Safety and Efficacy of Baricitinib for COVID-19

NCT04340232 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 20-0738
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study plans to learn more about the effects of a medicine called baricitinib on the progression of COVID-19 (coronavirus disease of 2019), the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Baricitinib is FDA-approved for the treatment of rheumatoid arthritis, an autoimmune condition. This study intends to define the impact of baricitinib on the severity and progression of COVID-19. This drug might to lower the hyperinflammation caused by the virus, which would prevent damage to the lungs and possibly other organs. The study will recruit patients who have been diagnosed with COVID-19. The goal is to recruit 80 patients.

Conditions

COVID-19

Keywords

JAK inhibitor; SARS-CoV-2; inflammation; cytokine release syndrome

Outcome Measures

Primary Outcomes (21)

• Phase 2: Cumulative incidence of Grade 3 and 4 adverse events (AEs)

  Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening. AEs will be collected and graded daily and cumulative incidence will be reported.

  Day 0 (screening) through Day 29

• Phase 2: Cumulative incidence of serious adverse events (SAEs)

  Description: An SAE is defined as an AE that is life-threatening or results in death, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. SAEs will be collected and graded daily and cumulative incidence will be reported.

  Day 0 (screening) through Day 29

• Phase 2: Changes in white blood cell count (CBC) through Day 15

  Safety assessment via standard blood chemistry and metabolic panels will be performed daily as recommended by participant's physician as standard of care (SOC). Mean changes from baseline to Day 15 will be reported.

  Day 1 to Day 15

• Phase 2: Changes in hemoglobin through Day 15

  Day 1 to Day 15

• Phase 2: Changes in platelets through Day 15

  Day 1 to Day 15

• Phase 2: Changes in creatinine through Day 15

  Day 1 to Day 15

• Phase 2: Changes in glucose through Day 15

  Day 1 to Day 15

• Phase 2: Changes in prothrombin time (PT) through Day 15

  Day 1 to Day 15

• Phase 2: Changes in total bilirubin through Day 15

  Day 1 to Day 15

• Phase 2: Changes in ALT through Day 15

  Day 1 to Day 15

• Phase 2: Changes in AST through Day 15

  Day 1 to Day 15

• Phase 2: Changes in white blood cell count (CBC) through End of Study (EOS)

  Safety assessment via standard blood chemistry and metabolic panels will be performed daily as recommended by participant's physician as SOC. Mean changes from baseline to EOS will be reported.

  Day through Day 29 or hospital discharge, whichever is first

• Phase 2: Changes in hemoglobin through End of Study (EOS)

  Day 1 through Day 29 or hospital discharge, whichever is first

• Phase 2: Changes in platelets through End of Study (EOS)

  Day 1 through Day 29 or hospital discharge, whichever is first

• Phase 2: Changes in creatinine through End of Study (EOS)

  Day 1 through Day 29 or hospital discharge, whichever is first

• Phase 2: Changes in glucose through End of Study (EOS)

  Day 1 through Day 29 or hospital discharge, whichever is first

• Phase 2: Changes in prothrombin time (PT) though End of Study (EOS)

  Day 1 through Day 29 or hospital discharge, whichever is first

• Phase 2: Changes in total bilirubin through End of Study (EOS)

  Day 1 through Day 29 or hospital discharge, whichever is first

• Phase 2: Changes in ALT through End of Study (EOS)

  Day 1 through Day 29 or hospital discharge, whichever is first

• Phase 2: Changes in AST through End of Study (EOS)

  Day 1 through Day 29 or hospital discharge, whichever is first

• Phase 3: Percentage of patients reporting each severity on an 8-point ordinal scale at Day 15

  The 8-point ordinal scale described below, where a lower score indicates a worse outcome, will be performed daily or as recommended by participant's physician as SOC. The percent of participants scored at each severity will be reported on Day 15. The 8-point ordinal scale is as follows: 1. Death 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) 6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care 7. Not hospitalized, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities

  Day 15

Secondary Outcomes (37)

• Phase 2: Change in the 8-point ordinal scale

  Day 1 to Day 29

• Phase 2: Change in National Early Warning Score (NEWS)

  Day 1 through Day 29 or hospital discharge, whichever is first

• Phase 3: Change in the 8-point ordinal scale

  Day 1 to Day 29

• Phase 3: Change in National Early Warning Score (NEWS)

  Day 1 to Day 29 or hospital discharge, whichever is first

• Phase 3: Time to an improvement of one category using the 8-point ordinal scale

  Day 1 to Day 29 or hospital discharge, whichever is first

Study Arms (1)

Baricitinib Arm

EXPERIMENTAL

This study is an Adaptive Phase 2/3 trial designed to test the safety (Phase 2) and efficacy (Phase 2 and 3) of baricitinib to treat COVID-19. Phase 2 consists of a single-arm, open-label assignment of 20 participants receiving 2 mg baricitinib once daily for 14 days. Phase 3 consists of a single-arm, open-label assignment of 60 additional participants receiving baricitinib at the same dose. In both phases, participants will be monitored daily while hospitalized for 29 days, or until discharge, whichever occurs first. Participants who are discharged will be followed up with via phone on Day 15 and Day 29.

Drug: Baricitinib

Interventions

Baricitinib DRUG

Subjects will receive a 2 mg oral dose of baricitinib.

Baricitinib Arm

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18 - 89 years at time of enrollment
• Hospitalized (or documented plan to hospitalize if patient is in the emergency department) with symptoms suggestive of COVID-19
• Illness of any duration that meets each of the following:
• Evidence of pneumonia, including radiographic infiltrates by imaging (chest x-ray, CT scan, etc.) or clinical assessment (rales/crackles on exam)
• Requires supportive care, including non-invasive supplemental oxygen
• Laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay within 7 days of enrollment
• Understands and agrees to comply with planned study procedures
• Provides informed consent signed by study patient or legally acceptable representative

You may not qualify if:

• Absolute lymphocyte count is less than 500 cells/mm
• Absolute neutrophil count is less than 1000 cells/mm
• Hemoglobin level is less than 8 g/dL
• Estimated GFR is less than 60 mL/min/1.73 m2
• ALT or AST is over 5 times the upper limit of normal
• Treatment with other JAK inhibitors, OAT3 inhibitors, biologic disease-modifying anti-rheumatic drugs (DMARDs), anti-IL-6 or anti-IL-6R antibodies, or potent immunosuppressants such as azathioprine. and cyclosporine concurrently or within the past 5 days. Note: recent or concurrent treatment with hydroxychloroquine or chloroquine is allowable, as these are 'non-biologic' DMARDs with potential antiviral activity.
• History of HIV infection and on active immunosuppressant therapy
• Current hematological or solid organ malignancy and on active immunosuppressant therapy
• Active tuberculosis (TB) infection or known or suspected systemic bacterial or fungal infection
• Pregnancy or breast feeding
• Known allergy to baricitinib
• In the opinion of the investigator, they are unlikely to survive for \>48 hours from screening
• Any physical examination findings and/or history of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study
• Invasive oxygen supplementation, including mechanical ventilation and extracorporeal membrane oxygenation (ECMO)

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado, Denver

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

COVID-19; Inflammation; Cytokine Release Syndrome

Interventions

baricitinib

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Systemic Inflammatory Response Syndrome; Shock

Study Officials

• Joaquin Espinosa, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single arm, open label, single site study. Data from participants in this study with data from other COVID-19 patients not receiving baricitinib.

Study Record Dates

• First Submitted: April 3, 2020
• First Posted: April 9, 2020
• Study Start: March 1, 2021
• Primary Completion: August 1, 2021
• Study Completion: October 1, 2021
• Last Updated: March 8, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Data will be made available upon publication in a peer-reviewed journal.
• Access Criteria: Data access requests will be reviewed by the sponsor-investigator and collaborators.

Locations

US (1)