E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe pulmonary COVID-19 related disease |
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E.1.1.1 | Medical condition in easily understood language |
Severe coronavirus related lung disease |
|
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 | 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 compare the efficacy of otilimab IV versus placebo. |
|
E.2.2 | Secondary objectives of the trial |
To compare the efficacy of otilimab IV versus placebo.
To compare the safety and tolerability of otilimab IV versus placebo.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥18 years and ≤79 years at the time of obtaining informed consent.
2. Participants must:
a. have positive SARS-CoV-2 result (any validated test, e.g. RT-PCR [performed on an appropriate specimen; e.g. respiratory tract sample])
b. AND be hospitalized due to diagnosis of pneumonia (chest X-ray or computerized tomography [CT] scan consistent with COVID-19)
c. AND be developing new onset of oxygenation impairment defined as:
requiring any of the
following:
1. high-flow oxygen (≥15L/min)
2. non-invasive ventilation (e.g. CPAP, BIPAP)
3. mechanical ventilation ≤48h prior to dose
d. AND have increased biological markers of systemic inflammation (either CRP >ULN or serum ferritin >ULN).
3. No gender restriction
4. Female participants must meet and agree to abide by the contraceptive criteria detailed in the protocol.
5. Capable of giving written informed consent. If participants are not capable of giving written informed consent, alternative consent procedures will be followed. |
|
E.4 | Principal exclusion criteria |
1. Progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatments, in the opinion of the investigator.
2. Multiple organ failure according to the investigator’s judgement or a Sequential Organ Failure assessment (SOFA score) >10 if in the ICU.
3. Extracorporeal membrane oxygenation (ECMO) hemofiltration/dialysis, or high-dose (>0.15μg/kg/min) noradrenaline (or equivalent) or more than one vasopressor.
4. Current serious or uncontrolled medical condition (e.g. significant pulmonary disease [such as severe COPD or pulmonary fibrosis], heart failure [NYHA class III or higher], significant renal dysfunction, acute myocardial infarction or acute cerebrovascular accident within the last 3 months) or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study.
5. Untreated systemic bacterial, fungal, viral, or other infection (other than SARS-CoV-2).
6. Known active tuberculosis (TB), history of untreated or incompletely treated active or latent TB, suspected or known extrapulmonary TB.
7. Known HIV regardless of immunological status.
8. Known HBsAg and/or anti-HCV positive.
9. Currently receiving radiotherapy, chemotherapy or immunotherapy for malignancy.
10. Received monoclonal antibody therapy (e.g. tocilizumab, sarilumab) within the past 3 months prior to randomization, including intravenous immunoglobulin or planned to be received during the study.
11. Received immunosuppressant therapy including but not limited to cyclosporin, azathioprine, tacrolimus, mycophenolate, JAK inhibitors (e.g. baricitinib, tofacitinib, upadacitinib) within the last 3 months prior to randomization or planned to be received during the study.
12. History of allergic reaction, including anaphylaxis to any previous treatment with an anti- GM-CSF therapy.
13. Currently receiving chronic oral corticosteroids for a non-COVID-19 related condition in a dose higher than prednisone 10 mg or equivalent per day.
14. Treatment with an investigational drug within 30 days of randomization.
15. Participating in other drug clinical trials, including for COVID-19.
16. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x upper limit of normal (ULN)
17. Platelets <50,000/mm3
18. Hemoglobin ≤9 g/L
19. Absolute neutrophil count (ANC) <1.5 x 109/L (neutropenia ≥ Grade 2)
20. Estimated GFR ≤30 mL/min/1.73m2
21. Pregnant or breastfeeding females. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Participants alive and free of respiratory failure |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- All-cause mortality at Day 60
- Time to all-cause mortality up to Day 60
- Participants alive and free of respiratory failure at Day 7, 14, 42, and 60
- Time to recovery from respiratory failure up to Day 28
- Participants alive and independent of supplementary oxygen at Day 7, 14, 28, 42, and 60
- Time to last dependence on supplementary oxygen up to Day 28
- Admission to ICU up to Day 28
- Time to final ICU discharge up to Day 28
- Time to final hospital discharge up to Day 28
- Occurrence of adverse events (AEs) [up to Day 60]
- Occurrence of serious adverse events (SAEs) [up to Day 60] |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Various timepoints up to Day 60. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Argentina |
Belgium |
Brazil |
Canada |
Chile |
France |
Japan |
Mexico |
Netherlands |
Poland |
South Africa |
Spain |
Sweden |
United Kingdom |
United States |
|
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
|
The end of the study is defined as the date of the last contact of the last participant in the study. |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |