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] - 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 |
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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 |
To evaluate the effect of baricitinib 4 mg once daily (QD) compared to placebo on disease progression in patients with COVID-19 infection |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of baricitinib 4 mg QD compared to placebo on clinical outcomes in patients with COVID-19 infection |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Hospitalized with coronavirus (SARS-CoV-2) infection, confirmed by polymerase chain reaction (PCR) test or other commercial or public health assay in any specimen, as documented by either of the following: • PCR positive in sample collected <72 hours prior to randomization; OR • PCR positive in sample collected ≥72 hours prior to randomization (but no more than 14 days prior to randomization), documented inability to obtain a repeat sample (for example, due to lack of testing supplies, limited testing capacity, results taking >24 hours, etc.) AND progressive disease suggestive of ongoing SARS-CoV-2 infection. - Requires supplemental oxygen at the time of study entry and at randomization. - Have indicators of risk of progression: at least 1 inflammatory markers >upper limit of normal (ULN) (C reactive protein [CRP], D dimer, lactate dehydrogenase [LDH], ferritin) with at least 1 instance of elevation >ULN within 2 days before study entry. |
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E.4 | Principal exclusion criteria |
- Are receiving cytotoxic or biologic treatments (such as tumor necrosis factor [TNF] inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], T-cell or B-cell targeted therapies (rituximab), interferon, or Janus kinase (JAK) inhibitors for any indication at study entry. Note: A washout period 4 weeks (or 5 half-lives, whichever is longer) is required prior to screening. - Have ever received convalescent plasma or intravenous immunoglobulin [IVIg]) for COVID-19. - Have received high dose corticosteroids at doses >20 mg per day (or prednisone equivalent) administered for >=14 consecutive days in the month prior to study entry. - Strong inhibitors of OAT3 (such as probenecid) that cannot be discontinued at study entry. - Have received neutralizing antibodies, such as bamlanivimab, casirivimab and imdevimab for COVID-19. - Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening tests required). - Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product. - Have received any live vaccine within 4 weeks before screening, or intend to receive a live vaccine during the study. Note: Use of nonlive (inactivated) vaccinations is allowed for all participants. - Require invasive mechanical ventilation, including extracorporeal membrane oxygenation (ECMO) at study entry. - Current diagnosis of active malignancy that, in the opinion of the investigator, could constitute a risk when taking investigational product. - Have a history of venous thromboembolism (VTE) (deep vein thrombosis [DVT] and /or pulmonary embolism [PE]) within 12 weeks prior to randomization or have a history of recurrent (>1) VTE (DVT/PE). - Anticipated discharge from the hospital, or transfer to another hospital (or another unit), which is not a study site within 72 hours after study entry. - Have neutropenia (absolute neutrophil count <1000 cells/microliters) - Have lymphopenia (absolute lymphocyte count <200 cells/microliters) - Have alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times ULN - Estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease [MDRD]) <30 milliliter/minute/1.73 meters squared. - Have a known hypersensitivity to baricitinib or any of its excipients. - Are currently enrolled in any other clinical study involving an investigation product or any other type of medical research judged not to be scientifically or medically compatible with this study. Note: The participant should not be enrolled (start) in another clinical trial for the treatment of COVID-19 or SARS CoV-2 through Day 28. - Are pregnant, or intend to become pregnant or breastfeed during the study. - Are using or will use extracorporeal blood purification (EBP) device to remove proinflammatory cytokines from the blood such as a cytokine absorption or filtering device, for example, CytoSorb®. - Are, in the opinion of the investigator, unlikely to survive for at least 48 hours after screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (including extracorporeal membrane oxygenation [ECMO]). |
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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.Percentage of Participants with at Least 1-Point Improvement on NIAID-OS or Live Discharge from Hospital. The National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS) is an assessment of clinical status. The scale is as follows: Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities. 2.Number of Ventilator-Free Days 3.Time to Recovery (Recovery assessed by the NIAID-OS) 4.Overall Improvement on the NIAID-OS 5.Duration of Hospitalization 6.Percentage of Participants with a Change in Oxygen Saturation from <94% to ≥94% from Baseline 7.Mortality 8.Duration of Stay in the Intensive Care Unit (ICU) in Days 9.Time to Clinical Deterioration (one-category increase on the NIAID-OS) 10.Time to Resolution of Fever, in Participants with Fever at Baseline 11. Mean Change from Baseline on the National Early Warning Score (NEWS). The NEWS is used to detect and report changes in illness severity in participants with acute illness. The score is determined from six physiological parameters readily measured over time in hospitalized participants: Respiration rate; oxygen saturation; temperature; systolic blood pressure; heart (pulse) rate, and level of consciousness 12.Time to Definitive Extubation 13.Time to Independence from Non-Invasive Mechanical Ventilation 14.Time to Independence from Oxygen Therapy in Days 15.Number of Days with Supplemental Oxygen Use 16.Number of Days of Resting Respiratory Rate <24 Breaths per Minute |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary endpoints will be evaluated [Day 1 to Day 28], except: endpoint 1 and 6 [Day 10], endpoint 11 [Baseline, Day 1 to Day 28]. |
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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 | Yes |
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 | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Germany |
Italy |
Japan |
Mexico |
Russian Federation |
Spain |
United Kingdom |
United States |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |