E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult subjects with Covid-19 pneumonia |
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E.1.1.1 | Medical condition in easily understood language |
Adults suffering from pneumonia caused by a newly identified type of Corona virus, COVID-19 |
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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 |
Evaluation of efficacy of NuSepin® intravenous infusion in patients with SARS-CoV-2 infection |
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E.2.2 | Secondary objectives of the trial |
Evaluation of safety and tolerability of NuSepin®intravenous infusion in patients with SARS-CoV-2 infection |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects ≥18 years and < 80 years. 2. Laboratory-confirmed SARS-CoV-2 infection by PCR for the first time within 72 hours prior to randomization 3. Diagnosis of pneumonia based on: • Radiographic infiltrates by imaging (chest x-ray, CT scan) AND • 3 of the following clinical symptoms: new onset cough, fever, fatigue, sputum (all day), tachypnea, dyspnea, pleuritic chest pain AND • CRP value > 10 mg/L 4. Patients with blood leukocyte count > 4.0 x 109 /L and lymphocyte count > 0.7 x 109 /L 5. Patients with SpO2≤94% on room air or Pa02/FI02 ratio <300mgHg at screening 6. Patients capable to give consent and who have signed the informed consent form before any trial related assessment. 7. Medically accepted effective contraception for women of childbearing potential (WOCBP) which should be continued until at least 90 days after the last dose of trial treatment. |
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E.4 | Principal exclusion criteria |
1. Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal. 2. Reduced renal function with estimated glomerular filtration rate (eGFR) < 30 ml/min or hemodialysis or hemofiltration. 3. Pregnancy or breast feeding. 4. Evidence of multiorgan failure 5. Steroid treatment by any reason within 72 hours prior to enrolment 6. Participation in any other clinical trial of an experimental agent treatment for COVID-19 7. Physician makes a decision that trial involvement is not in patients' best interest, or any condition that does not allow the protocol to be followed safely. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in Time to Clinical Improvement (TTCI) [Censored at Day 29] [Time Frame: up to 29 days] between the 2 treatment and the placebo group. The primary endpoint parameter is time to clinical improvement (censored at Day 29), defined as the time (in days) from randomization of study treatment (NuSepin or placebo) until a decline of two categories on a six-category ordinal scale* of clinical status (1 ꞊ complete clinical remission; 6 ꞊ death)
* Six-category ordinal scale: 6. Death; 5. ICU, requiring ECMO and/or IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (such as LFNC or facial mask); 2. Hospitalization, not requiring supplemental oxygen; 1. Complete clinical remission, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Abbreviations: IMV= invasive mechanical ventilation; NIV= non-invasive mechanical ventilation; HFNC= High-flow nasal cannula; LFNC= Low-flow nasal cannula. |
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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) |
2.1 Efficacy endpoints: [Time Frame: up to day 14 and day 29] comparison of 3 groups for:
1. Percentage of patient s with CRP < 10 mg/L or < 30% decreases from baseline 2. Clinical status [Time Frame: days 1, 4, 9, 14 and 29] Clinical status, assessed by the six-category ordinal scale at fixed time points (days 1, 4, 9, 14 and 29). 3. Time to complete clinical remission OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours. [Time Frame: up to 29 days] 4. All-cause mortality [Time Frame: up to 29 days] 5. Duration (days) of mechanical ventilation [Time Frame: up to 29 days] 6. Duration (days) of extracorporeal membrane oxygenation [Time Frame: up to 29 days] 7. Duration (days) of supplemental oxygenation [Time Frame: up to 29 days] 8. Length of hospital stay (days) [Time Frame: up to 29 days] 9. Length of ICU stay (days) [Time Frame: up to 29 days]
2.2. Safety endpoints: incidence of treatment emergent adverse events (TEAEs) in the 3 groups |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at days 1, 4, 9, 15 and 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 | 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 | 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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 4 |
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 | No |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |