Clinical Trial of Favipiravir Treatment of Patients With COVID-19

An Investigation of the Efficacy and Safety of Favipiravir in COVID-19 Patients With Mild Pneumonia - An Open-label Randomized Controlled Study -

To verify that the efficacy of favipiravir exceeds that of the actual supportive care (symptomatic therapy) in SARS-CoV-2 infected patients (COVID-19 patients) with mild pneumonia, using the time required to improve clinical symptoms as the primary endpoint.

Inclusion Criteria:

1. Age 18 to 74 years (at the time of informed consent)

2. Male or female

3. Patients who meet all of the following three criteria at the time of enrolment:

   1. SARS-CoV-2-positive patients as measured by rtPCR by nasopharyngeal sampling
   2. Moderate patients with radiological evidence of pneumonia in the lung at the time of enrolment (RTG, CT, or UH), clearly described by the radiologist following the imaging examination. (The diagnosis of the finding should clearly include the presence of pneumonia to any extent, localization, and extent)
   3. Body temperature 37,5°C or more
   4. Patient requires hospitalization during the treatment period (obligation to stay in the hospital for whole treatment period, 14 days)

4. For premenopausal females, patients who have been confirmed to be negative on a pregnancy test before administration of the study drug

5. Signed informed consent by the patient or by the legal representative -

Exclusion Criteria:

1. Body temperature of 37.5 °C or higher for more than 10 days after the onset of elevated body temperature

2. Patients with SpO2 less than 95%

3. Patient requires supportive oxygen therapy

4. Patients who show increased procalcitonin levels before the start of the study drug administration and are suspected to have concurrent bacterial infection

5. Patients with proven concomitant systematic fungal infection prior to initiation of study drug.

6. Patients with concurrent congestive heart failure (NYHA III-IV)

7. Patients with severe hepatic impairment equivalent to Grade C on Child-Pugh classification

8. Patient with renal impairment requiring dialysis.

9. Patients with disturbed consciousness such as disturbed orientation.

10. Pregnant or possibly pregnant patients.

11. Female patients who are woman of childbearing potential and unable to consent to the use of dual contraception from the start of favipiravir administration to 30 days after the end of favipiravir administration. Dual contraception is a combination of two of the following: Barrier method of contraception: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide; IUD; Hormone-based contraceptive; Tubal ligation

12. Male patients whose are unable to consent to the use of the barrier method of contraception (condom) from the start of favipiravir administration to 90 days after the end of favipiravir administration. Male patients who are planning to donate sperm from the start up until 90 days after the end of favipiravir administration.

13. Female patients who intend to breastfeed from the start of favipiravir administration until 14 days after discontinuation of favipiravir administration

14. Patients with herditary xanthinuria

15. Patients who have hyperuricemia (> 1 mg/dL) or xanthine urinary calculi

16. Patients with a history of gout or on treatment for gout or hyperuricemia

17. Patients receiving immunosuppressants

18. Patients who received interferon-alpha or drugs with reported antiviral activity against SARS-CoV-2 (hydroxychloroquine sulfate, chloroquine phosphate, lopinavir-ritonavir combination, ciclesonide, nafamostat mesylate, camostat mesylate, remdesivir, etc.) within 9 days after fever onset (37.5°C or more)

19. Patients in whom this episode of infection is a recurrence or a reinfection with the SARS-CoV-2 infection

20. Patients who have previously been treated with favipiravir (T-705a)

21. Other patients judged ineligible by the investigator, sub-investigator, or assigned physician.

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