Pneumonia associated Acute Respiratory Distress Syndrome (ARDS) MedDRA version: 20.0 Level: LLT Classification code 10000036 Term: A.R.D.S. System Organ Class: 100000004855
Conditions
Interventions
Product Name: Molgradex 300 mcg nebuliser solution
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: MOLGRAMOSTIM
CAS Number: 99283-10-0
Other descriptive name: Recombinant human Granulocyt
Sponsors
Justus-Liebig University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All of the following inclusion criteria must be met before the patient can enter into the trial: 1. Signed informed consent form by the patient or a legal representative according to local regulations 2. Man or woman 18 to 75 years of age, inclusive 3. Women who have been post-menopausal for more than 1 year or women of childbearing potential 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. 4. 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 5. Diagnosis of ARDS according to the Berlin ARDS definition (The ARDS definition task force) as evidenced by: a. onset within 1 week of a known clinical insult or new or worsening respiratory symptoms b. bilateral opacities on chest imaging, in the investigator’s opinion not fully explained by effusions, lobar/lung collapse, or nodules, c. respiratory failure in the investigator’s opinion not fully explained by cardiac failure or fluid overload d. PaO2/FIO2 =300 mmHg with PEEP =5 cm H2O 6. Requirement for positive pressure ventilation (non-invasive or via endotracheal tube) for more than 72 hours in total with FiO2 = 50% (or less when on additional ECMO) not longer than 14 days Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: 1. Receiving vasopressors of >100 µg/min 2. History of liver cirrhosis Child Pugh C, chronic hemodialysis (before severe pneumonia/ARDS), lung cancer 3. Malignancy with expected survival time of less than 6 months 4. History of, or listing for lung transplantation 5. Highly immunosuppressive therapy or anti-malignant combination chemotherapy within 3 weeks prior to first dose of study drug 6. Any anti-malignant chemotherapy within 24 hours prior to first dose of study drug 7. AIDS or known history of HIV infection 8. Pregnancy 9. Autoimmune thrombocytopenia, myelodysplastic syndromes with > 20% marrow blast cells 10. History or presence of hypersensitivity or idiosyncratic reaction to molgramostim or to related compounds (i.e., Growgen®, Leucomax®, Leukine™, Topleucon™) 11. Participation in another clinical trial within 90 days prior to the first dose of study drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of two different doses of inhaled molgramostim (150µg and 450µg) compared to placebo when administered to patients with pneumonia-associated ARDS, as measured by HOst defense and Pulmonary barrier rEstoration (GI-HOPE) Score.;Secondary Objective: • To assess safety and tolerability of two different doses of inhaled molgramostim (150µg and 450µg) when administered to patients with pneumonia-associated ARDS. • To assess levels of GM-CSF (in serum) after 150µg and 450µg of inhaled molgramostim compared to placebo when administered to patients with pneumonia-associated ARDS. • To assess pulmonary barrier function, systemic inflammation and improvement in morbidity in patients with pneumonia-associated ARDS treated with inhaled molgramostim. Exploratory objective: • To investigate the composition of different leucocyte subpopulations in BALF ;Primary end point(s): 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. Each parameter is given as log10 of the fold induction comparing the parameter of Day 4/5 to Day -1 and all 4 parameters are added up to a score (the value for CD206 is multiplied by (-1)). The GI-HOPE score is a surrogate marker assessing the change in BALF from Day -1 to Day 4/5.;Timepoint(s) of evaluation of this end point: The GIHOPE score is a surrogate marker assessing the change in BALF from day -1 to day 4/5 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: · Safety of dose levels/treatments · Oxygenation according to Horowitz index · Acute Physiology and Chronic Health Evaluation (APACHE) II · Sequential Organ Failure Assessment (SOFA) · Extravascular Lung Water Index (ELWI) · C-reactive protein test · Days on vaso-active drugs in a 28-day period · Days alive in a 28-day period · All-cause mortality · GM-CSF levels in serum Exploratory endpoint: Composition of different leucocyte subpopulations in BALF ;Timepoint(s) of evaluation of this end point: 28 days follow up | — |
Countries
Germany
Contacts
Public ContactProject manager
Koordinierungszentrum für Klinische Studien der Philipps-Universität Marburg (KKS Marburg)
Outcome results
None listed