E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19-related complications |
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E.1.1.1 | Medical condition in easily understood language |
COVID-19-related complication |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
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 |
The primary objective is to determine if a specific immunomodulatory 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 determine if a specific immunomodulatory intervention reduces severity of disease as assessed by the 7-point ordinal scale • To determine if a specific immunomodulatory intervention reduces incidence of the individual endpoints of the composite • To assess the safety and efficacy of the different arms
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• be aged 18 and 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 - ≥3 if risk count includes “Radiographic severity score >3” • be considered an appropriate subject for intervention with immunomodulatory in the opinion of the investigator • be able to be maintained on venous thromboembolism prophylaxis or current maintenance therapy during inpatient dosing period, according to local guidelines
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E.4 | Principal exclusion criteria |
• Inability to supply direct informed consent from patient or from Next of Kin or Independent Healthcare Provider on behalf of patient • Mechanical ventilation at time of prior to dosing • Contraindications to study drugs, including hypersensitivity to the active substances or any of the excipients • Currently on any of the study investigational medicinal products • Known unresolved Neisseria meningitidis infection • Unwilling to be vaccinated against Neisseria meningitidis or receive prophylactic antibiotic cover until 2 weeks after vaccination • Known active tuberculosis (no blood screening required) • Known active Hepatitis B or C (no blood screening required); active varicella zoster. • Concurrent participation in any interventional clinical trial including COVID-19-related disease trials (observational studies allowed) • Patient moribund at presentation or screening • Pregnancy at screening (and 8 months after if randomised to Ravulizumab) • Unwilling to stop breastfeeding during treatment period (and 8 months after if randomised to Ravulizumab) • Alanine transaminase/aspartate transaminase (ALT/AST) > 5 times the upper limit of normal • Stage 4 severe chronic kidney disease or requiring dialysis (i.e. Cockcroft Gault estimated creatinine clearance < 30 ml /min/1.73 m^2) • Currently on a contraindicated drug (probenecid, chronic IVIG treatment) • 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to incidence (up to Day 14) of the composite endpoint of death, mechanical ventilation, Extracorporeal membrane oxygenation, cardiovascular organ support (balloon pump or inotropes), renal failure (creatinine clearance <15ml/min/1.73m2), haemofiltration or dialysis. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time from enrolment up to day 14. |
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E.5.2 | Secondary end point(s) |
• Change in clinical status assessed on 7-point ordinal scale compared to baseline • Time to each of the individual endpoints of the composite primary outcome measure • Proportion of patients with adverse events of special interest in each arm • Time to Sp02 >94% on room air (excluding chronically hypoxic individuals) • Time to first negative SARS-CoV2 PCR • Duration of oxygen therapy (days) • Duration of hospitalisation (days) • All cause mortality at day 28 • 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 |
Between enrolment and day 28 all cause mortality will be assessed. Clinical status assessed on 7-point ordinal scale by day 14. Time to clinical improvement (defined as >2 point improvement from day 1 on 7-point ordinal scale). |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 | 1 |