Symptomatic COVID-19 Infection Laboratory-ConfirmedPhase 2NCT04373044
Baricitinib, Placebo and Antiviral Therapy for the Treatment of Patients With Moderate and Severe COVID-19
A Phase 2 study testing Baricitinib and Hydroxychloroquine in people with Symptomatic COVID-19 Infection Laboratory-Confirmed, run by University of Southern California at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Symptomatic COVID-19 Infection Laboratory-Confirmed
- What is being tested?
- Baricitinib and Hydroxychloroquine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 May 2020to 12 May 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Los Angeles County-USC Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
About this study
Official title: A Phase II Randomized Double-Blind Trial of Baricitinib or Placebo Combined With Antiviral Therapy in Patients With Moderate and Severe COVID-19
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
- Being tested
- Baricitinib, Hydroxychloroquine, Placebo Administration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BaricitinibDrug
Also called INCB 028050, INCB028050, LY 3009104, LY3009104
Given PO
Given PO
Placebo AdministrationDrug
Given Po
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Baricitinib; Drug: Hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 14 days
Secondary outcomes (13)
Identification of clinical features (vitals signs - body temperature)
Body temperature will be measured in degrees Fahrenheit using an automated thermometer.
Measured: Up to 28 days
Identification of clinical features (vital signs - respiratory rate)
Respiratory rate in times/minute
Measured: Up to 28 days
Identification of clinical features (vital signs - heart rate)
Heart rate in beats/minute
Measured: Up to 28 days
Identification of clinical features (vital signs - blood pressure)
Blood pressure in mmHg
Measured: Up to 28 days
Identification of clinical features (Imaging)
Chest X-ray or pulmonary computed tomography (CT) will be performed
Measured: Up to 28 days
Identification of clinical features (Lab - White Blood Count)
Assessment via standard blood chemistry and metabolic panel
Measured: Up to 28 days
Identification of clinical features (Lab - Absolute Lymphocyte Count)
Assessment via standard blood chemistry and metabolic panel
Measured: Up to 28 days
Identification of clinical features (Lab - Hemoglobin)
Assessment via standard blood chemistry and metabolic panel
Measured: Up to 28 days
Identification of clinical features (Lab - Creatinine)
Assessment via standard blood chemistry and metabolic panel
Measured: Up to 28 days
Identification of biomarkers (C-reactive protein)
CRP is assessed by routinely used determination of CRP.
Measured: Up to 14 days
Identification of biomarkers (Interleukin-6)
IL-6 levels will be assessed using commercial ELISA method
Measured: Up to 14 days
Identification of biomarkers (Tumor Necrosis Factor-alpha)
Tumor Necrosis Factor-alpha as measured in hospital laboratory
Measured: Up to 14 days
Identification of adverse events
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 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 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.
Measured: Up to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2020
- Study start1 May 2020
- Primary completion12 May 2021
- Study completion12 May 2021
Why it stopped: The study was terminated after the release of results of ACTT-2 (NCT04401579).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Symptomatic COVID-19 Infection Laboratory-ConfirmedStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Heinz-Josef Lenz, MD, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04373044
- Sponsor's protocol ID
- 0S-20-3
- Other IDs
- NCI-2020-02685, 0S-20-3, P30CA014089
- Status last verified
- May 2021
- First submitted
- 17 Apr 2020
- Last updated
- 26 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized Double-Blind Trial of Baricitinib or Placebo Combined With Antiviral Therapy in Patients With Moderate and Severe COVID-19
- ClinicalTrials.gov ID
- NCT04373044
- Acronym / sponsor ID
- 0S-20-3
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated after the release of results of ACTT-2 (NCT04401579).
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 1 May 2020 (actual)
- Primary completion
- 12 May 2021 (actual)
- Study completion
- 12 May 2021 (actual)
- First posted
- 4 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm II (placebo, antiviral therapy) | Placebo comparator | Drug: Hydroxychloroquine, Drug: Placebo AdministrationPatients 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. |
| Treatment (baricitinib, antiviral therapy) | Experimental | Drug: Baricitinib, Drug: HydroxychloroquinePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BaricitinibAlso: INCB 028050, INCB028050, LY 3009104, LY3009104Given PO | Drug | Treatment (baricitinib, antiviral therapy) |
| HydroxychloroquineGiven PO | Drug | Arm II (placebo, antiviral therapy), Treatment (baricitinib, antiviral therapy) |
| Placebo AdministrationGiven Po | Drug | Arm II (placebo, antiviral therapy) |
Primary outcome
Proportion of patients requiring invasive mechanical ventilation or dying
Time frame: Up to 14 days
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.
13 secondary outcomes
Identification of clinical features (vitals signs - body temperature)
Time frame: Up to 28 days
Identification of clinical features (vital signs - respiratory rate)
Time frame: Up to 28 days
Identification of clinical features (vital signs - heart rate)
Time frame: Up to 28 days
Identification of clinical features (vital signs - blood pressure)
Time frame: Up to 28 days
Identification of clinical features (Imaging)
Time frame: Up to 28 days
Identification of clinical features (Lab - White Blood Count)
Time frame: Up to 28 days
Identification of clinical features (Lab - Absolute Lymphocyte Count)
Time frame: Up to 28 days
Identification of clinical features (Lab - Hemoglobin)
Time frame: Up to 28 days
Identification of clinical features (Lab - Creatinine)
Time frame: Up to 28 days
Identification of biomarkers (C-reactive protein)
Time frame: Up to 14 days
Identification of biomarkers (Interleukin-6)
Time frame: Up to 14 days
Identification of biomarkers (Tumor Necrosis Factor-alpha)
Time frame: Up to 14 days
Identification of adverse events
Time frame: Up to 14 days
Results and safety
The study was stopped early (reason given: The study was terminated after the release of results of ACTT-2 (NCT04401579).). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heinz-Josef Lenz, MD principal investigator
University of Southern California
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Baricitinib and Hydroxychloroquine in people with Symptomatic COVID-19 Infection Laboratory-Confirmed, run by University of Southern California at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was terminated after the release of results of ACTT-2 (NCT04401579).). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients requiring invasive mechanical ventilation or dying (time frame: Up to 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2021.