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 | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
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 |
To determine if a specific intervention reduces the composite of progression of patients with COVID-19-related disease to organ failure or death. |
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E.2.2 | Secondary objectives of the trial |
To identify the pharmacodynamic effects of therapies on biomarkers known to be associated with progression of CRC.
To identify pharmacodynamic effects of the therapies based on their mechanisms of action.
To determine if a specific intervention reduces severity of disease as assessed by the 7-point ordinal scale.
To determine if a specific intervention reduces incidence of the individual endpoints of the composite.
To assess the safety and efficacy of the different arms.
To identify the pharmacodynamic effects of therapies on relevant biomarkers
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be included in the trial the participant must: • be aged 18 or over • have clinical picture strongly suggestive of COVID-19-related disease (with/without positive COVID-19 test) AND - Risk count (as defined above) >3 OR - Risk count >=3 if it includes “Radiographic severity score >3” • be considered an appropriate subject for intervention with immunomodulatory or other disease modifying agents in the opinion of the investigator • Is able to swallow capsules/tablets
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E.4 | Principal exclusion criteria |
The presence of any of the following will preclude participant inclusion:
• Inability to supply direct informed consent from patient or from Next of Kin or Independent Healthcare Provider on behalf of patient • Invasive mechanical ventilation at time of screening • Contraindications to study drugs, including hypersensitivity to the active substances or any of the excipients • Currently on any of the study investigational medicinal products • Concurrent participation in an interventional clinical trial (observational studies allowed) • Patient moribund at presentation or screening • Pregnancy at screening • Unwilling to stop breastfeeding during treatment period • Known severe hepatic impairment (with or without cirrhosis) • Stage 4 severe chronic kidney disease or requiring dialysis (i.e. Cockcroft Gault estimated creatinine clearance < 30 ml /min) • Inability to swallow at screening visit • Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the patient ineligible for inclusion because of a safety concern. • Patient is taking a systemic immunosuppressive agent such as, but not limited to, oral steroids, methotrexate, azathioprine, ciclosporin or tacrolimus, unless these are given as part of COVID standard of care treatment. • Type 1 diabetes • Known idiopathic pulmonary fibrosis • Previous hospital admission with ketoacidosis • History of symptomatic heart failure within 3 months of admission • Sustained blood pressure below 90/60 mmHg at admission • Metabolic acidosis defined as pH< 7.25 (or venous bicarbonate <15 mmol/l) AND ketones > 3.0 mmol/L • Alanine transaminase and/or aspartate transaminase (ALT and/or AST) > 3 times the upper limit of normal (only one needs to be measured)
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to incidence (up to Day 14) of any one of the following:
o Death o Invasive mechanical ventilation o ECMO o Cardiovascular organ support (balloon pump or inotropes/ vasopressors) o Renal failure (Cockcroft-Gault estimated creatinine clearance <15 ml /min), haemofiltration or dialysis
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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) |
1. Biomarkers thought to be associated with progression of COVID-19: Ferritin, CRP, D-Dimer, neutrophil to lymphocyte ratio, LDH 2. Change in clinical status as assessed on 7-point ordinal scale compared to baseline 3. Time to each of the individual endpoints of the composite primary outcome measure 4. Proportion of patients with adverse events of special interest in each arm 5. SpO2/FiO2 6. Time to Sp02 >94% on room air (excluding chronically hypoxic individuals) 7. Time to first negative SARS-CoV2 PCR 8. Duration of oxygen therapy (days) 9. Duration of hospitalisation (days) 10.All-cause mortality at day 28 11.Time to clinical improvement (defined as >2 point improvement from day 1 on 7-point ordinal scale) |
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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 | Information not present in EudraCT |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 14 |
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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The end of trial is 18 months after LPLV. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 30 |