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    The EU Clinical Trials Register currently displays   43719   clinical trials with a EudraCT protocol, of which   7255   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
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    EudraCT Number:2014-002479-28
    Sponsor's Protocol Code Number:MOL-ARDS-002
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-04-15
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2014-002479-28
    A.3Full title of the trial
    GM-CSF Inhalation to improve HOst defense and Pulmonary barrier rEstoration
    GM-CSF Inhalation zur Verbesserung der Wirtsabwehr und der Wiederherstellung der alveolären Barrierefunktion
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    GM-CSF Inhalation to improve HOst defense and Pulmonary barrier rEstoration
    GM-CSF Inhalation zur Verbesserung der Wirtsabwehr und der Wiederherstellung der alveolären Barrierefunktion
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberMOL-ARDS-002
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorJustus-Liebig University
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportDZL (Deutsche Zentrum für Lungenforschung)
    B.4.1Name of organisation providing supportSavara ApS
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKoordinierungszentrum für Klinische Studien der Philipps-Universität Marburg (KKS Marburg)
    B.5.2Functional name of contact pointProject manager
    B.5.3 Address:
    B.5.3.1Street AddressKarl von Frisch Str.50
    B.5.3.2Town/ cityMarburg
    B.5.3.3Post code35043
    B.5.4Telephone number0049064212826503
    B.5.5Fax number0049064212866517
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameMolgradex 300 mcg nebuliser solution
    D.3.4Pharmaceutical form Nebuliser solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 99283-10-0
    D.3.9.3Other descriptive nameRecombinant human Granulocyte Macrophage Colony Stimulating Factor (rhGM-CSF)
    D.3.9.4EV Substance CodeSUB09040MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg/ml microgram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number250
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboNebuliser solution
    D.8.4Route of administration of the placeboInhalation use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pneumonia associated Acute Respiratory Distress Syndrome (ARDS)
    E.1.1.1Medical condition in easily understood language
    Patients with pneumonia-associated lung injury on pulmonary inflammation and barrier restoration.
    Patienten mit Pneumonie-assoziiertem Lungenversagen hinsichtlich pulmonaler Inflammation und Wiederherstellung der Barrierefunktion
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10000036
    E.1.2Term A.R.D.S.
    E.1.2System Organ Class 100000004855
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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.
    E.2.2Secondary objectives of the trial
    • 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
    E.2.3Trial contains a sub-study No
    E.3Principal 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
    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
    E.4Principal 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
    E.5 End points
    E.5.1Primary 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.
    E.5.1.1Timepoint(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
    E.5.2Secondary end point(s)
    Secondary endpoints:
    · Safety of dose levels/treatments
    · Oxygenation according to Horowitz index
    · Acute Physiology and Chronic Health Evaluation
    · 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

    E.5.2.1Timepoint(s) of evaluation of this end point
    28 days follow up
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    This is a randomized, double-blind, parallel group, multicenter phase II study in two parts. Part 1 is a Dose Escalation/Safety run-in part to generate safety data on two different doses of inhaled molgramostim for assessment by an IDMB. The IDMB will make recommendations whether the dose can be increased from the 150µg to 450µg dose in Part 1, and if the study can proceed to Part 2, which is a Parallel Group comparison of two different doses of inhaled molgramostim (150 and 450µg) vs placebo.
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    End of the study is defined as “Last Patient Out" and database closure.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days28
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 45
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 45
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F. of subjects incapable of giving consent
    Consent by a legal representative according to local regulations is possible
    Unterschriebene Einwilligung eines Betreuers/Vorsorgebevollmächtigten ist möglich
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state45
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 45
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-09-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-09-24
    P. End of Trial
    P.End of Trial StatusCompleted
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