Clinical trial NCT04340232: Safety and Efficacy of Baricitinib for COVID-19
Official title: Safety and Efficacy of Baricitinib for COVID-19
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: COVID-19
Keywords: JAK inhibitor
SARS-CoV-2
inflammation
cytokine release syndrome
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2020-04-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: This is an adaptive Phase 2/3 clinical trial, with a focus on the assessment of safety in the first 20 participants (Phase 2), followed by a much broader assessment of efficacy, while continuing to monitor safety, in an additional 60 participants (Phase 3, total participants across Phase 2/3 n=80). Both phases are single arm, open label, and occur at a single site at the University of Colorado Hospital (UCH). Data from participants in this study will be compared with data from other COVID-19 patients not receiving baricitinib. Study participants will receive 2 mg/day of baricitinib for 14 days and will be followed for up to 29 days.

Eligibility criteria: Inclusion Criteria:

* 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:

  1. Evidence of pneumonia, including radiographic infiltrates by imaging (chest x-ray, CT scan, etc.) or clinical assessment (rales/crackles on exam)
  2. 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

Exclusion Criteria:

* 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

Additional Exclusion Criteria for Phase 2 only:

• Invasive oxygen supplementation, including mechanical ventilation and extracorporeal membrane oxygenation (ECMO)

Primary outcomes:
measure: Phase 2: Cumulative incidence of Grade 3 and 4 adverse events (AEs)
timeFrame: Day 0 (screening) through Day 29
measure: Phase 2: Cumulative incidence of serious adverse events (SAEs)
timeFrame: Day 0 (screening) through Day 29
measure: Phase 2: Changes in white blood cell count (CBC) through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 2: Changes in hemoglobin through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 2: Changes in platelets through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 2: Changes in creatinine through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 2: Changes in glucose through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 2: Changes in prothrombin time (PT) through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 2: Changes in total bilirubin through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 2: Changes in ALT through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 2: Changes in AST through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 2: Changes in white blood cell count (CBC) through End of Study (EOS)
timeFrame: Day through Day 29 or hospital discharge, whichever is first
measure: Phase 2: Changes in hemoglobin through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 2: Changes in platelets through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 2: Changes in creatinine through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 2: Changes in glucose through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 2: Changes in prothrombin time (PT) though End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 2: Changes in total bilirubin through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 2: Changes in ALT through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 2: Changes in AST through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Percentage of patients reporting each severity on an 8-point ordinal scale at Day 15
timeFrame: Day 15
Secondary outcomes:
measure: Phase 2: Change in the 8-point ordinal scale
timeFrame: Day 1 to Day 29
measure: Phase 2: Change in National Early Warning Score (NEWS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Change in the 8-point ordinal scale
timeFrame: Day 1 to Day 29
measure: Phase 3: Change in National Early Warning Score (NEWS)
timeFrame: Day 1 to Day 29 or hospital discharge, whichever is first
measure: Phase 3: Time to an improvement of one category using the 8-point ordinal scale
timeFrame: Day 1 to Day 29 or hospital discharge, whichever is first
measure: Phase 3: Time to an improvement of two categories using the 8-point ordinal scale
timeFrame: Day 1 to Day 29 or hospital discharge, whichever is first
measure: Phase 3: Time to discharge or to a NEWS ≤2 and maintained for 24 hours, whichever occurs first
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Cumulative incidence of Grade 3 and 4 adverse events (AEs)
timeFrame: Day 0 (screening) through Day 29
measure: Phase 3: Cumulative incidence of serious adverse events (SAEs)
timeFrame: Day 0 (screening) through Day 29
measure: Phase 3: Duration of hospitalization
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Duration of new oxygen use
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Duration of new ventilator or ECMO use
timeFrame: Day 1 to Day 29 or hospital discharge, whichever is first
measure: Phase 3: Incidence of discontinuation or temporary suspension of drug for any reason
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Incidence of new oxygen use
timeFrame: Day 1 to Day 29 or hospital discharge, whichever is first
measure: Phase 3: Incidence of new ventilator use
timeFrame: Day 1 to Day 29 or hospital discharge, whichever is first
measure: Phase 3: Number of oxygen free days
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Number of ventilator or ECMO free days
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: 14 day mortality rate
timeFrame: Day 1 through Day 15
measure: Phase 3: 28 day mortality rate
timeFrame: Day 1 through Day 29
measure: Phase 3: Changes in white blood cell count (CBC) through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 3: Changes in hemoglobin through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 3: Changes in platelets through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 3: Changes in creatinine through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 3: Changes in glucose through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 3: Changes in prothrombin time (PT) through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 3: Changes in total bilirubin through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 3: Changes in ALT through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 3: Changes in AST through Day 15
timeFrame: Day 1 to Day 15
measure: Phase 3: Changes in white blood cell count (CBC) through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Changes in hemoglobin through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Changes in platelets through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Changes in creatinine through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Changes in glucose through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Changes in prothrombin time (PT) though End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Changes in total bilirubin through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Changes in ALT through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
measure: Phase 3: Changes in AST through End of Study (EOS)
timeFrame: Day 1 through Day 29 or hospital discharge, whichever is first
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Joaquin Espinosa, PhD
role: PRINCIPAL_INVESTIGATOR
References: