This phase II trial studies the effect of baricitinib in combination with antiviral therapy for the treatment of patients with moderate or severe coronavirus disease-2019 (COVID-19). Treatment with antiviral medications such as hydroxychloroquine, lopinavir/ritonavir, and/or remdesivir may act against infection caused by the virus responsible for COVID-19. Baricitinib may reduce lung inflammation. Giving baricitinib in combination with antiviral therapy may reduce the risk of the disease from getting worse and may help prevent the need for being placed on a ventilator should the disease worsen compared to antiviral therapy alone.
PRIMARY OBJECTIVE:
I. To determine the efficacy of baricitinib combined with antiviral therapy in participants
with COVID-19-related moderate and severe disease in terms of reduction of the proportion of
participants requiring invasive mechanical ventilation or dying or requiring anti-IL6
monoclonal antibodies compared to that seen with antiviral alone within 60 days.
SECONDARY OBJECTIVES:
I. To describe the clinical findings in a cohort of symptomatic COVID-19-infected
participants.
II. To test whether cytokine signatures predict progression to invasive ventilatory support
or death.
III. To describe adverse events (AEs) associated with baricitinib when administered at 4mg in
combination with antivirals.
EXPLORATORY OBJECTIVES:
I. Describe the decay in quantitative viral burden from saliva samples collected sequentially
under treatment with baricitinib in combination with antivirals.
II. To obtain preliminary data on efficacy and tolerability of baricitinib in combination
with antivirals in participants with cancer.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients receive baricitinib orally (PO) daily, and standard of care
hydroxychloroquine PO three times daily (TID). Treatment continues for 14 days in the absence
of disease progression or unacceptable toxicity.
GROUP II: Patients receive placebo PO daily, and standard of care hydroxychloroquine PO TID.
Treatment continues for 14 days in the absence of disease progression or unacceptable
toxicity.
Patients are followed for 60 days after enrollment to treatment.
Drug: Baricitinib
Given PO
Other Name: Array
Drug: Hydroxychloroquine
Given PO
Drug: Placebo Administration
Given Po
Inclusion Criteria:
- Positive polymerase chain reaction (PCR) for severe acute respiratory syndrome
coronavirus 2 (SARS-CoV2) in a respiratory tract sample OR positive anti-SARS CoV2 IgM
antibody test that is approved by Food and Drug Administration (FDA) or allowed under
an emergency use authorization; either result obtained within 5 days prior to study
entry
- Cough and/or pneumonia on chest imaging
- Moderate disease with risk factor(s): Peripheral capillary oxygen saturation (SpO2) >=
92% on room air with one of the following risk factors for development of severe
disease: age >= 60 years, receiving medication for hypertension, diagnosed diabetes
mellitus, known cardiac disease, chronic lung disease, obesity (body mass index [BMI]
>= 35 kg/m^2), active malignancy, immunosuppression (receiving biologics or
glucocorticoids >= 20 mg/d prednisone equivalent for > 2 weeks)
- Severe disease: SpO2 =< 92% on room air
- Ability to understand and the willingness to sign a written informed consent. Adults
not competent to consent will be enrolled with the use of an appropriate legally
authorized representative (per California Code, Health and Safety Code - HSC)
- FDA regulations generally require that the informed consent of a participant be
documented by the use of a written consent form approved by the IRB and signed
and dated by the participant or the participant's legally authorized
representative at the time of consent (21 case form report [CFR] 50.27[a]). In
light of COVID-19 infection control measures, the following procedure would
satisfy documentation of this requirement if the participant signing the informed
consent is in COVID-19 isolation. If the technology is available, electronic
methods of obtaining informed consent will be taken. The electronic consent and
Health Insurance Portability and Accountability Act (HIPAA) forms will be
uploaded and available through REDCap
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 7 days following completion of therapy.
NOTE: Should a woman become pregnant or suspect she is pregnant while participating in
this study, she should inform her treating physician immediately. Women of
child-bearing potential should use highly effective methods of birth control. These
are those methods of contraception, alone or in combination, that result in a low
failure rate (i.e, less than 1% per year) when used consistently and correctly
Exclusion Criteria:
- Mechanical ventilation, high-flow nasal oxygen, biphasic positive airway pressure
(BiPAP)
- Venous thromboembolism within 12 weeks or previously diagnosed thrombophilic
conditions or conditions that increase the risk of thrombosis. Individuals with > 1
episode of venous thromboembolism or pulmonary embolism in the past will also be
excluded
- Prior receipt of other immunomodulatory drugs (e.g., any JAK inhibitors,
immunomodulatory biologics, or other immunomodulatory investigational products) within
14 days prior to enrollment
- Current treatment with probenecid
- Known infection with human immunodeficiency syndrome (HIV), or active infection with
hepatitis B or hepatitis C
- Participant with known active or latent tuberculosis infection
- Pregnancy and lactation
- Any serious acute infections or known active or latent tuberculosis
- All enrolled participants will be screened for latent tuberculosis infection by
testing QuantiFERON-TB Gold Plus, but a documented negative test will not be
required prior to entry. If a participant is found to have positive QuantiFERON
that results after enrollment, baricitinib will be discontinued
- Solid organ transplant recipient
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 x upper limit
of normal
- Absolute neutrophil count < 1000/mm^3
- Absolute lymphocyte count < 200/mm^3
- Hemoglobin < 8 g/dl
- Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m^2
- Any medical condition in the opinion of the investigator that would place the
participant at undue high risk for participation in the trial
- Hypersensitivity to the active substance or to any of the excipients
Los Angeles County-USC Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Heinz-Josef Lenz, MD, Principal Investigator
University of Southern California