E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19 (Coronavirus RNA) |
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E.1.1.1 | Medical condition in easily understood language |
COVID-19 (A respiratory disease caused by a novel coronavirus) |
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E.1.1.2 | Therapeutic area | Health Care [N] - Environment and Public Health [N06] |
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 | 10051905 |
E.1.2 | Term | Coronavirus 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 primary objective is to compare the clinical status of patients in the remdesivir and N-saline placebo groups at Day 15 of follow-up using an ordinal outcome with 8 clinical states. Specifically, patients will be categorized into one of the following 8 mutually exclusive categories on Day 15: • Death; • Hospitalised, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO); • Hospitalised, on non-invasive ventilation or high flow oxygen devices; • Hospitalised, requiring supplemental oxygen; • Hospitalised, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); • Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; • Not hospitalized, limitation on activities and/or requiring home oxygen; • Not hospitalized, no limitations on activities.
The rationale behind this approach is to estimate in a clinically meaningful way whether the study drug has had a |
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E.2.2 | Secondary objectives of the trial |
To compare participants in the remdesivir and N-saline placebo groups for the following secondary outcomes: • Clinical Severity o Ordinal scale: - Time to an improvement of one category and two categories from Day 1 (baseline) using an ordinal scale. - Subject clinical status using ordinal scale at Days 3, 5, 8, 11, 22, and 29. - Mean change in the ordinal scale from Day 1 to Days 3, 5, 8, 11, 15, 22, and 29 • National Early Warning Score (NEWS*): - Time to discharge or to a NEWS of ≤2 and maintained for 24 hours, whichever occurs first. - Change from Day 1 to Days 3, 5, 8, 11, 15, and 29 in NEWS.
*The NEW score is a simple severity of illness scoring system that the Royal College of Physicians, UK has developed and validated. It scores physiological parameters that would be routinely collected in hospitalised patients including pulse, respiratory rate, oxygen saturation, blood pressure, pulse and level of consciousness (i.e. alert vs. not).
• Oxygenation: - Oxygenation free days |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Admitted to a hospital with symptoms suggestive of COVID-19 infection. 2. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures. 3. Understands and agrees to comply with planned study procedures. 4. Male or non-pregnant female adult ≥18 years of age at time of enrolment. 5. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay in any specimen collected < 72 hours prior to randomization. Note – 72 hours is not necessarily time from initial diagnosis. If ≥72 hours since positive PCR, the PCR may be repeated to assess eligibility. 6. Illness of any duration, and at least one of the following: Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR Clinical assessment (evidence of rales/crackles on exam) AND 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 including hormonal contraception from the time of screening through Day 29. 8. Agrees to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2.
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E.4 | Principal exclusion criteria |
1. ALT/AST > 5 times the upper limit of normal. 2. Estimated glomerular filtration rate (eGFR) < 50 or requiring dialysis. 3. Pregnancy or breast feeding. 4. Anticipated 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) |
The primary objective is to compare the clinical status of patients in the remdesivir and N-saline placebo groups at Day 15 of follow-up using an ordinal outcome with 8 clinical states. Specifically, patients will be categorized into one of the following 8 mutually exclusive categories on Day 15: • Death; • Hospitalised, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO); • Hospitalised, on non-invasive ventilation or high flow oxygen devices; • Hospitalised, requiring supplemental oxygen; • Hospitalised, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); • Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; • Not hospitalized, limitation on activities and/or requiring home oxygen; • Not hospitalized, no limitations on activities. The rationale behind this approach is to estimate in a clinically meaningful way whether the study drug has had a favourable clinical impact on the patient.
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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) |
Other endpoints include: 1) Differences in time-to-event endpoints (e.g., time to at least a one category improvement in ordinal scale) by treatment will be summarized with Kaplan-Meier curves and 95% confidence bounds. The same procedure will be used to compare time to at least a two category improvement. 2) Change in ordinal scale at specific time points will be summarized by proportions (e.g., proportion who have a 1-, 2-, 3-, or 4-point improvement or 1-, 2-, 3-, 4-point worsening). 3) Duration of event (e.g., duration of mechanical ventilation) will be summarized according to median days with quartiles. 4) Binary data (e.g., incidence of new oxygen use) will be summarized as a percent with 95% confidence intervals. Comparisons between arms will be presented as differences in proportions with 95% confidence intervals. 5) Categorical data (e.g., 28-day mortality or ordinal scale by day) may be summarized according to proportions by category and/or odds ratios with confidence intervals. |
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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 | No |
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 | 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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Italy |
Portugal |
Spain |
United Kingdom |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 1 |