Randomized Multicenter Study on the Efficacy and Safety of Favipiravir for Parenteral Administration Compared to Standard of Care in Hospitalized Patients With COVID-19

Upon signing the informed consent form and screening, 217 eligible patients hospitalized with COVID-19 pneumonia were randomized at a 1:1 ratio to receive either Favipiravir intravenously by drip infusion for 2 hours 1600 mg twice a day (BID) on Day 1 followed by 800 mg BID on Days 2-14 (1600/800 mg), or SOC. The course of treatment by Favipiravir is 10 days.

Inclusion criteria

• Availability of the Informed Consent Form of the Patient Information Leaflet (PIL) signed and dated by patient.
• Men and women aged 18 to 80 years inclusive at the time of signing the Informed Consent Form in PIL.
• Confirmed case of COVID-19 at the time of screening based on SARS-CoV-2 RNA test using nucleic acid amplification (NAA) method. It is acceptable to include a patient with a presumptive COVID-19 diagnosis prior to receiving the results of SARS-CoV-2 RNA test made at the screening stage.
• Hospital admission due to COVID-19.
• Moderate severity infection with SARS-CoV-2:

• Clinical signs:
• Mandatory: CT pattern typical of a viral lesion (lesion volume is minimal or moderate; CT 1-2).
• Additional (at least 1 of the following criteria):
• body temperature > 38 °C;
• RR > 22/min;
• shortness of breath on exertion;
• SpO2 < 95%;
• Serum CRP > 10 mg/L.
• Patient's consent to use reliable contraceptive methods throughout the study and within 1 month for women and 3 months for men after its completion. Reliable means of contraception are: sexual abstinence, use of condom in combination with spermicide.

For men (optional): Consent to avoid sexual contact with pregnant women for the duration of the study and for 3 months after its completion.

Women incapable of childbearing may also participate in the study (with past history of: hysterectomy, tubal ligation, infertility, menopause for more than 2 years), as well as men with infertility or a history of vasectomy.

Exclusion criteria

• Hypersensitivity to favipiravir, remdesivir and/or other components of the study drug.
• Impossibility of CT procedure (for example, gypsum dressing or metal structures in the field of imaging).
• History of vaccination against COVID-19.
• History of presumptive or confirmed COVID-19 case of moderate, severe and extremely severe course of the disease.
• Use of favipiravir or remdesivir within 10 days prior to screening.
• The need to use drugs from the list of prohibited therapy.
• Meeting the criteria for severe and extremely severe course of the disease.
• Need for treatment in the intensive care unit.
• Impaired liver function (AST and/or ALT ≥ 2 UNL and/or total bilirubin ≥ 1.5 UNL) at the time of screening.
• Renal impairment (GFR < 60 ml/min) at the time of screening.
• History of gout.
• Positive testing for HIV, syphilis, hepatitis B and/or C.
• Chronic heart failure FC III-IV according to New York Heart Association (NYHA) functional classification (see Appendix 2).
• Malignancies in the past medical history.
• Alcohol, pharmacological and/or drug addiction in the past medical history and/or at the time of screening.
• Schizophrenia, schizoaffective disorder, bipolar disorder, or other history of mental pathology or suspicion of their presence at the time of screening.
• Severe, decompensated or unstable somatic diseases (any disease or condition that threaten the patient's life or impair the patient's prognosis, and also make it impossible for him/her to participate in the clinical study).
• Any history data that the investigating physician believes could lead to complication in the interpretation of the study results or create an additional risk to the patient as a result of his/her participation in the study.
• Patient's unwillingness or inability to comply with procedures of the Study Protocol (in the opinion of physician investigator).
• Pregnant or nursing women or women planning pregnancy.
• Participation in another clinical study for 3 months prior to inclusion in the study.
• Other conditions that, according to the physician investigator, prevent the patient from being included in the study.