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 | HLT |
E.1.2 | Classification code | 10022005 |
E.1.2 | Term | Influenza viral infections |
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 |
To evaluate the clinical efficacy, as assessed by time to recovery or different investigational therapeutics as compared to the control arm.
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E.2.2 | Secondary objectives of the trial |
Key Secondary: To evaluate the clincial efficacy of different investigational therapeutics relative to the control arm in adults hospitalised with COVID-19 accroding to clinical status (8-point scale) at Day 15. Additional secondary: 1. To evaluate the clinical efficaty of different invesitgational therapeutics as compared to the control arm assessed by: Clinical Severity, NEWS, Oxygenation, Non-invasive ventilation/high flow oxygen, Invasive Mechanical Ventilation/ECMO, Hospitalisation, Mortality: 14-day, 29-day. 2. To evaluate the safety of different investigational therapeutics as compared to the control arm as assessed by: Commulative incidence of SAE thorough Day 29, Commulative incidence of Grade 3 and 4 clincial and/or laboratory AEs through Day 29 Discontinuation or temporary suspension of infusions, Changes in laboratory values over time (analysis of lab. values in addition to AEs noted above Exploratory with stored samples (separate consent required) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Admitted to a hospital with synmptoms suggestive of COVID-19 infection 2. Subject (or legally authorised representative) provides informed consent prior to initiation of any study procedures 3. Subject (or legally authorised representative) understands and agrees to comply wiht planned study procedures 4.Male or non-pregnant female adult ≥ 18 years of age at time of enrollment 5. Has laboratory - confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay in any specimen as documented by either of the following: PCR positive in sample collected < 72 hours prior to randomisation OR PCR positive in sample collected ≥ 72 hours prior to randomisation, documented inabilty to obtain a repeat sample (e.g. due to lack of testing supplies limited testing capacity, results taking > 24 hours, etc.) AND progressive disease suggestive of ongoing SARS-CoV-2 infection 6. Illness of any duaration, and at least one of the following: Radiographic infiltrates by imagin (chest X-ray, CT-scanm etc.) OR SpO2 ≤ 94% on room air, OR Requiring supplemental oxygen, OR Requiring mechanical ventilation 7. Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not incluidng hormonal contraception from the time of screening through Day 29 8. Agrees to not participate in another clinical trial for treatment of COVID-19 or SARS-CoV-2 thorugh Day 29
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E.4 | Principal exclusion criteria |
1. ALT/AST > 5 times the upper limit of normal 2. Estimated glumerular filtration rate (eGFR) < 30 ml/min (inlcuding patientes receiving hemodialysis or hemofiltration) 3. Pregnancy or breast feeding 4. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours 5. Allergy to any study medication |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: Hospitalised, not requireing supplemental oxygen - no longer requires ongiong medical care Not hospitalised, limitation on activities and/or requiering home oxygen Not hospitalised, no limitations on activities Recovery is evaluated up until Day 29 Key Secondary: Death Hospitalised on invasive mechanical ventilation or ECMO Hospitalised on non-invasive ventilation or high flow oxygen devices Hospitalised, requiring supplemental oxygen Hospitallised, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalised, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalised, limitation on activities and/or requiring home oxygen Not hospitalised, no limitations on activities
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Subjects will be assessed daily while hospitalised. If the subjects discharged from the hospital they will have a study visit at Days 15, 22 and 29. For discharged subjects, it is preferred that athe Day 15 and 29 visits are in person to obtain safety laboratory tests and (for consenting subjects) OP swab and blood (serum only) samples for secondary research as well as clinical outcome data. The day 22 vist may be conducted by phone
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E.5.2 | Secondary end point(s) |
Clinical outcome assessed using ordinal scale daily while hospitalised and on Days 15, 22 and 29 NEWS assessed daily while hospitalised and on Day 15 and 29 Days of supplemental oxygen (if applicable) up to Day 29 Days of non-invasive ventilation/high flow oxygen up to Day 29 Days of invasive mechanical ventilation/ECMO (if applicable) up to Day 29 Days of hospitalisation up to Day 29 Date and cause of death (if applicable) SAEs Grade 3 and 4 AEs WBC, with differential, haemoglobin, platelets, creatinine, glucose, total bilirubin, ALT, AST, and PT on Day 1, days 3, 5, 8 and 11 (while hospitalized) and Day 15 and 29 (if attends in-person visit or still hospitalized). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Subjects will be assessed daily while hospitalised. If the subjects discharged from the hospital they will have a study visit at Days 15, 22 and 29. For discharged subjects, it is preferred that athe Day 15 and 29 visits are in person to obtain safety laboratory tests and (for consenting subjects) OP swab and blood (serum only) samples for secondary research as well as clinical outcome data. The day 22 vist may be conducted by phone
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Denmark |
Germany |
Greece |
Poland |
Spain |
United Kingdom |
United States |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |