E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Covid19 is characterized by hypoxemic respiratory failure, caused by extensive vascular leak and pulmonary edema early in the course of disease. |
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E.1.1.1 | Medical condition in easily understood language |
Pulmonary vascular leakage of fluids into the lungs |
longschade door COVID-19 infectie |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
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 test whether treatment with oral imatinib reduce disease burden and consumption of medical resources. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to evaluate the pharmacokinetics and immunomodulatory actions of a 10-day course of oral imatinib in patients with severe COVID-19 disease. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >18 years - Hospital admission with proven SARS2-Covid19 infection - Hypoxemic respiratory failure (SaO2 <94%, PaO2 <9kPa) - Ability to give informed consent.
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E.4 | Principal exclusion criteria |
- Pre-existing chronic pulmonary disease - Former diagnosis of Interstitial pulmonary disease - Former diagnosis of COPD 4 or FEV1<30%pred - Previous DLCO <45% - Total lung capacity (TLC) < 60% of predicted - Lung cancer with non-surgical treatment in last year - Chronic home oxygen treatment - Pre-existing heart failure with a known left ventricular ejection fraction <40% - Active treatment of hematological or non-hematological cancer with targeted, immuno- or chemotherapy or targeted radiotherpay in the last year - Inability to provide informed consent - Any subject who had received any investigational medication within 1 month prior to the start of this study or who is scheduled to receive another investigational drug during the course of this study - Active liver disease, porphyria or elevations of serums transaminases >5 x ULN (upper limit of normal) or bilirubin > 1.5 x ULN - History or suspicion of inability to cooperate adequately. - White blood count < 4.0^109/l - Hemoglobin < 6.0 mmol/l - Thrombocytes < 100^109/l - Pregnant female subjects - Breastfeeding female subjects - Use of strong Cyp3A4 inductors, including the following drugs: Carbamazepine, efavirenz, enzalutamide, fenobarbital, fenytoine, hypericum, mitotaan, nevirapine, primidon, rifabutine, rifampicine - Concomittant use of chloroquine or hydroxychloroquine. - QTc >500msec at baseline.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to liberation from ventilation and supplemental oxygen >48h while being alive during a 28-day period 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) |
- Secondary efficacy parameters o 28-day mortality o Need for ICU admission o Length of ICU admission o Need for invasive ventilation o Length of invasive ventilation o Days on ventilator o Need for ECMO o Need for non-invasive ventilation o Length of non-invasive ventilation o SpO2 at Day 1,2,3,4,5,7,9 o Fi O2 at Day 1,2,3,4,5,7,9 o SpO2/FiO2 at Day 1,2,3,4,5,7,9 - Safety parameters o Blood cell count Day 0,1,2,3,5,7,9 o Kidney function Day 0,1,2,3,5,7,9 o Liver enzymes Day 0,1,2,3,5,7,9 o NTproBNP at Day 0,1,2,3,5,7,9 o SAEs / AE o ECG at Day 1,3,5,9 - Pharmacokinetics o Study drug plasma levels at 4h, 8h, Day 1,3,5,7,9 o Albumin, AGP1 at Day 0,1,2,3,5,7,9 - Immune responses (subgroups of 50 patients per study arm) o Host response plasma biomarkers on day 0, 5 and 9, and on the first day of any additional interventions (invasive ventilation, CT scanning, bronchoscopy). o Neutrophil RNA sequencing, metabolomics and lipidomics on day 0 and 5 o Phenotypic and functional analysis of whole blood, peripheral blood mononuclear cells and polymorphonuclear leukocytes on day 0 and 5, and on the first day of additional interventions (invasive ventilation, CT scanning, bronchoscopy). - Fibrotic responses (subgroups of 50 patients per study arm) o Fibrotic plasma biomarkers on day 0, 5 and 9, and on the first day of any additional interventions (invasive ventilation, CT scanning, bronchoscopy) |
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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 | Yes |
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) | Yes |
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 | 15 |
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 | 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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |