24890235

  • 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.

    PubMed 12119223

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Molgramostim nebuliser solution in people with Severe Acute Respiratory Syndrome (SARS) Pneumonia and COVID-19 Pneumonia, run by University of Giessen at 9 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mechanical ventilation (time frame: During 15 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04569877, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023; AzTrials last refreshed its copy on 6 Nov 2026.

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