Oral Favipiravir Compared to Placebo in Subjects With Mild COVID-19

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy of oral favipiravir plus standard of care treatment (SOC) compared with placebo plus SOC in reducing the duration of shedding of SARS-CoV2 virus in patients with mild or asymptomatic COVID-19.

Official Title
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A Phase 2 Randomized, Double Blinded, Placebo Controlled Study of Oral Favipiravir Compared to Standard Supportive Care in Subjects With Mild or Asymptomatic COVID-19

Conditions
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Sars-CoV2, COVID-19

Intervention / Treatment
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* Drug: Favipiravir
* Drug: Placebo
* Other: Standard of care treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of COVID-19 disease: If symptomatic, presence of mild to moderate symptoms without signs of respiratory distress, with positive for SARS-CoV-2 diagnostic assay within 72 hours prior to.informed consent. If asymptomatic, initial diagnosis obtained no more than 72 hours prior to informed consent Subject agrees to maintain home or other quarantine as recommended by the study physician, except to visit the study site as required by the protocol Members of the same household may participate in the study as long as the inclusion and exclusion criteria are met Males must be sterile, OR agree not to donate semen AND agree to strictly adhere to contraceptive measures during the study and for seven days following the last dose of study medication Females must be unable to bear children, OR ensure that their male partner is incapable of fathering a child, OR, if of childbearing potential will strictly adhere to contraceptive measures during the study and for seven days following the last dose of study medication Females must agree to stop breast-feeding prior to first dose of study drug and through seven days after completing therapy Females must have a negative pregnancy test at screening Participant agrees to maintain home or other quarantine as recommended by the study physician, except to visit the study site as required by the protocol Exclusion Criteria: Concomitant bacterial respiratory infection documented by respiratory culture. NOTE: Subjects on empirical antibiotic treatment for possible but unproven bacterial pneumonia, but who are positive for SARS-CoV-2, are allowed in the study (will be randomized to the same treatment to maintain blinding). History of abnormal uric acid metabolism. History of hypersensitivity to an anti-viral nucleoside-analog drug targeting a viral RNA polymerase. Abnormal laboratory test results at screening: Use of adrenocorticosteroids (except topical or inhaled preparations or oral preparations equivalent to or less than 10 mg of oral prednisone) or immunosuppressive or immunomodulatory drugs (e.g., immunosuppressants, anticancer drugs, interleukins, interleukin antagonists or interleukin receptor blockers). NOTE: Treatment of study participants following institutional COVID-19 treatment policies or guidelines, including the use of immunomodulatory medications, is permitted. This excludes treatment with agents that have the potential for direct antiviral activity, including convalescent plasma and NO, and co-enrollment into other clinical studies that evaluate investigational agents for COVID-19. Serious chronic disease (e.g., human immunodeficiency virus [HIV], cancer requiring chemotherapy within the preceding 6 months, and/or moderate or severe hepatic insufficiency). Previously received favipiravir within the past 30 days. Advanced kidney disease Advanced liver disease History of alcohol or drug abuse in the previous two years. Psychiatric illness that is not well controlled (defined as stable on a regimen for more than one year). Taken another investigational drug within the past 30 days. Seemed by the Investigator to be ineligible for any reason.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Favipiravir<br>In addition to SOC, participants will receive favipiravir for 10 days, and be evaluated for health outcomes through day 28. | Drug: Favipiravir<br>* Favipiravir administered orally, 1800 mg on the first dose (day 1) followed by 800 mg twice daily for the next 9 days (days 2-10).<br>Other: Standard of care treatment<br>* Standard of care treatment for COVID-19 infection<br>|
| Active Comparator: Placebo<br>In addition to SOC, participants will receive placebo to match favipiravir for 10 days, and be evaluated for health outcomes through day 28. | Drug: Placebo<br>* Placebo to match favipiravir administered orally through day 10.<br>Other: Standard of care treatment<br>* Standard of care treatment for COVID-19 infection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Until Cessation of Oral Shedding of SARS-CoV-2 Virus | Time in days from randomization to the first two negative results of nasal and/or oropharyngeal swab. | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sars-CoV-2 Viral Load | Viral load (nucleic acid) will be assessed by RT-PCR Ct over time. Cycle threshold (Ct) denotes how many PCR cycles are required before the SARS-CoV-2 viral RNA reached a detectable level. Higher Ct values correspond to lower viral copy numbers. For reference, Ct values of 20 correspond to  2.12 x 106 viral copies per milliliter, while a Ct value of 40 is undetectable and is considered the lower limit of detection of this RT-PCR test for SARS-CoV-2. | Up to 28 days | 
| Count of Participants With Clinical Worsening of COVID-19 Disease | Clinical worsening is reported as the number of participants with hospitalization or emergency department (ED) visits. | Up to 28 days | 
| Count of Participants With Development of SARS-CoV-2 Antibodies |  | Up to 28 days | 
| Time Until Cessation of Symptoms | Time until cessation of symptoms is reported as days until initial resolution and sustained resolution of symptoms. | Up to 28 days | 
| Count of Participant With Absence of Development of Any Symptoms | This outcome will be assessed in patient who are asymptomatic of COVID-19 infection at the time of enrollment | Up to 28 days | 
| Cmax of Favipiravir | Cmax is a pharmacokinetic parameter that measures the maximum concentration of drug in plasma. | Days 1 and 10 (samples taken 30 minutes prior to and 1 hour following favipiravir administration) | 
| Cmin of Favipiravir | Cmin is a pharmacokinetic parameter that measures the minimum concentration of drug in plasma. | Days 1 and 10 (samples taken 30 minutes prior to and 1 hour following favipiravir administration) |