A Study of Baricitinib (LY3009104) in Participants With COVID-19
Condition: COVID-19
MeSH terms: COVID-19
Intervention: Baricitinib; Placebo
Intervention description: Given orally; Given orally
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1525.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: coronavirus; coronavirus infection; safety

Summary:

      The reason for this study is to see if the study drug baricitinib is effective in
      hospitalized participants with COVID-19.
    

Eligibility criteria:

        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.

        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 (started) 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.