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Leflunomide in Mild COVID-19 Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04361214
Recruitment Status : Recruiting
First Posted : April 24, 2020
Last Update Posted : May 20, 2020
Information provided by (Responsible Party):
University of Chicago

Brief Summary:
This study aims to examine the tolerability of high dose of leflunomide in patients with COVID-19 who are not yet hospitalized, but have risk factors for disease progression and complications.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Leflunomide Phase 1

Detailed Description:

This is a single are and single-center tolerability study of high dose leflunomide therapy in outpatient adult participants with mild COVID-19. In vitro studies have shown antiviral effects of leflunomide against SARS CoV-2, but the clinical outcomes in the disease have been variable. Our hypothesis is that targeting high risk patients earlier in the disease course and with a higher dose regimen are both required to see improvement in disease outcome measures in COVID-19. This study aims to prove the tolerability of high dose leflunomide in this setting.

Patients are selected based on identification of risk factors associated with more severe disease outcomes. Investigators will enroll twenty patients and perform a detailed Tele-helath interview to ensure they meet eligibility criteria and provide informed consent. 100 mg leflunomide daily for three days followed by 30 mg day will be prescribed. The subjects will be required to monitor their temperatures twice daily and a daily telephone call with an investigatory will review symptoms of disease and potential side effects of the drug. Subjects can discontinue the drug after five days if they no longer have fever, or take the drug for up to ten days if required for fever resolution.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Leflunomide for the Treatment of Ambulatory Patients With Mild COVID-19
Actual Study Start Date : May 5, 2020
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Leflunomide

Arm Intervention/treatment
Experimental: Leflunomide

Leflunomide 300 mg once daily administered for three days followed by 30 mg once daily administered for two days or until fevers abate (maximum ten days of treatment allowed).

If patients report symptoms attributed to the medication, the dose will be administered at 50 mg once daily for the loading dose followed by 20 mg once daily.

Drug: Leflunomide
Tolerability study of leflunomide 100 mg administered once daily for 3 days followed by 30 mg administered once daily for the duration of 2 - 7 days.

Primary Outcome Measures :
  1. Tolerability of high dose leflunomide as measured by leflunomide dose modifications [ Time Frame: 14 days ]
    Number of subjects requiring leflunomide dose modifications

  2. Tolerability of high dose leflunomide as measured by discontinuation of leflunomide [ Time Frame: 14 days ]
    Number of subjects that discontinue leflunomide

  3. Tolerability of high dose leflunomide as measured by Adverse Events [ Time Frame: 14 days ]
    Number of Adverse Events observed in all subjects for the duration of the study

Secondary Outcome Measures :
  1. Rate of hospitalization due to COVID-19 as measured by number of patients hospitalized [ Time Frame: 14 days ]
    Number of patients admitted to hospital during study period

  2. Time to defervescence as measured in days while on treatment protocol [ Time Frame: 14 days ]
    The number of days to reach first fever normalization (criteria for normalization: temperature < 100.4 F)

  3. Resolution of other COVID-19 symptoms measured in days while on treatment protocol [ Time Frame: 14 days ]
    Number of days to resolve other symptoms, as assessed by a standardized questionnaire for symptom assessment

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Being tested positive for SARS-Cov-2 in outpatient setting in drive-thru, ED, or ambulatory clinics at the University of Chicago within 72 hours of enrollment.
  • Age >18
  • Mild COVID-19, defined as the presence of any symptom consistent with an upper respiratory tract infection, including dry cough, sore throat, nasal congestion, fatigue, myalgia, headaches
  • Subjects must meet all the above-mentioned criteria, in addition to at least one of the following criteria:
  • Age > 55
  • Pre-existing pulmonary disease: airway diseases (asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis), history of active or treated lung cancer, history of pneumectomy, interstitial lung diseases, pulmonary hypertension, sleep apnea.
  • Diabetes: uncontrolled or controlled diabetes
  • Hypertension: uncontrolled or controlled hypertension
  • Chronic kidney disease stage 1-3
  • History of cardiovascular disease: history of coronary artery disease (angina, unstable angina or myocardium infarction, history of percutaneous coronary intervention, history of coronary artery bypass graft) cerebrovascular disease (embolic and hemorrhagic strokes, transitory ischemic stroke), valvular heart disease (surgically corrected or not), peripheral artery disease, heart failure.
  • History of immunosuppression: solid organ or bone marrow transplant, use of immunosuppressive antimetabolic and biologic agents, intrinsic immunodeficiencies, HIV infection.
  • Active cancer diagnosis, on palliative treatment or requiring current therapy with antimetabolic agents, immunotherapy or radiotherapy.
  • At least one fever every 24 hours for > 72h

Exclusion Criteria:

  • Participation in any other clinical trial of an experimental agent treatment for COVID-19
  • Current hospitalization
  • Known hypersensitivity to leflunomide
  • Currently taking methotrexate
  • Currently taking terliflunomide
  • Known chronic kidney disease, stage 4-5, or receiving dialysis
  • History of liver disease
  • History of interstitial lung disease
  • Pregnancy and lactation - pregnancy test required for females
  • Inability to monitor body temperature (oral, axillary, tympanic or frontal) at least twice a day from study enrollment day (Day 1) to the end of the study (Day 14).
  • Inability to provide informed consent to the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04361214

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Contact: Michael Millis, MD 773 702 6319
Contact: Laurencia Perea

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United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Michael Millis   
Sponsors and Collaborators
University of Chicago
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Principal Investigator: Michael Millis, MD University of Chicago
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Responsible Party: University of Chicago Identifier: NCT04361214    
Other Study ID Numbers: IRB20-0622
First Posted: April 24, 2020    Key Record Dates
Last Update Posted: May 20, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by University of Chicago:
Additional relevant MeSH terms:
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Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs