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 | 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 |
To evaluate the safety and tolerability of nangibotide in mechanically ventilated patients due to Covid-19 and features of systemic inflammation |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effects of nangibotide exposure over 5 days in patients with Covid-19 and features of systemic inflammation • To evaluate the effect of nangibotide on clinical parameters • To evaluate PD relationship to TREM-1 pathway related markers • To evaluate the natural history of the disease regarding the activation of the TREM-1 pathways measured by soluble TREM-1 serum concentrations over time
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provide written informed consent (emergency consent according to local regulations where approved) 2. Age 18 to 75 years (inclusive) 3. Mechanically-ventilated patient for acute respiratory distress caused by COVID-19 4. Confirmed laboratory diagnosis of COVID-19 within 7 days of meeting screening criteria 5. Laboratory markers of severity met <24 hours after blood sample collection for at least one of the following within 7 days after the initiation of mechanical ventilation: • C Reactive Protein > 40 mg/L OR • Ferritin >500 µg/L OR • Lymphocyte count of <1.0x10e9/L
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E.4 | Principal exclusion criteria |
1. Invasive mechanical ventilation for more than 7 days 2. Known pregnancy (positive urine or serum pregnancy test) 3. Weight > 95 kg 4. Anticipated transfer to another hospital, which is not a study site within 72 hours 5. Expected to die within 6 months of treatment due to underlying chronic disease 6. Limitations of care in place during current hospital admission |
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E.5 End points |
E.5.1 | Primary end point(s) |
The incidence of adverse events and mortality until day 28 |
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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) |
Additional Safety Parameters • Safety laboratory tests (as part of routine clinical care): hematology, coagulation, plasma biochemistry • Adverse events (AEs), serious adverse events (SAEs) and deaths Efficacy Parameters • Clinical status defined by seven-point and ordinal scale at baseline (day 1), day 6 and 14 following initiation of treatment and day 28 • Mortality at day 28 • PaO2:FiO2 ratio • Duration and nature of mechanical ventilation • Duration and nature of other organ support therapies Pharmacodynamics (exploratory) sTREM-1, inflammatory exploratory biomarkers |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 |
Belgium |
France |
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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The end of study is defined as the last patient, last visit (LPLV) at day 28. |
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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 | |
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 months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |