Study of Efficacy and Safety of TL-FVP-t vs. SOC in Patients With Mild to Moderate COVID-19

This was an open label, randomized, controlled, multicenter Phase 3 study of TL-FVP-t in outpatients and inpatients with mild to moderate COVID-19. After stratification by the severity of their disease (mild or moderate), age (18-44 or ≥ 45 years) and CT severity subjects were randomized at a rate of 2:1 to receive either TL-FVP-t + standard concomitant therapy or standard ethiptropic therapy (standard of care - SOC) including standard concomitant therapy. Standard ethiptropic therapy according to MoH of Russian Federation included umifenovir + intranasal recombinant interferon alpha, hydroxichloroquine, or chloroquine.

The dose regimen was the following: TL-FVP-t at a dose of 1800 mg BID on the Day 1 followed by 800 mg BID during the next 9 days. The study included the period of therapy (10 days) and follow-up period (18 days).

Inclusion criteria

• Informed consent form signed.
• Males and females aged 18-60 years;
• Diagnosis of coronavirus disease caused by SARS-CoV-2 (COVID-19) in a mild or moderate form (without respiratory failure).
• Duration of infection symptoms shall be no more than 6 days before randomization.
• SARS-CoV-2 infection should be verified by PCR at the screening.
• Ability to follow the protocol and fulfill all the clinical study procedures.
• Ability and willingness of the subjects and their sexual partners with retained childbearing potential to use reliable contraception methods throughout the study and for 3 months after the treatment completion.
• Willingness not to take alcohol throughout the study.

Exclusion criteria

• Age < 18 and > 60 years.
• Any etiotropic therapy of coronavirus SARS-CoV-2 (COVID-19) infection prior to the study.
• Moderate infection with respiratory failure, severe or extremely severe SARS-CoV-2 (COVID-19) disease.
• Respiratory failure (RR > 30/min, SpO2 ≤ 93 %) or the need for mechanical ventilation at the screening.
• Decreased level of consciousness (disorientation of place, time and personality), agitation at the screening.
• Unstable hemodynamics (systolic BP < 100 mm Hg or diastolic BP < 60 mm Hg) found at the screening.
• Subtotal diffuse ground-glass induration of pulmonary tissue and pulmonary consolidation combined with reticular changes; involvement of ≥ 75 % of lung parenchyma; hydrothorax (CT findings corresponding to ≥ CT-4 according to Department of Health of Moscow guidelines).
• Presence of comorbidities:

• moderate or severe chronic obstructive pulmonary disease or asthma;
• severe chronic cardiovascular disorders (arrhythmia or conduction disorders, implanted pacemaker device, myocardial infarction or unstable angina in the medical history, heart failure);
• immunocompromised subjects (HIV, cancer, autoimmune diseases, immunodepressant therapy);
• severe obesity (body mass index [BMI] ≥ 40);
• diabetes mellitus;
• chronic renal failure;
• chronic moderate or severe hepatic disorders.
• Any of the following abnormal laboratory tests at the screening: AST or ALT level > 2.5 x upper normal level (UNL), platelet count < 50х109/L.
• Any history findings which, in the investigator's opinion, may complicate the interpretation of the study results or generate an additional risk for the subject due to his/her participation in the study.
• More than 2 CT diagnostic procedures within the last 6 months prior to randomization (except for chest CT no earlier than 4 days prior to enrollment).
• The subject takes the products significantly inhibiting CYP28С, and administration those products cannot be interrupted for the study duration.
• Malabsorption syndrome or another clinically relevant gastrointestinal disease which may affect the study product absorption (uncontrollable vomiting, diarrhea, ulcerative colitis, etc.).
• Pregnancy or breast-feeding; women with probable pregnancy at the screening, those planning to conceive during the study.
• Known (from the history) or suspected alcohol or psychotropic drug abuse; medicinal or illicit drug addiction.
• Mental disorders including those in the medical history.
• Condition or disease which, according to the investigator or medical monitor, will compromise the subject's safety or affect assessment of the study product safety.