| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| COVID-19 after infection with SARS-CoV-2 |
| COVID-19 efter infektion med Ny Coronavirus |
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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 |
|
| 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 aim of this study is to evaluate the efficacy and safety of convalescent anti-SARS-CoV-2 plasma, hydroxychloroquine, sarilumab and baricitinib compared with placebo in combination with standard of care (SOC) for the treatment of moderate-to-severe COVID-19 pneumonia on the basis of the composite endpoint: All-cause mortality or need of invasive mechanical ventilation up to 28 days. |
| Formålet med forsøget er at undersøge, om én eller flere af i alt 4 typer af behandling til patienter indlagt med moderat-svær lungebetændelse forårsaget af den nye coronavirus SARS-CoV-2 er mere effektivt til at mildne sygdomsforløbet og forhindre alvorlig sygdom end understøttende behandling alene. |
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
● ≥18 years of age
● Confirmed COVID-19 infection per WHO criteria / presence of SARS-CoV-2 nucleic acid by polymerase chain reaction (PCR)
● Evidence of pneumonia given by at least one of the following:
○ SpO2 ≤93% on ambient air or PaO2/FiO2 <300 mmHg/40 kPa
○ Radiographic findings compatible with COVID-19 pneumonia
● Onset of first experienced symptom, defined as one respiratory symptom or fever, no more than 10 days before admission
● For women of childbearing potential: Negative pregnancy test and willingness to use contraceptive (consistent with local regulations) during study period
● Signed Informed Consent Form by any patient capable of giving consent, or, when the patient is not capable of giving consent, by his or her legal/authorized representative
|
● Alder ≥18 år
● Bekræftet COVID-19 infektion
● Mindst én af følgende tegn på lungebetændelse:
○ Iltmætning under 94%
○ Fund på røntgen af brystkassen forenelig med COVID-19 infektion i lungerne
● Symptomdebut max 10 dage før indlæggelse
● For kvinder i den fertile alder skal der foreligge en negativ graviditetstest, og der skal anvendes prævention gennem hele studieperioden
● Signeret informeret samtykkeerklæring af patienten selv eller af en legal repræsentant for patienten i tilfælde af inhabil patient
|
|
| E.4 | Principal exclusion criteria |
● In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment
● History of allergic reaction to study drug (as judged by the site investigator)
● Participating in other drug clinical trials (participation in COVID-19 antiviral trials may be permitted if approved by sponsor)
● Pregnant or breastfeeding, positive pregnancy test in a pre-dose examination or patients family planning within three months after receiving study agent
● Estimated glomerular filtration (eGFR) <30 ml/min
● Severe liver dysfunction (Child Pugh score C)
● Known history of the following medical conditions:
○ Active or latent tuberculosis (TB) or history of incompletely treated TB
○ Chronic hepatitis B or C infection
○ Retinopathy or maculopathy
○ Neurogenic hearing impairment
● Presence of any of the following abnormal laboratory values at screening:
○ Absolute neutrophil count (ANC) less than 1000 mm3 (= 1,0 x 10⁹ /L)
○ Alanine aminotransferase (ALT) greater than 5 x upper limit of normal (ULN)
○ Platelet count <50,000 per mm3 (= 50 x 10⁹ /L)
● Immunosuppression, defined as following:
○ Treatment with immunosuppressive agents, chemotherapy or immunomodulatory drugs within 30 days prior to inclusion
○ Use of chronic oral corticosteroids for a non-COVID-19-related condition in a dose higher than prednisolone 20 mg or equivalent per day for 4 weeks
○ Ongoing chemotherapy
● Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in and completion of the study
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● Nært forestående død (inden for de følgende 24 timer) uafhængigt af behandlingstiltag, efter investigators vurdering
● Kendt allergi over for én eller flere af forsøgsbehandlingerne
● Deltagelse i et andet behandlingsforsøg (dog vil deltagelse i andre COVID-19 antivirale forsøg evt. tillades, hvis sponsor godkender dette)
● Graviditet eller amning
● Nedsat nyrefunktion (svarende til estimeret glomerulær filtrationsrate <30 ml/min)
● Svær leverdysfunktion (svarende til Child Pugh score C)
● Kendt med følgende sygdomme:
○ Aktivt eller latent tuberkulose
○ Kronisk infektion med hepatitis B eller C
○ Øjensygdom (i form af retinopati eller makulopati)
○ Neurogen hørenedsættelse
● Tilstedeværelse af én eller flere af de følgende abnorme laboratorieværdier:
○ Neutrofile leukocytter < 1,0 x 10⁹ /L
○ Alanin-aminotransferase > 5 x øvre normalgrænse
○ Blodplader < 50 x 10⁹ /L
● Immunsuppression, defineret som:
○ Behandling med immunosuppressive midler, kemoterapi eller immunmodulerende midler inden for 30 dage forud for inklusion
○ Langvarig behandling med binyrebarkhormon (svarende til >20 mg prednisolon per dag i >4 uger)
● Enhver alvorlig medicinsk tilstand eller abnorm laboratorietest, som efter investigators vurdering er uforenelig med opretholdelse af patients sikkerhed ved deltagelse i studiet
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary outcome is a composite endpoint: All-cause mortality or need of invasive mechanical ventilation up to 28 days. |
| Det primære endepunkt er et sammensat endepunkt bestående af 1) mortalitet eller 2) behov for mekanisk ventilation frem til dag 28. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
● Frequency of adverse events
● Frequency of severe adverse events
● Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status
● Ventilator-free days to day 28
● Organ failure-free days to day 28
● Duration of ICU stay
● Mortality rate at days 7, 14, 21, 28, and 90
● Length of hospital stay
● Duration of supplemental oxygen |
| De sekundære endepunkter er: Frekvens af bivirkninger og alvorlige bivirkninger, bedring i funktionsniveau, antal dage uden respirator til dag 28, antal dage uden organsvigt til dag 28, antal dage på intensiv afsnit, antal dage med ilttilskud, længden af hospitalsindlæggelse samt mortalitetsraten på dag 7, 14, 21, 28 og 90. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| See individual timepoints E.5.2. |
| Se individuelle tidspunkter E.5.2. |
|
| 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) | No |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | 6 |
| 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 | 12 |
| 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 | 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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| 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 | 2 |
| E.8.9.1 | In the Member State concerned days | |
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