Baricitinib, Placebo and Antiviral Therapy for the Treatment of Patients With Moderate and Severe COVID-19

NCT04373044 | Terminated Phase 2 DMC FDA Drug

• 3 other identifiers: 0S-20-3NCI-2020-02685P30CA014089
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Symptomatic COVID-19 Infection Laboratory-Confirmed

Outcome Measures

Primary Outcomes (1)

• Proportion of patients requiring invasive mechanical ventilation or dying

  Descriptive statistics, including means, standard deviations, and ranges for continuous variables, as well as percentages and frequencies for categorical variables, will be provided to describe all the clinical findings in a cohort of symptomatic coronavirus disease 2019 (COVID-19)-infected subjects. The collected data will also be graphically presented in boxplots, histograms, and scatter plots. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity, will be made. Group comparisons will be made using either the parametric tests such as t-test and analysis of variance (ANOVA), or the non-parametric statistical method such as Wilcoxon and Kruskal-Wallis tests for continuous variable and Chi-square test for categorical variables. Point estimates, along with the corresponding p-values and 95% confidence intervals will be reported.

  Up to 14 days

Secondary Outcomes (13)

• Identification of clinical features (vitals signs - body temperature)

  Up to 28 days

• Identification of clinical features (vital signs - respiratory rate)

  Up to 28 days

• Identification of clinical features (vital signs - heart rate)

  Up to 28 days

• Identification of clinical features (vital signs - blood pressure)

  Up to 28 days

• Identification of clinical features (Imaging)

  Up to 28 days

Other Outcomes (1)

• Measurement of COVID19 viral burden

  Up to 14 days

Study Arms (2)

Arm II (placebo, antiviral therapy)

PLACEBO COMPARATOR

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.

Drug: Hydroxychloroquine; Drug: Placebo Administration

Treatment (baricitinib, antiviral therapy)

EXPERIMENTAL

Patients receive baricitinib PO daily, and standard of care hydroxychloroquine PO TID. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Drug: Baricitinib; Drug: Hydroxychloroquine

Interventions

Baricitinib DRUG

Given PO

Also known as: INCB 028050, INCB028050, LY 3009104, LY3009104

Treatment (baricitinib, antiviral therapy)

Hydroxychloroquine DRUG

Given PO

Arm II (placebo, antiviral therapy); Treatment (baricitinib, antiviral therapy)

Placebo Administration DRUG

Given Po

Arm II (placebo, antiviral therapy)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Interventions

baricitinib; Hydroxychloroquine

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Heinz-Josef Lenz, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: May 4, 2020
• Study Start: May 1, 2020
• Primary Completion: May 12, 2021
• Study Completion: May 12, 2021
• Last Updated: May 26, 2021

Record last verified: 2021-05

Locations

US (2)