E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038700 |
E.1.2 | Term | Respiratory infection |
E.1.2 | System Organ Class | 100000004862 |
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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 |
The overall objective of the study is to evaluate the clinical efficacy and safety of different investigational therapeutics relative to the standard of care in patients hospitalized with COVID-19. |
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E.2.2 | Secondary objectives of the trial |
To evaluate clinical efficacy of different investigational therapeutics as compared to the control arm as assessed by Clinical Severity, Oxygenation, Ventilation, Hospitalisation. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject (≥18 years old) or legally authorized representative provides informed consent prior to initiation of any study procedures. When signed informed consent is not possible (e.g. due to restrictions to prevent viral transmission), verbal informed consent in the presence of a witness not related to the investigational research study will be obtained.
2. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
3. Male or non-pregnant female adult ≥18 years of age at time of enrolment.
4. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen as diagnosed within 72 hours prior to randomization.
5. Illness of any duration, and at least one of the following:
a. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), or
b. Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room air, or
c. Requiring mechanical ventilation and/or supplemental oxygen.
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E.4 | Principal exclusion criteria |
1. ALT/AST > 5 times the upper limit of normal.
2. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR < 30)
3. Pregnancy or breast feeding.
4. Allergy to any study medication
5. Any medical condition which would impose an unacceptable safety hazard by participation to the study.
6. Study drug specific exclusion criteria:
- for itraconazole: heart failure , concomitant treatment with lopinavir/ritonavir, and potent CYP450 inducers such as rifampicin, rifabutin, carbamazepine, phenobarbital, phenytoin.
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical status of subject at day 15 (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. |
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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 Severity
Oxygenation:
Mechanical Ventilation:
Hospitalization
Mortality
Evaluate the safety of the intervention through 28 days of follow-up as compared to the control arm
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |