Leflunomide in Mild COVID-19 Patients

• Sponsor: University of Chicago (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04361214
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 8.9
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

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.

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 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 Design

• Study Type: Interventional
• Anticipated 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
• Anticipated Primary Completion Date: Feb 1, 2021
• Anticipated Study Completion Date: Feb 1, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Tolerability of high dose leflunomide as measured by leflunomide dose modifications [14 days]

   Number of subjects requiring leflunomide dose modifications

2. Tolerability of high dose leflunomide as measured by discontinuation of leflunomide [14 days]

   Number of subjects that discontinue leflunomide

3. Tolerability of high dose leflunomide as measured by Adverse Events [14 days]

   Number of Adverse Events observed in all subjects for the duration of the study

Secondary Outcome Measures

1. Time to defervescence as measured in days while on treatment protocol [14 days]

   The number of days to reach first fever normalization (criteria for normalization: temperature < 100.4 F)

2. Resolution of other COVID-19 symptoms measured in days while on treatment protocol [14 days]

   Number of days to resolve other symptoms, as assessed by a standardized questionnaire for symptom assessment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• 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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT04361214
• Other Study ID Numbers: IRB20-0622
• First Posted: Apr 24, 2020
• Last Update Posted: Oct 29, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: leflunomide
• Additional relevant MeSH terms: COVID-19; Leflunomide

Study Results

No Results Posted as of Oct 29, 2020