Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Inhalation to Improve Host Defense and Pulmonary Barrier Restoration

NCT02595060 | Completed Phase 2 DMC

• 1 other identifier: MOL-ARDS-002
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

Brief Summary

This trial evaluates efficacy and safety of inhaled molgramostim (rhGM-CSF) in 45 patients with pneumonia associated acute respiratory distress syndrome (ARDS). A third of the patients will receive 150 mcg inhaled molgramostim, another third 450 mcg and the remaining third will receive inhaled placebo for 3 days. The patients will be followed for 28 days.

Conditions

ARDS

Keywords

acute lung injury, molgramostim, GM-CSF, pneumonia, barrier restoration

Outcome Measures

Primary Outcomes (1)

• GI-HOPE score representing changes at Day 4/5 with respect to Baseline (Day -1)

  The GI-HOPE score assesses change in bronchoalveolar lavage fluid (BALF) mononuclear phagocyte activation/polarization by flow cytometry (mean fluorescence intensities of parameters CD80, CD86, CD206, HLA-DR) with respect to baseline.

  baseline and Day 4/5

Secondary Outcomes (9)

• Number of patients with Adverse Events (AE), Serious AEs and Adverse Drug Reactions

  baseline to 28 days

• Oxygenation

  Baseline to Day 11

• Acute Physiology and Chronic Health Evaluation (APACHE)

  Baseline to Day 11

• Sequential Organ Failure Assessment (SOFA)

  Baseline to Day 11

• Extravascular Lung Water Index

  Baseline to Day 11

Study Arms (3)

150 mcg inhaled molgramostim

EXPERIMENTAL

once daily inhaled molgramostim (rhGM-CSF) for 3 days

Drug: inhaled molgramostim (rhGM-CSF)

450 mcg inhaled molgramostim

EXPERIMENTAL

once daily inhaled molgramostim (rhGM-CSF) for 3 days

Drug: inhaled molgramostim (rhGM-CSF)

inhaled placebo

PLACEBO COMPARATOR

once daily inhaled placebo for 3 days

Drug: inhaled placebo

Interventions

inhaled molgramostim (rhGM-CSF) DRUG

150 mcg inhaled molgramostim; 450 mcg inhaled molgramostim

inhaled placebo DRUG

formulated as the active substance without molgramostim

inhaled placebo

Eligibility Criteria

• Age: 18 Years - 75 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 or a legal representative according to local regulations
• Man or woman 18 to 75 years of age, inclusive
• Women who have been post-menopausal for more than 1 year or women of childbearing potential period using a highly efficient method of contraception (i.e. a method with less than 1% failure rate such as combined hormonal contraception, progesterone-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tube occlusion, vasectomized partner, sexual abstinence) during dosing and hospitalisation. Women must have a negative serum or urine pregnancy test before the first dose of study medication and must not be lactating.
• Diagnosis of pneumonia-associated ARDS, where the underlying condition is Community-Acquired Pneumonia (CAP) or Hospital-Acquired Pneumonia (HAP) in patients not on invasive ventilation upon diagnosis of HAP.
• Diagnosis of ARDS according to the Berlin ARDS definition.
• Requirement for positive pressure ventilation (non-invasive or via endotracheal tube) for more than 72 hours in total with inspiratory oxygen concentration (FiO2) ≥ 50% (or less when on additional ECMO therapy) not longer than 14 days

You may not qualify if:

• Receiving vasopressors of \>100 µg/min
• History of liver cirrhosis Child Pugh C, chronic hemodialysis (before severe pneumonia/ARDS), lung cancer
• Malignancy with expected survival time of less than 6 months
• History of or listing for lung transplantation
• Highly immunosuppressive therapy or anti-malignant combination chemotherapy within 3 weeks prior to first dose of study drug
• Any anti-malignant chemotherapy within 24 hours prior to first dose of study drug
• AIDS or known history of HIV infection
• Pregnancy
• Autoimmune thrombocytopenia, myelodysplastic syndromes with \> 20% marrow blast cells
• History or presence of hypersensitivity or idiosyncratic reaction to molgramostim or to related compounds (i.e., Growgen®, Leucomax®, Leukine™, Topleucon™)
• Participation in another clinical trial within 90 days prior to the first dose of study drug

Sponsors & Collaborators

• University of Giessen: lead

Study Sites (7)

Klinik und Poliklinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie

Würzburg, Baden-Würtemberg, 97080, Germany

Location

Universitätsklinikum Frankfurt, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie

Frankfurt, 60590, Germany

Location

Universities of Marburg and Giessen Lung Center

Giessen, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover, Klinik für Pneumologie

Hanover, 30625, Germany

Location

Universitätsklinikum Jena, Klinik für Anästhesiologie und Intensivmedizin

Jena, 07747, Germany

Location

University Hospital Marburg, Department of Anaesthesiology and Intensive Care Medicine

Marburg, Germany

Location

Related Publications (5)

• 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

• 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

• 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.

  PMID: 22996662 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

• Standiford LR, Standiford TJ, Newstead MJ, Zeng X, Ballinger MN, Kovach MA, Reka AK, Bhan U. TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial pneumonia. Am J Physiol Lung Cell Mol Physiol. 2012 Mar 1;302(5):L447-54. doi: 10.1152/ajplung.00415.2010. Epub 2011 Dec 9.

  PMID: 22160309 BACKGROUND

MeSH Terms

Conditions

Acute Lung Injury; Pneumonia

Interventions

regramostim

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Infections

Study Officials

• Susanne Herold, Prof.Dr.med.,PhD

  Universities of Giessen and Marburg Lung Centers, Germany

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 1, 2015
• First Posted: November 3, 2015
• Study Start: June 1, 2016
• Primary Completion: September 22, 2021
• Study Completion: July 31, 2022
• Last Updated: August 31, 2023

Record last verified: 2023-08

Locations

DE (7)