E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19 associated cytokine storm |
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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] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053983 |
E.1.2 | Term | Corona virus 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 |
To evaluate the efficacy (as measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit [ICU] care) of ruxolitinib + standard-of-care (SoC) therapy compared with placebo + SoC therapy, for the treatment of COVID-19 by Day 29 |
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E.2.2 | Secondary objectives of the trial |
- evaluate efficacy (as measured by composite endpoint of proportion of patients who die, develop respiratory failure, or require ICU care) of ruxolitinib + SoC therapy compared with placebo + SoC therapy, for treatment of COVID-19. - evaluate efficacy of ruxolitinib + SoC therapy compared with placebo + SoC therapy, on in-hospital outcomes in patients with COVID-19. - evaluate efficacy of ruxolitinib + SoC therapy, compared with placebo + SoC therapy, in change in NEWS2 score in patients with COVID-19. - evaluate efficacy of ruxolitinib + SoC therapy, compared with placebo + SoC therapy, in change in SpO2/FiO2 ratio in patients with COVID-19. - evaluate efficacy of ruxolitinib + SoC therapy, compared with placebo + SoC therapy, in proportion of patients with no oxygen therapy in patients with COVID-19. - evaluate safety of ruxolitinib + SoC therapy compared with placebo + SoC therapy, in treatment of patients with COVID-19. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patient or guardian/health proxy must provide informed consent (and assent if applicable) before any study assessment is performed. • Male and female patients aged >= 12 years (or >= the lower age limit allowed by Health Authority and/or Ethics Committee/Institutional Review Board approvals). • Patients with coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test or another rapid test from the respiratory tract prior to randomization. • Patients currently hospitalized or will be hospitalized prior to randomization. • Patients with lung imaging showing pulmonary infiltrates (chest Xray or CT scan) prior to randomization. • Patients, who meet at least one of the below criteria: - pulmonary infiltrates (chest X ray or chest CT scan) - Respiratory frequency >= 30/min; - Requiring supplemental oxygen; - Oxygen saturation <= 94% on room air; - Arterial oxygen partial pressure (PaO2)/ fraction of inspired oxygen (FiO2) < 300mmHg (1mmHg=0.133kPa) (corrective formulation should be used for higher altitude regions (over 1000m). |
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E.4 | Principal exclusion criteria |
• History of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib. • Presence of severely impaired renal function defined by serum creatinine > 2 mg/dL (>176.8 µmol/L), or have estimated creatinine clearance < 30 ml/min measured or calculated by Cockroft Gault equation or calculated by the updated bedside Schwartz equation. • Suspected uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19). • Currently intubated or intubated between screening and randomization. • In intensive care unit (ICU) at time of randomization. • Intubated or in ICU for COVID-19 disease prior to screening • Patients who are on anti-rejection, immunosuppressant or immunomodulatory drugs (i.e. tocilizumab, ruxolitinib, canakinumab, sarilumab, anakinra). • Unable to ingest tablets at randomization. • Pregnant or nursing (lactating) women. Additional exclusion criteria as per main section in the protocol may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
composite endpoint defined as proportion of patients who - die OR - develop respiratory failure (require mechanical ventilation) OR - require intensive care unit (ICU) care |
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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) |
1. clinical status assessed using a 9-point ordinal scale at Day 15 and Day 29 • Percentage of patients with a better category (lower number) in clinical status at Day 15 and at Day 29. • Percentage of patients with at least two-point improvement in clinical status at Day 15 and at Day 29. • Percentage of patients with at least one-point improvement in clinical status at Day 15 and at Day 29. • Percentage of patients with at least one-point deterioration in clinical status at Day 15 and at Day 29. • Time to improvement from baseline category to one less severe category of the ordinal scale. • Mean change in the 9-point ordinal scale from baseline to Days 15 and 29 2. Mortality rate at Day 15 and at Day 29; Proportion of patients requiring mechanical ventilation by Day 29; Duration of hospitalization. 3. The time to discharge or to a NEWS2 (Appendix 3) score of =2 and maintained for 24 hours whichever comes first. Change from baseline to Days 3, 5, 8, 11, 15, and 29 in NEWS2 score. 4. Change from baseline to Days 15 and 29 in SpO2/FiO2 ratio. 5. Proportion of patients with no oxygen therapy (defined as oxygen saturation = 94% on room air) at Days 15 and 29. 6. Number of participants with treatment-related adverse events (as assessed by Common Terminology Criteria for Adverse Event version 5.0), serious adverse events, clinically significant changes in laboratory measures and vital signs during the 29-day Study Period |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Day 15 and Day 29 2. Day 15 and at Day 29; Day 29 3. Days 3, 5, 8, 11, 15, and 29 4. Days 15 and 29 5. Days 15 and 29. 6. Day 29 |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | Information not present in EudraCT |
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 |
France |
Germany |
Italy |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 8 |