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

Eli Lilly and Company96 sites in 3 countries1,525 target enrollmentJune 12, 2020

ConditionsCOVID-19

InterventionsBaricitinib Placebo

DrugsBaricitinib Placebo

Overview

Phase: Phase 3
Intervention: Baricitinib
Conditions: COVID-19
Sponsor: Eli Lilly and Company
Enrollment: 1525
Locations: 96
Primary Endpoint: Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO])
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

Registry

clinicaltrials.gov

Start Date

June 12, 2020

End Date

June 10, 2021

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Eli Lilly and Company

Responsible Party

Sponsor

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-
•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-
•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.

Arms & Interventions

Baricitinib + Standard of Care (SOC)

4 milligrams (mg) of baricitinib (given as two 2 mg tablets) administered orally every day (QD) with standard of care.

Intervention: Baricitinib

Placebo + SOC

Placebo (given as two placebo tablets) administered orally QD with standard of care.

Intervention: Placebo

Outcomes

Primary Outcomes

Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO])

Time Frame: 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

Time Frame: Day 1 to Day 28

Percentage of participants who die or require non-invasive ventilation or invasive mechanical ventilation, including ECMO.

Secondary Outcomes

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)
Number of Ventilator-Free Days(Day 1 to Day 28)
Time to Recovery(Day 1 to Day 28)
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)
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)
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)
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)
Duration of Hospitalization(Days 1 to Day 28)
Percentage of Participants With a Change in Oxygen Saturation From < 94% to ≥ 94% From Baseline(Day 10)
Overall Mortality(Day 1 to Day 28)
Duration of Stay in the Intensive Care Unit (ICU) in Days(Day 1 to Day 28)
Time to Clinical Deterioration (One-category Increase on the NIAID-OS)(Day 1 to Day 28)
Time to Resolution of Fever in Participants With Fever at Baseline(Day 1 to Day 28)
Time to Independence From Non-Invasive Mechanical Ventilation(Day 1 to Day 28)
Time to Independence From Oxygen Therapy in Days(Day 1 to Day 28)
Mean Change From Baseline on the National Early Warning Score (NEWS)(Baseline, Day 4; Baseline, Day 7; Baseline, Day 10; Baseline, Day 14)
Number of Days With Supplemental Oxygen Use(Day 1 to Day 28)
Number of Days of Resting Respiratory Rate <24 Breaths Per Minute(Day 1 to Day 28)
Time to Definitive Extubation(Day 1 to Day 28)