Clinical trial NCT04421027: A Study of Baricitinib (LY3009104) in Participants With COVID-19
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 3 Study of Baricitinib in Patients With COVID-19 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: coronavirus
coronavirus infection
safety
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2020-06-09
Enrollment: 1525
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO])
timeFrame: Day 1 to Day 28
measure: Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO] Population 2
timeFrame: Day 1 to Day 28
Secondary outcomes:
measure: 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
timeFrame: Day 10
measure: Number of Ventilator-Free Days
timeFrame: Day 1 to Day 28
measure: Time to Recovery
timeFrame: Day 1 to Day 28
measure: Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4
timeFrame: Day 4
measure: Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7
timeFrame: Day 7
measure: Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10
timeFrame: Day 10
measure: Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14
timeFrame: Day 14
measure: Duration of Hospitalization
timeFrame: Days 1 to Day 28
measure: Percentage of Participants With a Change in Oxygen Saturation From < 94% to ≥ 94% From Baseline
timeFrame: Day 10
measure: Overall Mortality
timeFrame: Day 1 to Day 28
measure: Duration of Stay in the Intensive Care Unit (ICU) in Days
timeFrame: Day 1 to Day 28
measure: Time to Clinical Deterioration (One-category Increase on the NIAID-OS)
timeFrame: Day 1 to Day 28
measure: Time to Resolution of Fever in Participants With Fever at Baseline
timeFrame: Day 1 to Day 28
measure: Mean Change From Baseline on the National Early Warning Score (NEWS)
timeFrame: Baseline, Day 4; Baseline, Day 7; Baseline, Day 10; Baseline, Day 14
measure: Time to Definitive Extubation
timeFrame: Day 1 to Day 28
measure: Time to Independence From Non-Invasive Mechanical Ventilation
timeFrame: Day 1 to Day 28
measure: Time to Independence From Oxygen Therapy in Days
timeFrame: Day 1 to Day 28
measure: Number of Days With Supplemental Oxygen Use
timeFrame: Day 1 to Day 28
measure: Number of Days of Resting Respiratory Rate <24 Breaths Per Minute
timeFrame: Day 1 to Day 28
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Dignity Health Mercy Gilbert Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Valleywise Health
state: Arizona
city: Phoenix
country: United States
facility: St Joseph's Hospital and Medical Center
state: Arizona
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Francisco
country: United States
facility: San Francisco VA Medical Center
state: California
city: Torrance
country: United States
facility: Torrance Memorial Medical Center
state: California
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital Inc.
state: Florida
city: Miami
country: United States
facility: Westchester General Hospital
state: Florida
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Decatur
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Chicago
country: United States
facility: Great Lakes Clinical Trials
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Regional Medical Center
state: Indiana
city: Indianapolis
country: United States
facility: Community Hospital South
state: Indiana
city: Indianapolis
country: United States
facility: Franciscan St. Francis Health
state: Indiana
city: Weymouth
country: United States
facility: South Shore Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Reno
country: United States
facility: Renown Regional Med. Center
state: Nevada
city: Brooklyn
country: United States
facility: SUNY Downstate
state: New York
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Tulsa
country: United States
facility: OSU Med Intl Med Houston Ctr
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Temple Univ School of Med
state: Pennsylvania
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Tacoma
country: United States
facility: MultiCare Good Samaritan Hospital
state: Washington
city: Ciudad de Buenos Aires
country: Argentina
facility: Sanatorio Sagrado Corazón
state: AR
city: Ciudad de Buenos Aires
country: Argentina
facility: ClÃ-nica Zabala
state: AR
city: Berazategui
country: Argentina
facility: Hospital Z.G.A.D "Evita Pueblo"
state: Buenos Aires
city: Caba
country: Argentina
facility: Sanatorio de la Trinidad Mitre
state: Buenos Aires
city: Caba
country: Argentina
facility: Fundacion Sanatorio Guemes
state: Buenos Aires
city: Ramos Mejía
country: Argentina
facility: Casa Hospital San Juan de Dios
state: Buenos Aires
city: San Martin
country: Argentina
facility: Hospital Interzonal General de Agudos "Eva Peron"
state: Buenos Aires
city: Caba
country: Argentina
facility: Clinica Adventista Belgrano
state: Ciudad Autónoma De Buenos Aire
city: Villa Regina
country: Argentina
facility: Clinica Central S.A.
state: Rio Negro
city: Viedma
country: Argentina
facility: Clinica Viedma
state: Río Negro
city: Cordoba
country: Argentina
facility: Hospital San Roque
city: Belo Horizonte
country: Brazil
facility: Hospital Felício Rocho
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Centro Hospitalar de Reabilitacao Ana Carolina Moura Xavier
state: Parana
city: Curitiba
country: Brazil
facility: CEPETI Centro de Ensino e Pesquisa em Terapia Intensiva
state: Paraná
city: Natal
country: Brazil
facility: CPCLIN
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: RS
city: Matao
country: Brazil
facility: Hospital Carlos Fernando Malzoni Matao
state: Sao Paulo
city: Santo Andre
country: Brazil
facility: Pesquisare
state: Sao Paulo
city: Santo André
country: Brazil
facility: Praxis Pesquisa Medica
state: Sao Paulo
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina do ABC
state: SP
city: Botucatu
country: Brazil
facility: Upeclin - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UNESP
state: São Paulo
city: Campinas
country: Brazil
facility: IPECC - Instituto de Pesquisa Clinica de Campinas
state: São Paulo
city: Campinas
country: Brazil
facility: Hospital PUC-CAMPINAS
state: São Paulo
city: Jaú
country: Brazil
facility: CECIP - Centro de Estudos do Interior Paulista
state: São Paulo
city: São Bernardo do Campo
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clinicos EPP Ltda
state: São Paulo
city: São Paulo
country: Brazil
facility: Real e Benemerita Associação Portuguesa de Beneficiencia
city: São Paulo
country: Brazil
facility: Hospital Alemão Oswaldo Cruz
city: São Paulo
country: Brazil
facility: Universidade Federal de São Paulo - Escola Paulista de Medicina
city: São Paulo
country: Brazil
facility: Hospital Santa Paula
city: São Paulo
country: Brazil
facility: Casa de Saude Santa Marcelina - Centro de Pesquisa Clinica
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: München
country: Germany
facility: Klinikum Rechts der Isar der TU München
state: Bayern
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
state: Schleswig-Holstein
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
state: Delhi
city: Surat
country: India
facility: Unity Hospital
state: Gujarat
city: Gurgaon
country: India
facility: Medanta-The Medicity
state: Haryana
city: Aurangabad
country: India
facility: Government Medical College (GMC) Aurangabad
state: Maharashtra
city: Nagpur
country: India
facility: Government Medical College
state: Maharashtra
city: Pune
country: India
facility: Ruby Hall Clinic and Grant Medical Foundation
state: Maharashtra
city: Kolkata
country: India
facility: Medica Superspecialty Hospital
state: West Bengal
city: New Delhi
country: India
facility: Aakash Healthcare Super Speciality Hospital
city: Roma
country: Italy
facility: INMI Lazzaro Spallanzani
state: Rome
city: Milano
country: Italy
facility: Ospedale Niguarda Ca Granda
city: Prato
country: Italy
facility: Nuovo Ospedale di Prato S. Stefano
city: Yokohama
country: Japan
facility: Yokohama Municipal Citizen's Hospital
state: Kanagawa
city: Edagawa
country: Japan
facility: Edogawa Medicare Hospital
state: Tokyo
city: Hachioji
country: Japan
facility: Tokyo Medical University Hachioji Medical Center
state: Tokyo
city: Ansan-si
country: Korea, Republic of
facility: Korea University Ansan Hospital
state: Gyeonggi-do
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Boramae Medical Center
state: Seoul, Korea
city: Seoul
country: Korea, Republic of
facility: Seoul Medical Center
city: Mexico
country: Mexico
facility: Instituto Nacional de Cardiologia Ignacio Chavez
state: DF
city: Mexico
country: Mexico
facility: Instituto Nacional de Enfermedades Respiratorias
state: DF
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cancerologia
state: FD
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutrici Salva Zubir
state: Federal District
city: Yucatan
country: Mexico
facility: Hospital General Agustín O'Horán
state: Merida
city: Monterrey
country: Mexico
facility: ITESM Campus Monterrey
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
state: Nuevo León
city: Bayamon
country: Puerto Rico
facility: Advanced Clinical Research, LLC
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #15 named after O.M. Filatov
city: Moscow
country: Russian Federation
facility: First Moscow State Medical University n.a. Sechenov
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg City Pokrovskaya Hospital
city: Vitoria
country: Spain
facility: Hospital Txagorritxu
state: Alava
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor-INTERNAL MED
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Truro
country: United Kingdom
facility: The Royal Cornwall Hospital
state: Cornwall
city: Barnet
country: United Kingdom
facility: Barnet Hospital
state: Herts
city: London
country: United Kingdom
facility: St. George's University Hospitals NHS Foundation Trust
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-265-4559 or 1-317-615-4559) Mon - Fri 9AM - 5PM Eastern Time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Kramer A, Prinz C, Fichtner F, Fischer AL, Thieme V, Grundeis F, Spagl M, Seeber C, Piechotta V, Metzendorf MI, Golinski M, Moerer O, Stephani C, Mikolajewska A, Kluge S, Stegemann M, Laudi S, Skoetz N. Janus kinase inhibitors for the treatment of COVID-19. Cochrane Database Syst Rev. 2022 Jun 13;6(6):CD015209. doi: 10.1002/14651858.CD015209.
citation: Ely EW, Ramanan AV, Kartman CE, de Bono S, Liao R, Piruzeli MLB, Goldman JD, Saraiva JFK, Chakladar S, Marconi VC; COV-BARRIER Study Group. Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial. Lancet Respir Med. 2022 Apr;10(4):327-336. doi: 10.1016/S2213-2600(22)00006-6. Epub 2022 Feb 3.
citation: Marconi VC, Ramanan AV, de Bono S, Kartman CE, Krishnan V, Liao R, Piruzeli MLB, Goldman JD, Alatorre-Alexander J, de Cassia Pellegrini R, Estrada V, Som M, Cardoso A, Chakladar S, Crowe B, Reis P, Zhang X, Adams DH, Ely EW; COV-BARRIER Study Group. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med. 2021 Dec;9(12):1407-1418. doi: 10.1016/S2213-2600(21)00331-3. Epub 2021 Sep 1.