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] - 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 assess in a randomized comparison the effect of pre-emptive Tocilizumab in patients with hypoxia due to COVID-19 on 30-day mortality (from randomization) |
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E.2.2 | Secondary objectives of the trial |
To asses in a randomized comparison:
- days in hospital (calculated from randomization)
- the percentage of patients who need ICU care.
- the percentage of patients who develop respiratory failure and need mechanical ventilation
- the days on a ventilator.
- normalization of HRCT after resolution of disease
- seroconversion 14 days after randomization
- To identify potential biomarkers predictive of response (blood: cytokines (including Il-6 and IL-18), lymphopenia, CRP, ferritin, LDH, sCD25; nasal epithelial brushes: epithelial transcriptome immune response by bulk and single-cell RNA seq; faeces: microbiome, viral load), gender, age, co-morbidity and plasma levels tocilizumab by exploratory analysis.
- To assess safety and feasibility of pre-emptive use of tocilizumab (AE grade 4, increase in dyspnea according to CRS scale)
- OS after 3 months (after randomization)
- quality of life and pulmonary function after 3 months (after randomization) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
♦ Patients 18 years and older
♦ Patients with a diagnosis of COVID-19 based on a compatible clinical presentation AND a positive SARS-CoV-2 PCR on a respiratory sample such as a nasopharyngeal swab, sputum, or BAL fluid
♦ Clinical features compatible with hyperinflammation:
- Hypoxia, without other explanation for hypoxia than COVID-19 OR
- ferritin >2000 μg/L or doubling of serum ferritin in 20-48 hours
Hypoxia is defined according to ASTCT CRS Consensus grading: grade II. [Lee DW, et al. BBMT 2019;25(4):625-638] Inclusion of patients already requiring oxygen administration prior to COVID-19 should be discussed with the study team.
♦ Not be pregnant
♦ Written informed consent.
♦ Patient is capable of giving informed consent.
♦ No known allergy to tocilizumab.
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E.4 | Principal exclusion criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
♦ 30-day mortality (from randomization) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
30 days after randomization |
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E.5.2 | Secondary end point(s) |
• To asses in a randomized comparison days in hospital (calculated from randomisation).
• To asses in a randomized comparison the percentage of patients who need ICU care.
• To asses in a randomized comparison the percentage of patients who develop respiratory failure and need mechanical ventilation.
• To asses in a randomized comparison the days on a ventilator.
• To asses in a randomized comparison normalisation of HRCT after resolution of disease.
• To asses in a randomized comparison seroconversion 14 days after randomisation
• To identify potential biomarkers predictive of response (blood: cytokines (including Il-6 and IL-18), lymphopenia, CRP, ferritin, LDH, sCD25; nasal epithelial brushes: epithelial transcriptome immune response by bulk and single-cell RNA seq; faeces: microbiome, viral load), gender, age, co-morbidity and plasma levels tocilizumab by exploratory analysis.
• To assess safety and feasibility of pre-emptive use of tocilizumab (AE grade ≥4).
• To assess in a randomized comparison OS after 3 months (after randomization).
• To asses in a randomized comparison quality of life and pulmonary function after 3 months (after randomization) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to three months after randomization |
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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 | No |
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 | No |
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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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 | 3 |
E.8.9.1 | In the Member State concerned days | |