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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10084460 |
E.1.2 | Term | COVID-19 treatment |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
Primary objectives: Safety Objective: • To evaluate the safety of CovenD24 in the treatment of patients with moderate or severe COVID-19.
Primary Efficacy Objectives: • To determine the minimally effective dose, as assessed by the improvement in the respiratory rate and oxygen saturation. • To determine the effect of each dose on inflammatory markers. |
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E.2.2 | Secondary objectives of the trial |
Secondary Efficacy Objectives: • To evaluate time to improvement and recovery (COVID-19 clinical severity score of 3 or lower). • To evaluate respiratory failure [defined as an arterial oxygen pressure (PaO2) of <60 mmHg and/or an arterial carbon dioxide pressure (PaCO2) of >45 mmHg, or the need for mechanical ventilation, extracorporeal membrane oxygenation (ECMO), non-invasive ventilation (NIV), high-flow oxygen devices] rate. • To evaluate the death rate. • To evaluate time from hospitalization to hospital discharge. • To assess the COVID-19-related symptoms through an investigator interview. • To evaluate the effect of CovenD24 on the SpO2/FiO2 ratio. Exploratory Objective: Blood samples for interleukin 6 (IL-6) and other cytokines will be stored for future analysis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. A COVID-19 diagnosis confirmed with a SARS-CoV-2 infection positive polymerase chain reaction (PCR) test within 30 days from screening. 2. Age 18-80 years. 3. Severity of disease according to the following criteria (at least one clinical parameter and one laboratory parameter are required): a. Clinical and Imaging-based evaluation i. Respiratory rate > 23/min and < 30/min ii. SpO2 at room air ≤94% and ≥90% iii. Bilateral pulmonary infiltrates >25% within 24-48 hours or a severe deterioration compared to imaging at admission. b. Evidence of an exacerbated inflammatory process i. LDH ≥300 U/L or what is the upper limit for normal per age ii. CRP ≥25 mg/L iii. Ferritin ≥500 ng/ml iv. Lymphocytes <800 cells/mm3 v. D-dimers ≥500ng/ml 4. Willing and able to sign an informed consent. |
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E.4 | Principal exclusion criteria |
1. Any concomitant illness that, based on the judgment of the Investigator might affect the interpretation or the results of the study (i.e., immunodeficiency). 2. Mechanically-ventilated patient or patient who will probably require ICU admission or mechanical ventilation within 24 hours from enrolment, according to the Investigator’s judgment. 3. Previous complete or partial vaccination for SARS-CoV-2. 4. Pregnancy [positive urine pregnancy test (women of childbearing potential only)] or breastfeeding. 5. Participation in any other Interventional study in the last 30 days 6. Active Cancer |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Safety Endpoints: • Incidence of treatment (dose)-related serious adverse events. • Incidence of all adverse events related or unrelated to the study treatment. Primary Efficacy Endpoints: • Proportion of patients with respiratory rate < 23/min for at least 24 hours, on Day 7. • Proportion of patients with SpO2 saturation >94%, on room air for at least 24 hours, on Day 7. • Proportion of patients with a decrease by 50% in either CRP/LDH/Fibrinogen/Ferritin/D-dimers from baseline to Day 7. |
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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) |
Secondary Efficacy Endpoints: • Rate of categorical and absolute score improvement of COVID-19 status on Day 7 improving from “Severe” to at least “Moderate” or from “Moderate” to “Moderate-Mild” using any of the COVID-19 clinical severity ordinal scales as described in protocol, in each dose group and the total population. • Time to recovery, measured from enrolment (Day 1) to recovery or last follow-up (Day 28). Recovery is defined as achieving the "ambulatory mild disease" classification as described in protocol. • Death rate at end of study (Day 28). • Proportion of patients with no mechanical ventilation (ECMO, NIV, high flow) on Day 7. • Proportion of patients with haemodynamic instability or requiring vasopressors on Day 7. • Change in the SpO2/FiO2 ratio on Day 7. • Time to death or respiratory failure (defined as an arterial oxygen pressure (PaO2) of <60 mmHg and/or an arterial carbon dioxide pressure (PaCO2) of >45 mmHg, or the need for mechanical ventilation, ECMO, non-invasive ventilation, or high-flow oxygen devices) within 28 days of the study period (Day 1 to Day 28). • Hospital discharge time within 28 days of the study period, calculated from the day of randomization (Day 1) to discharge or last follow-up (Day 28), whichever comes first. • Proportion of patients requiring admission to an Intensive-Care Unit (ICU) on Day 7. • Proportion of patients with respiratory rate < 23/min for 24 hours at every visit until Day 28, inclusive. • Proportion of patients with change [decrease/no change (±2 breaths/min)/improvement] in respiratory rate from baseline to Day 7. • Proportion of patients with SpO2 >94% on room air, for at least 24 hours at every visit until Day 28, inclusive. • Proportion of patients with change [decrease/no change (±2 %)/improvement] in SpO2 saturation from baseline to Day 7. • Proportion of patients with an increase of 25% in the absolute lymphocyte count, sustained for ≥24 hours on Day 7. • Change in absolute lymphocyte count from baseline to Day 7. • Proportion of patients with a decrease of 20% in the neutrophil-to-lymphocyte ratio (NLR), sustained for ≥24 hours on Day 7. • Change in NLR from baseline to Day 7. • Percentage of patients within each severity rating on the ordinal scale within 28 days of the study period (Day 1 to Day 28). • Time to improvement in the categorical and ordinal scale, measured from randomization (Day 1) to last study follow-up (Day 28). • Change in the COVID-19 clinical severity ordinal scale from baseline [before-treatment assessment (Screening/Day 1)] up to Day 28. • Change from baseline in the score of the Assessment of 14 Common COVID-19-Related Symptoms, as assessed through an Investigator interview (2). • Change in the flow rate of supplemental oxygen administration over time. • The duration of supplemental (non-invasive) oxygen administration.
Exploratory Endpoint: • Blood samples for interleukin 6 (IL-6) and other cytokines will be stored for future analysis. |
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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 | 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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Different dose of the same IMP |
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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 | 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 | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 4 |