E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19 pneumonia |
COVID-19-Pneumonie |
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E.1.1.1 | Medical condition in easily understood language |
COVID-19 pneumonia |
COVID-19-Pneumonie |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10084380 |
E.1.2 | Term | COVID-19 pneumonia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the efficacy of inhaled molgramostim (300µg) compared to placebo when administered to patients with COVID-19 pneumonia in preventing progression to ARDS (= non-invasive or invasive ventilation) measured as the cumulative proportion of patients who required mechanical ventilation during a 15 days period following randomization. |
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E.2.2 | Secondary objectives of the trial |
• To assess the efficacy of inhaled molgramostin to reduce the need for oxygen supply in patients with COVID-19 pneumonia measured as the cumulative proportion of patients who required oxygen supply during a 15 days period following randomization • To assess clinical morbidity in patients with COVID-19 pneumonia treated with inhaled molgramostim comparing the change in clinical status of subject on the 7-point ordinal scale (see secondary endpoints given below) from baseline to day 15 • Mortality rate at day 15 and day 29 • To assess levels of GM-CSF in serum after 300µg of inhaled molgramostim compared to placebo when administered to patients with COVID-19 pneumonia • To assess viral loads in swabs or tracheal aspirates in patients with COVID-19 pneumonia treated with inhaled molgramostim compared to placebo • To assess safety and tolerability of inhaled molgramostim (300µg) when administered to patients with COVID-19 pneumonia
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent form by the patient according to local regulations 2. Man or non-pregnant woman 3. Age ≥18 years 4. 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 *. 5. 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 SpO2 ≤ 94% >= 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 6. Negative serum pregnancy test in women of childbearing potential
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E.4 | Principal exclusion criteria |
1. Pregnancy or breast feeding 2. Autoimmune thrombocytopenia, myelodysplastic syndromes with > 20% marrow blast cells 3. History or presence of hypersensitivity or idiosyncratic reaction to molgramostim (e.g. Leucomax®) or to related compounds (e.g. Leukine®) 4. Patient not able to use nebulizer device as well as immediately foreseeable mechanical ventilation of the patient 5. Simultaneous participation in another clinical trial with an experimental treatment
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E.5 End points |
E.5.1 | Primary end point(s) |
• Need for mechanical ventilation within 15 days after randomization |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• 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. • Safety of treatment • Need for oxygen supply (l/min) to reach peripheral oxygen saturation of 98% • Clinical parameters (3 times daily): temperature, blood pressure, heart rate, respiratory rate • Presence of SARS-CoV2 nucleic acid by PCR test in swabs or tracheal aspirates/BAL • C-reactive protein test, Ferritin, PCT • Occurrence of secondary bacterial pneumonia • Days on vaso-active drugs in a 29-day period • All-cause mortality • GM-CSF levels in serum
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 31 |
E.8.9.1 | In the Member State concerned days | |