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

COVID-19 Clinical Trial

— COV-BARRIER  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 3 Study of Baricitinib in Patients With COVID-19 Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04421027
• Other study ID #: 17830
• Secondary ID: I4V-MC-KHAA2020-
• Status: Completed
• Phase: Phase 3
• Start date: June 12, 2020
• Est. completion date: June 10, 2021

Study information

• Verified date: July 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1525
• Est. completion date: June 10, 2021
• Est. primary completion date: February 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Baricitinib
Given orally
• Placebo
Given orally

Locations

Country	Name	City	State
Argentina	Hospital Z.G.A.D "Evita Pueblo"	Berazategui	Buenos Aires
Argentina	Clinica Adventista Belgrano	Caba	Ciudad Autónoma De Buenos Aire
Argentina	Fundacion Sanatorio Guemes	Caba	Buenos Aires
Argentina	Sanatorio de la Trinidad Mitre	Caba	Buenos Aires
Argentina	ClÃ-nica Zabala	Ciudad de Buenos Aires	AR
Argentina	Sanatorio Sagrado Corazón	Ciudad de Buenos Aires	AR
Argentina	Hospital San Roque	Cordoba
Argentina	Casa Hospital San Juan de Dios	Ramos Mejía	Buenos Aires
Argentina	Hospital Interzonal General de Agudos "Eva Peron"	San Martin	Buenos Aires
Argentina	Clinica Viedma	Viedma	Río Negro
Argentina	Clinica Central S.A.	Villa Regina	Rio Negro
Brazil	Hospital Felício Rocho	Belo Horizonte	Minas Gerais
Brazil	Upeclin - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UNESP	Botucatu	São Paulo
Brazil	Hospital PUC-CAMPINAS	Campinas	São Paulo
Brazil	IPECC - Instituto de Pesquisa Clinica de Campinas	Campinas	São Paulo
Brazil	Centro Hospitalar de Reabilitacao Ana Carolina Moura Xavier	Curitiba	Parana
Brazil	CEPETI Centro de Ensino e Pesquisa em Terapia Intensiva	Curitiba	Paraná
Brazil	CECIP - Centro de Estudos do Interior Paulista	Jaú	São Paulo
Brazil	Hospital Carlos Fernando Malzoni Matao	Matao	Sao Paulo
Brazil	CPCLIN	Natal	Rio Grande Do Norte
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	RS
Brazil	Faculdade de Medicina do ABC	Santo Andre	SP
Brazil	Pesquisare	Santo Andre	Sao Paulo
Brazil	Praxis Pesquisa Medica	Santo André	Sao Paulo
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clinicos EPP Ltda	São Bernardo do Campo	São Paulo
Brazil	Casa de Saude Santa Marcelina - Centro de Pesquisa Clinica	São Paulo
Brazil	Hospital Alemão Oswaldo Cruz	São Paulo
Brazil	Hospital Santa Paula	São Paulo
Brazil	Real e Benemerita Associação Portuguesa de Beneficiencia	São Paulo
Brazil	Universidade Federal de São Paulo - Escola Paulista de Medicina	São Paulo
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Universitätsklinikum Erlangen	Erlangen	Bayern
Germany	Universitätsklinikum Schleswig-Holstein	Kiel	Schleswig-Holstein
Germany	Klinikum Rechts der Isar der TU München	München	Bayern
India	Government Medical College (GMC) Aurangabad	Aurangabad	Maharashtra
India	Medanta-The Medicity	Gurgaon	Haryana
India	Medica Superspecialty Hospital	Kolkata	West Bengal
India	Government Medical College	Nagpur	Maharashtra
India	Aakash Healthcare Super Speciality Hospital	New Delhi
India	Sir Ganga Ram Hospital	New Delhi	Delhi
India	Ruby Hall Clinic and Grant Medical Foundation	Pune	Maharashtra
India	Unity Hospital	Surat	Gujarat
Italy	Ospedale Niguarda Ca Granda	Milano
Italy	Nuovo Ospedale di Prato S. Stefano	Prato
Italy	INMI Lazzaro Spallanzani	Roma	Rome
Japan	Edogawa Medicare Hospital	Edagawa	Tokyo
Japan	Tokyo Medical University Hachioji Medical Center	Hachioji	Tokyo
Japan	Yokohama Municipal Citizen's Hospital	Yokohama	Kanagawa
Korea, Republic of	Korea University Ansan Hospital	Ansan-si	Gyeonggi-do
Korea, Republic of	Seoul Medical Center	Seoul
Korea, Republic of	Seoul National University Boramae Medical Center	Seoul	Seoul, Korea
Korea, Republic of	Ajou University Hospital	Suwon	Gyeonggi-do
Mexico	Instituto Nacional de Cardiologia Ignacio Chavez	Mexico	DF
Mexico	Instituto Nacional de Enfermedades Respiratorias	Mexico	DF
Mexico	Instituto Nacional de Cancerologia	Mexico City	FD
Mexico	Instituto Nacional de Ciencias Medicas y Nutrici Salva Zubir	Mexico City	Federal District
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo León
Mexico	ITESM Campus Monterrey	Monterrey	Nuevo Leon
Mexico	Hospital General Agustín O'Horán	Yucatan	Merida
Puerto Rico	Advanced Clinical Research, LLC	Bayamon
Russian Federation	City Clinical Hospital #15 named after O.M. Filatov	Moscow
Russian Federation	First Moscow State Medical University n.a. Sechenov	Moscow
Russian Federation	Saint-Petersburg City Pokrovskaya Hospital	Saint-Petersburg
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario Infanta Leonor-INTERNAL MED	Madrid
Spain	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcon	Madrid
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Txagorritxu	Vitoria	Alava
United Kingdom	Barnet Hospital	Barnet	Herts
United Kingdom	St. George's University Hospitals NHS Foundation Trust	London
United Kingdom	The Royal Cornwall Hospital	Truro	Cornwall
United States	Grady Health System	Atlanta	Georgia
United States	SUNY Downstate	Brooklyn	New York
United States	Great Lakes Clinical Trials	Chicago	Illinois
United States	Atlanta VA Medical Center	Decatur	Georgia
United States	Henry Ford Hospital	Detroit	Michigan
United States	Holy Cross Hospital Inc.	Fort Lauderdale	Florida
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	Dignity Health Mercy Gilbert Medical Center	Gilbert	Arizona
United States	East Carolina University	Greenville	North Carolina
United States	Community Hospital South	Indianapolis	Indiana
United States	Franciscan St. Francis Health	Indianapolis	Indiana
United States	Westchester General Hospital	Miami	Florida
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Temple Univ School of Med	Philadelphia	Pennsylvania
United States	St Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Valleywise Health	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Renown Regional Med. Center	Reno	Nevada
United States	Sharp Memorial Hospital	San Diego	California
United States	San Francisco VA Medical Center	San Francisco	California
United States	Swedish Medical Center	Seattle	Washington
United States	MultiCare Good Samaritan Hospital	Tacoma	Washington
United States	Torrance Memorial Medical Center	Torrance	California
United States	OSU Med Intl Med Houston Ctr	Tulsa	Oklahoma
United States	South Shore Hospital	Weymouth	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Germany,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Puerto Rico,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO])	Percentage of participants who die or require non-invasive ventilation/high-flow oxygen or invasive mechanical ventilation (including ECMO).	Day 1 to Day 28
Primary	Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO] Population 2	Percentage of participants who die or require non-invasive ventilation or invasive mechanical ventilation, including ECMO.	Day 1 to Day 28
Secondary	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	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.	Day 10
Secondary	Number of Ventilator-Free Days	Number of days free of invasive mechanical ventilation.	Day 1 to Day 28
Secondary	Time to Recovery	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.)	Day 1 to Day 28
Secondary	Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at 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.	Day 4
Secondary	Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at 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.	Day 7
Secondary	Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at 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.	Day 10
Secondary	Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at 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.	Day 14
Secondary	Duration of Hospitalization	Duration of hospitalization.	Days 1 to Day 28
Secondary	Percentage of Participants With a Change in Oxygen Saturation From < 94% to = 94% From Baseline	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.	Day 10
Secondary	Overall Mortality	Number of deaths by Day 28.	Day 1 to Day 28
Secondary	Duration of Stay in the Intensive Care Unit (ICU) in Days	Duration of stay in the ICU in days.	Day 1 to Day 28
Secondary	Time to Clinical Deterioration (One-category Increase on the NIAID-OS)	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.	Day 1 to Day 28
Secondary	Time to Resolution of Fever in Participants With Fever at Baseline	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).	Day 1 to Day 28
Secondary	Mean Change From Baseline on the National Early Warning Score (NEWS)	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.	Baseline, Day 4; Baseline, Day 7; Baseline, Day 10; Baseline, Day 14
Secondary	Time to Definitive Extubation	Time to definitive extubation included participants who progressed to OS 7 at any time prior to Day 28.	Day 1 to Day 28
Secondary	Time to Independence From Non-Invasive Mechanical Ventilation	Time to independence from non-invasive mechanical ventilation was measured in days among participants who required non-invasive ventilation.	Day 1 to Day 28
Secondary	Time to Independence From Oxygen Therapy in Days	Time to independence from oxygen therapy in days.	Day 1 to Day 28
Secondary	Number of Days With Supplemental Oxygen Use	Number of days with supplemental oxygen use.	Day 1 to Day 28
Secondary	Number of Days of Resting Respiratory Rate <24 Breaths Per Minute	Number of days of resting respiratory rate <24 breaths per minute.	Day 1 to Day 28

External Links

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