A Phase 3 blinded study to assess the efficacy and safety of Favipiravir vs placebo in Non-critical Hospitalized Patients with COVID-19 Pneumonia (PROVIR)

INTERVENTION: Trade Name: Favipiravir Tablets 200 mg ‐ Fabiflu Product Name: Favipiravir Pharmaceutical Form: Tablet INN or Proposed INN: FAVIPIRAVIR Current Sponsor code: 259793‐96‐9 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Coronavirus disease 2019 (COVID‐19 pneumonia) ; MedDRA version: 25.1 Level: LLT Classification code 10066740 Term: Acute respiratory tract infection System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: • To assess the clinical efficacy of favipiravir plus standard of care (SOC) compared to placebo plus SOC by reduction in clinical deterioration. Primary end point(s): Proportion of patients hospitalized requiring non‐invasive ventilation or high flow oxygen, mechanical ventilation, dialysis, ECMO or who are dead at any time from randomization up to Day 15. Secondary Objective: • To assess the impact of favipiravir in preventing COVID‐19 disease progression.; • To assess the impact of favipiravir on the duration of hospitalization, intensive care unit (ICU) admission, duration of stay in the ICU, mortality, and other healthcare resource use.; • To assess the virologic efficacy of favipiravir.; • To assess the safety and tolerability of favipiravir. Timepoint(s) of evaluation of this end point: Primary endpoint will be evaluated up to day 15. INCLUSION CRITERIA: 1. Adults aged >= 18 years. 2. Patient understands and agrees to comply with planned study procedures and provides informed consent prior to undergoing any study procedures. 3. Hospitalized for symptoms associated with non‐critical COVID‐19 pneumonia with an interval between symptoms onset and randomization preferably until 4 days but no longer than 10 days. 4. Virologic confirmation of SARS‐CoV‐2 infection within 72 hours of randomization as determined by a valid test on respiratory tract specimens. 5. Category 4 or 5 on the WHO 10‐point Ordinal Scale for Clinical Progression at time of randomization (hospitalized, with no oxygen therapy, or with oxygen by mask or nasal prongs). 6. Radiological evidence of lung infiltrates consistent with COVID‐19 related pneumonia. 7. Women of childbearing potential must have a negative serum pregnancy test. 8. Female and male patients of childbearing potential must agree to use highly effective methods of SECONDARY OUTCOME: Secondary end point(s): Efficacy; ; To assess the impact of favipiravir in preventing COVID‐19 disease progression:; • Proportion of patients hospitalized requiring non‐invasive ventilation, mechanical ventilation, ECMO, dialysis or who are dead at Day 29 and at Day 90.; • Clinical status as assessed with the WHO 10‐point Ordinal Scale for Clinical ‐Progression at Day 8, Day 15 and Day 90.; • Change in clinical status as assessed with the WHO 10‐point Ordinal Scale for Clinical Progression at Day 8, Day 15 and Day 90 relative to Baseline.; • Time to change in 1 or in 2 levels/points of the National Early Warning Score 2 (NEWS2) scoring system up to Day 29.; ; To assess the impact of favipiravir on the duration of hospitalization, ICU admission, duration of stay in the ICU, mortality, and other healthcare resource use:; • Duration of hospitalization (days) up to and including Day 90.; • Proportion of patients in ICU at Day 8, Day 15, Day 29 and Day 90; Duration of stay in the ICU up to and including Day 90).; • Overall survival up to and including Day 90.; • Proportion of patients requiring any supplemental oxygen therapy at Day 8, Day 15, Day 29 and Day 90.; •Duration of oxygen therapy (days) up to Day 90.; •Proportion of patients requiring non‐invasive ventilation or high flow oxygen, mechanical ventilation, dialysis or ECMO during hospitalization.; • Duration of non‐invasive ventilation or high flow oxygen (days) up to Day 90.; • Proportion of patients requiring invasive mechanical ventilation or ECMO during hospitalization.; • Duration of invasive mechanical ventilation or ECMO (days) up to Day 90.; • Proportion of patients requiring dialysis during hospitalization.; • Duration of dialysis (days) up to Day 90.; ; To assess the virologic efficacy of favipiravir.; • Change from Baseline in quantitative SARS‐CoV‐2 viral load by RT‐PCR at Days 3, 5, 8, 10, 15, and 29.; • Proportion of patients with viral clearance at Day 8, Day 10 or Day of Discharge, Day 15, and Day 29.; ; ; Safety; ; To assess the safety and tolerability of favipiravir:; • Treatment‐emergent adverse events (TEAEs), serious adverse events (SAEs) including deaths,and premature discontinuations of study drug up to Day 90/End of Follow‐up.; • Clinically significant changes in laboratory parameters (hematology, chemistry, hepatic, coagulation, urinalysis).; • Clinically significant changes in electrocardiogram (ECG) results.; • Clinically significant changes in vital signs.; • Clinically significant changes in physical examination results. Timepoint(s) of evaluation of this end point: Secondary endpoints will be evaluated on days 3, 5, 8, 10, 15, 29 and 90, depending on the endpoint