The study is Phase II/III and consists of pilot and pivotal stages. The objective of the pilot stage is to conduct a preliminary assessment of the efficacy and safety of Favipiravir, and to select the optimal dosing regimen to study during the pivotal stage. The objective of the pivotal stage is to assess the efficacy and safety of Favipiravir compared with the Standard of care (SOC) in hospitalized patients with moderate to severe COVID-19 pneumonia.
At the pilot stage: upon signing the informed consent form and screening, 60 eligible patients with polymerase chain reaction (PCR) confirmed COVID-19 pneumonia are randomized at a 1:1:1 ratio to receive either Favipiravir 1600 mg twice a day (BID) on Day 1 followed by 600 mg BID on Days 2-14 (1600/600 mg), or Favipiravir 1800 mg BID on Day 1 followed by 800 mg BID on Days 2-14 (1800/800 mg), or SOC. At the pivotal stage: additional 270 eligible patients are randomized at a 1:1 ratio to receive either Favipiravir (the dose regimen depends of the subject's weight) or SOC.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
330
200 mg coated tablets
Standard of Care will be prescribed in accordance with the recommended treatment regimens presented in the Russian guidelines for the prevention, diagnosis and treatment of COVID-19 according to the decision of the Investigator.
Republican Clinical Hospital
Makhachkala, Russia
"K+31" Clinic
Rate of viral elimination by Day 10 [pilot stage, dose selection]
Percent of patients with undetectable SARS-CoV-2 RNA level on Day 10
Time frame: 10 Days
Time to viral elimination [pivotal stage]
Median time to reach undetectable SARS-CoV-2 RNA level
Time frame: 28 Days
Time to clinical improvement [pivotal stage]
Median time reach clinical improvement (2 points of the Ordinal Scale for Clinical Improvement) or discharge from the hospital
Time frame: 28 Days
Rate of viral elimination
Percent of patients with undetectable SARS-CoV-2 RNA level
Time frame: Days 3, 5, 7, 9, and 11
Time to normalization of clinical symptoms
Median time \[days\] to reach normal levels of clinical indicators (body temperature, SpO2, breathing rate)
Time frame: 28 Days
Duration of oxygen therapy
Mean duration of oxygen therapy \[days\]
Time frame: 28 Days
Change in the level of lung damage according to CT
Change of lung damage level according to CT comparing to baseline \[% of patients\]
Time frame: Days 15, 22, and 29
Rate of transfer to the intensive care unit
Percent of patients transferred to the intensive care unit \[% of patients\]
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Moscow, Russia
"Khaven" Llc
Moscow, Russia
Central Clinical Hospital with Polyclinic
Moscow, Russia
Central Research Institute of Epidemiology
Moscow, Russia
City Clinical Hospital n.a. O.M. Filatov
Moscow, Russia
City Clinical Hospital named after S.S. Yudin
Moscow, Russia
City Clinical Hospital No. 24
Moscow, Russia
City Clinical Hospital No. 51
Moscow, Russia
First Moscow State Medical University n.a. I.M. Sechenov
Moscow, Russia
...and 12 more locations
Time frame: 28 days
Rate of the use of non-invasive lung ventilation
Percent of patients undergoing non-invasive lung ventilation \[% of patients\]
Time frame: 28 days
Rate of the use of mechanical ventilation
Percent of patients undergoing mechanical ventilation \[% of patients\]
Time frame: 28 days
Mortality
Percent of patients died within 28-days period \[% of patients\]
Time frame: 28 days
Peak plasma concentration (Cmax)
Determination of Cmax \[ng/ml\]
Time frame: Day 1
Time to peak plasma concentration (Tmax)
Determination of Tmax \[h\]
Time frame: Day 1
Area under the plasma concentration versus time curve (AUC0-t)
Determination of AUC0-t \[ng\*h/ml\]
Time frame: 10 days
Trough plasma concentration (Ctrough)
Determination of Ctrough \[ng/ml\]
Time frame: 10 days