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 | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 impact of nangibotide on the progression of disease in patients receiving ventilatory support due to Covid-19 |
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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 • To evaluate the effect of nangibotide on clinical parameters • To evaluate the safety and tolerability of nangibotide in patients with COVID 19 • 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. Admitted to an intensive care unit 4. Treatment with High Flow Nasal Oxygen, non-invasive ventilation or invasive mechanical ventilation for acute respiratory failure caused by COVID-19 for less than 48 hours 4. A PaO2:FiO2 ratio of <200mmHg (<26.7kPa) with a FiO2 ≥0.6 5. Confirmed laboratory diagnosis of COVID-19 within 7 days of meeting screening criteria
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E.4 | Principal exclusion criteria |
1. Known pregnancy (positive urine or serum pregnancy test) 2. Ongoing treatment with an immunomodulatory agent not included in the standard of care for COVID-19 (including participation in clinical trials of such agents) 3. Body mass index (BMI) ≥ 40 kg/m2 or weight ≥ 130 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) |
• Part 1: The incidence of adverse events and mortality until day 28 • Part 2: Clinical Status (7-point Ordinal Scale) assessed at Day 28 • Part 3: All-Cause mortality at 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 • The incidence of adverse events and mortality until day 28 • Safety laboratory tests (as part of routine clinical care): hematology, coagulation, plasma biochemistry • Adverse events (AEs), serious adverse events (SAEs) and deaths • Suspected adverse drug reactions (serious and non-serious)
Efficacy Parameters • Improvement of clinical status on each study day until day 14, at day 28 and at day 60 using an ordinal scale • Mortality at day 28 • PaO2:FiO2 ratio • Duration and nature of supported ventilation • Incidence of thromboembolic events • Incidence of secondary infection • Duration and nature of other organ support therapies • Functional status and mortality at day 60
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) | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
United States |
Belgium |
France |
Spain |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |