Leflunomide in Mild COVID-19 Patients

Leflunomide for the Treatment of Ambulatory Patients With Mild COVID-19

This study aims to examine the tolerability of high dose of leflunomide in patients with COVID-19 who are being managed in the outpatient setting.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Leflunomide

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 mild COVID-19 symptoms. 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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Michael Millis, MD; Phone Number: 773 702 6319; Email: mmillis@surgery.bsd.uchicago.edu
• Study Contact Backup: Name: Laurencia Perea; Email: lperea@surgery.bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of high dose leflunomide as measured by leflunomide dose modifications	Number of subjects requiring leflunomide dose modifications	14 days
Tolerability of high dose leflunomide as measured by discontinuation of leflunomide	Number of subjects that discontinue leflunomide	14 days
Tolerability of high dose leflunomide as measured by Adverse Events	Number of Adverse Events observed in all subjects for the duration of the study	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to defervescence as measured in days while on treatment protocol	The number of days to reach first fever normalization (criteria for normalization: temperature < 100.4 F)	14 days
Resolution of other COVID-19 symptoms measured in days while on treatment protocol	Number of days to resolve other symptoms, as assessed by a standardized questionnaire for symptom assessment	14 days

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Michael Millis, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2020
• Primary Completion (Actual): January 31, 2022
• Study Completion (Actual): January 31, 2022

Study Registration Dates

• First Submitted: April 22, 2020
• First Submitted That Met QC Criteria: April 22, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: leflunomide
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Leflunomide
• Other Study ID Numbers: IRB20-0622

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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