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

A Multicenter, Open-Label, Pharmacokinetic and Safety Study of Baricitinib in Pediatric Patients From 1 Year to Less Than 18 Years Old Hospitalized With COVID-19

The purpose for this study is to determine if the study drug baricitinib is effective and safe in hospitalized pediatric participants with Coronavirus disease 2019 (COVID -19) and to confirm the dose.

Study Overview

• Status: Terminated
• Conditions: Covid19; Corona Virus Infection
• Intervention / Treatment: Drug: Baricitinib

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Campinas, Brazil, 13060-080
    • Instituto de Pesquisa clinica de Campinas
  • Campinas, Brazil, 13034-685
    • Centro de Pesquisa Sao Lucas
  • Jaú, Brazil, 17201130
    • CECIP - Centro de Estudos do Interior Paulista
  • Porto Alegre, Brazil, 90410000
    • Hospital de Clínicas de Porto Alegre
  • Santo André, Brazil, 09080-110
    • Pesquisare Saude
• Mexico
  • Mexico City, Mexico, 04530
    • Instituto Nacional de Pediatría
  • Mexico City, Mexico, 06720
    • Hospital Infantil de México Federico Gómez
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Pamplona, Spain, 31009
    • Complejo Hospitalario de Navarra
  • Vitoria-Gasteiz, Spain, 01009
    • Hospital Universitario de Araba (HUA)- Hospital Txagorritxu
• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • Arnold Palmer Hospital for Children
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hospitalized with coronavirus (SARS-CoV-2) infection.
• Male or female participants from 1 to <18 years of age.
• Requires supplemental oxygen and have chest imaging findings to confirm respiratory disease due to COVID-19 within 72 hours of study entry and enrollment.
• Supplemental oxygen including but not limited to: nasal cannula, mask, high flow devices, CPAP/BiPAP, invasive mechanical ventilation as well as ECMO.

Exclusion Criteria:

• Are receiving biologic treatments (such as Tumor Necrosis Factor [TNF] inhibitors, interleukin inhibitors, T-cell or B-cell targeted therapies, interferon, or Janus kinase (JAK) inhibitors); or are receiving other immunosuppressants such that, in the opinion of the investigator, participating in the study would put the participant at an unacceptable risk of immunosuppression.

Note: A washout period is required prior to screening.

• Are receiving strong inhibitors of Organic Anion Transporter 3 (OAT3) (such as probenecid) that cannot be discontinued at study entry.
• 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 non-live (inactivated) vaccinations are 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]) or considered high risk of 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 AAULN.
• Estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease [MDRD]) <40 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, in the opinion of the investigator or sponsor, at risk of immunosuppression or otherwise unsuitable for inclusion in 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Baricitinib QD; Participants received baricitinib as an oral suspension (2 milligrams per milliliter [mg/mL]) administered once daily (QD), with age group-based dosing: 4 milligrams (mg) for participants aged 10 to <18 years and up to 2 mg for those aged 1 to <10 years.; Treatment was administered for up to 14 days or until hospital discharge, whichever occurred first, with follow-up assessments through approximately Day 60.

Drug: Baricitinib; Given Orally; Other Names: LY3009104

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC) of Baricitinib	PK: Overall AUC of Baricitinib in pediatric participants with COVID-19. Summarized data were reported in this outcome measure.	Day 1: 0.25, 0.5, 2-4 hours post-dose; Day 4: Pre-dose, 1, 6-10 hours post-dose
PK: Maximum Concentration (Cmax) of Baricitinib	PK: Overall Cmax of Baricitinib in pediatric participants with COVID-19. Summarized data were reported in this outcome measure.	Day 1: 0.25, 0.5, 2-4 hours post-dose; Day 4: Pre-dose, 1, 6-10 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Progressed to Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO]) by Day 28	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. NIAID-OS (range: 1-8); minimum value: 1 (not hospitalized, no limitations on activities); maximum value: 8 (death); higher scores indicate worse clinical status. Progression to ventilation (only progressed excluding death) by Day 28 was defined as reaching NIAID-OS ≥6; for participants with baseline NIAID-OS 6, progression required NIAID-OS ≥7, and those with a baseline score of 7 were excluded.	Day 1 to Day 28
Percentage of Participants Who Died or Progressed to Non-Invasive Ventilation/High-Flow Oxygen, Invasive Mechanical Ventilation, or ECMO by Day 28	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. NIAID-OS (range: 1-8); minimum value: 1 (not hospitalized, no limitations on activities); maximum value: 8 (death); higher scores indicate worse clinical status. Progression to ventilation (who died or progressed) by Day 28, defined as reaching a score ≥6; for baseline scores of 6 and 7, progression required scores ≥7 and Death (NIAID-OS=8).	Day 1 to Day 28
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	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. NIAID-OS (range: 1-8); minimum value: 1 (not hospitalized, no limitations on activities); maximum value: 8 (death); higher scores indicate worse clinical status. At each visit (Day 4/7/10/14/28), percentage of participants with ≥1-point improvement on NIAID-OS or discharged alive by that visit were reported in this outcome measure.	Day 4, Day 7, Day 10, Day 14, and Day 28
Number of Ventilator-Free Days (Days Free of Invasive Mechanical Ventilation)	NIAID-OS is an assessment of clinical status. The 8-point scale 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. NIAID-OS (range: 1-8); minimum value: 1 (not hospitalized, no limitations on activities); maximum value: 8 (death); higher scores indicate worse clinical status. Number of ventilator free-days were defined as total number of days participants were alive and had NIAID-OS <7 point (free of invasive mechanical ventilation/ECMO) by Day 28.	Day 1 to Day 28
Time to Recovery	NIAID-OS is an assessment of clinical status. The 8-point scale 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. NIAID-OS (range: 1-8); minimum value: 1 (not hospitalized, no limitations on activities); maximum value: 8 (death); higher scores indicate worse clinical status. Time to recovery was time from Day 1 to the first day the participant's maximum daily NIAID-OS was 1, 2, or 3. Participants who died before recovery were censored at Day 28 (not considered recovered).	Day 1 to Day 28
Percentage of Participants With Overall Improvement in the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4	NIAID-OS is an assessment of clinical status. The 8-point 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. NIAID-OS (range: 1-8); minimum value: 1 (not hospitalized, no limitations on activities); maximum value: 8 (death); higher scores indicate worse clinical status. Improvement was defined as the reduction from baseline in the NIAID-OS score, calculated as baseline score minus Day 4 score. A higher positive value indicates greater improvement.	Day 4
Percentage of Participants With Overall Improvement in the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7	NIAID-OS is an assessment of clinical status. The 8-point 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. NIAID-OS (range: 1-8); minimum value: 1 (not hospitalized, no limitations on activities); maximum value: 8 (death); higher scores indicate worse clinical status. Improvement was defined as the reduction from baseline in the NIAID-OS score, calculated as baseline score minus Day 7 score. A higher positive value indicates greater improvement.	Day 7
Percentage of Participants With Overall Improvement in the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10	NIAID-OS is an assessment of clinical status. The 8-point 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. NIAID-OS (range: 1-8); minimum value: 1 (not hospitalized, no limitations on activities); maximum value: 8 (death); higher scores indicate worse clinical status. Improvement was defined as the reduction from baseline in the NIAID-OS score, calculated as baseline score minus Day 10 score. A higher positive value indicates greater improvement.	Day 10
Percentage of Participants With Overall Improvement in the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14	NIAID-OS is an assessment of clinical status. The 8-point 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. NIAID-OS (range: 1-8); minimum value: 1 (not hospitalized, no limitations on activities); maximum value: 8 (death); higher scores indicate worse clinical status. Improvement was defined as the reduction from baseline in the NIAID-OS score, calculated as baseline score minus Day 14 score. A higher positive value indicates greater improvement.	Day 14
Percentage of Participants With Overall Improvement in the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 28	NIAID-OS is an assessment of clinical status. The 8-point 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. NIAID-OS (range: 1-8); minimum value: 1 (not hospitalized, no limitations on activities); maximum value: 8 (death); higher scores indicate worse clinical status. Improvement was defined as the reduction from baseline in the NIAID-OS score, calculated as baseline score minus Day 28 score. A higher positive value indicates greater improvement.	Day 28
Duration of Hospitalization	NIAID-OS is an assessment of clinical status. The 8-point scale 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; 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. NIAID-OS (range:1-8); minimum value:1; maximum value:8; higher scores indicate worse clinical status. Duration of hospitalization through Day 28 was defined as the total number of days with NIAID-OS scores of 4, 5, 6, or 7. Participants who died on or before Day 28 were assigned 28 days. For Day 1, hospitalization status was determined using worst NIAID-OS value recorded between baseline and the remainder of Day 1.	Day 1 to Day 28
All-Cause Mortality	Number of deaths by day 60 were reported in this outcome measure.	Baseline (Day 1) up to end of follow-up (up to Day 60)
Duration of Stay in the Intensive Care Unit (ICU) in Days	Duration of ICU stay through Day 28 was defined as the total number of days spent in the ICU through Day 28, with days following death counted up to Day 28. For participants alive at Day 28, duration was calculated as (Date of ICU discharge - Date of ICU admission) + 1. For participants who died in the ICU on or before Day 28, duration was calculated as (Date of death - Date of ICU admission + 1) + (Date of Day 28 - Date of death).	Day 1 to Day 28

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2021
• Primary Completion (Actual): September 5, 2024
• Study Completion (Actual): November 4, 2024

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (Actual): October 12, 2021

Study Record Updates

• Last Update Posted (Actual): August 11, 2026
• Last Update Submitted That Met QC Criteria: July 18, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: coronavirus
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronaviridae Infections; Nidovirales Infections; COVID-19; Coronavirus Infections; baricitinib
• Other Study ID Numbers: 18253; I4V-MC-KHAB (Other Identifier: Eli Lilly and Company); 2021-001338-21 (EudraCT Number); 2024-516824-32-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No