A Study of Baricitinib (LY3009104) in Participants With COVID-19

Phase 3

Completed

Conditions: COVID-19

Interventions: Drug: Placebo
Drug: Baricitinib

Registration Number: NCT04421027

Lead Sponsor: Eli Lilly and Company

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1525

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + SOC	Placebo	Placebo (given as two placebo tablets) administered orally QD with standard of care.
Baricitinib + Standard of Care (SOC)	Baricitinib	4 milligrams (mg) of baricitinib (given as two 2 mg tablets) administered orally every day (QD) with standard of care.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO])	Day 1 to Day 28	Percentage of participants who die or require non-invasive ventilation/high-flow oxygen or invasive mechanical ventilation (including ECMO).
Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO] Population 2	Day 1 to Day 28	Percentage of participants who die or require non-invasive ventilation or invasive mechanical ventilation, including ECMO.

Secondary Outcome Measures

Name	Time	Method
Duration of Hospitalization	Days 1 to Day 28	Duration of hospitalization.
Percentage of Participants With at Least 1-Point Improvement on National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) or Live Discharge From Hospital	Day 10	The National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS) is an assessment of clinical status. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 8) Death. Participants with missing baseline ordinal scale values were excluded from analysis.
Number of Ventilator-Free Days	Day 1 to Day 28	Number of days free of invasive mechanical ventilation.
Time to Recovery	Day 1 to Day 28	Recovery assessed by the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS). Time to reach NIAID-OS 1, 2, or 3 for the first time. The date reached is the first full day that OS 1, 2, or 3 is the participant's maximum OS for the day. NIAID-OS 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities and/or requiring home oxygen 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.)
Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4	Day 4	Overall improvement on the National Institute of Allergy and Infectious Diseases ordinal scale: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5. Hospitalized, requiring supplemental oxygen; 6.Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 8. Death.
Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7	Day 7	Overall improvement on the National Institute of Allergy and Infectious Diseases ordinal scale: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5. Hospitalized, requiring supplemental oxygen; 6.Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 8. Death.
Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10	Day 10	Overall improvement on the National Institute of Allergy and Infectious Diseases ordinal scale: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5. Hospitalized, requiring supplemental oxygen; 6.Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 8. Death.
Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14	Day 14	Overall improvement on the National Institute of Allergy and Infectious Diseases ordinal scale: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5. Hospitalized, requiring supplemental oxygen; 6.Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 8. Death.
Percentage of Participants With a Change in Oxygen Saturation From < 94% to ≥ 94% From Baseline	Day 10	Percentage of participants with a change in oxygen saturation from \< 94% to ≥ 94% from baseline based on National Early Warning Score (NEWS). Measure of the oxygen level of the blood is measure by pulse oximetry. 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, as measured by Alert Voice Pain Unresponsive (AVPU). A score is assigned to each parameter, the magnitude of the score representing the extremity of variation from the norm. A weighting score is added for participants needing supplemental oxygen (oxygen delivery by mask or by cannula) The aggregate score is reflective of the participants status.
Overall Mortality	Day 1 to Day 28	Number of deaths by Day 28.
Duration of Stay in the Intensive Care Unit (ICU) in Days	Day 1 to Day 28	Duration of stay in the ICU in days.
Time to Clinical Deterioration (One-category Increase on the NIAID-OS)	Day 1 to Day 28	The National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS) is an assessment of clinical status. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 8) Death. A higher score is representative of worse clinical outcome with a score of 8 being the highest and representing death.
Time to Resolution of Fever in Participants With Fever at Baseline	Day 1 to Day 28	Time to resolution of fever in participants with fever at baseline was calculated using cox proportional hazard regression model adjusted for baseline disease severity (OS 4, OS 5, OS 6), age (\<65 years, \>=65 years), region (United States, Europe, rest of world), and systemic corticosteroids used at baseline for primary study condition (Yes/No).
Time to Independence From Non-Invasive Mechanical Ventilation	Day 1 to Day 28	Time to independence from non-invasive mechanical ventilation was measured in days among participants who required non-invasive ventilation.
Time to Independence From Oxygen Therapy in Days	Day 1 to Day 28	Time to independence from oxygen therapy in days.
Mean Change From Baseline on the National Early Warning Score (NEWS)	Baseline, Day 4; Baseline, Day 7; Baseline, Day 10; Baseline, Day 14	The NEWS score is used to detect and report changes in illness severity in participants with acute illness to identify participants at risk for poor outcomes. The score is based on six physiological parameters (Respiration rate; oxygen saturation; temperature; systolic blood pressure; heart (pulse) rate, and level of consciousness). A score is assigned to each parameter, and the sum of the score represents the participant's risk of poor outcomes with a minimum score of 0 representing the better outcome, a score of 7 or greater reflects high clinical risk for worsening and maximum score of 19 representing the worse outcome.
Number of Days With Supplemental Oxygen Use	Day 1 to Day 28	Number of days with supplemental oxygen use.
Number of Days of Resting Respiratory Rate <24 Breaths Per Minute	Day 1 to Day 28	Number of days of resting respiratory rate \<24 breaths per minute.
Time to Definitive Extubation	Day 1 to Day 28	Time to definitive extubation included participants who progressed to OS 7 at any time prior to Day 28.

Trial Locations

Locations (96): Dignity Health Mercy Gilbert Medical Center
🇺🇸
Gilbert, Arizona, United States
Valleywise Health
🇺🇸
Phoenix, Arizona, United States
St Joseph's Hospital and Medical Center
🇺🇸
Phoenix, Arizona, United States
Hoag Memorial Hospital Presbyterian
🇺🇸
Newport Beach, California, United States
Sharp Memorial Hospital
🇺🇸
San Diego, California, United States
San Francisco VA Medical Center
🇺🇸
San Francisco, California, United States
Torrance Memorial Medical Center
🇺🇸
Torrance, California, United States
Holy Cross Hospital Inc.
🇺🇸
Fort Lauderdale, Florida, United States
Westchester General Hospital
🇺🇸
Miami, Florida, United States
Grady Health System
🇺🇸
Atlanta, Georgia, United States
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Dignity Health Mercy Gilbert Medical Center
🇺🇸Gilbert, Arizona, United States