Efesovir (FS-1) for COVID-19, Phase 2

Study Overview
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Brief Summary
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Study of the efficacy and safety of the new drug Efesovir in comparison with the drug Remdesivir in the treatment of patients hospitalized with COVID-19. The hypothesis of clinical study is the clinical efficacy of new drug Efesovir is 10% to 30% higher than of Remdesivir.

Official Title
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Randomized Controlled Open Study of Safety and Preliminary Efficiency of the Drug Efesovir (Oral Solution) for Coronavirus Infection (COVID-19)

Conditions
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Covid19

Intervention / Treatment
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* Drug: Efesovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: polymerase chain reaction (PCR) confirmed coronavirus infection (COVID-19) in hospitalized patients with severe risk factors in age from 18 years to 59 years, of both sexes, irrespective of national or ethnic origin the duration of the COVID-19 disease is no more than 10 days informed concent to participate in clinical trials informed concent to to use reliable contraceptive methods while participating in a clinical trial Exclusion Criteria: age less than 18 years old and over 59 years old pregnancy or breastfeeding hypersensitivity, allergy, intolerance to iodine, iodine-containing medicines hypersensitivity to Remdesivir or its components impaired consciousness, causing the impossibility of oral administration conditions or circumstances that, in the opinion of the investigator, may affect the patient's safety or the quality of the results obtained participation in another clinical trial, including in the period up to 2 months before this study signs of multiple organ failure alanine aminotransferase (ALT), aspartate aminotransferase (AST) is 5 or more times higher than normal thrombocytopenia below 100 * 10^9/ l decrease in glomerular filtration rate (GFR) less than 30 ml / min by 1.73 m2 chronic heart failure with reduced ejection fraction liver failure coagulopathy mechanical ventilation for 48 hours or more extracorporeal membrane oxygenation (ECMO) disseminated intravascular coagulation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are assigned to the one of two parallel groups: 1) treated with study drug Efesovir; 2) treated with referent drug Remdesivir.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Efesovir<br>The patients of experimental arm take study drug Efesovir twice a day as an antiviral therapy in dose 0.125 ml / kg. Daily dose of Efesovir: 0.250 ml / kg. Duration of treatment is 5 - 10 days, depending on the severity of the disease. | Drug: Efesovir<br>* Antiviral therapy of COVID19 with Efesovir oral solution in dose 0.125 ml / kg two times per day. Duration of treatment is 5 - 10 days, depending on the severity of the disease.<br>* Other names: FS-1;|
| Active Comparator: Remdesivir<br>The patients are treated with the antiviral drug Remdesivir in dose 200 mg intravenously on the 1st day, then by 100 mg intravenously daily for 5 - 10 days, depending on the severity of the disease. | Drug: Efesovir<br>* Antiviral therapy of COVID19 with Efesovir oral solution in dose 0.125 ml / kg two times per day. Duration of treatment is 5 - 10 days, depending on the severity of the disease.<br>* Other names: FS-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response Rate | Clinical Response Rate is calculated as the number of trial subjects with effective treatment over the total number of subjects multiplied by 100. It is calculated in each study group. Measured in percents. The outcome is estimated among randomized subjects completed clinical study with the protocol requirements (per protocol population (PPP)). Clinical response is evaluated as effective treatment if: all signs and symptoms of COVID19 are resolved or improved with no worsening or appearance of new signs and symptoms; there is no requirement for additional antiviral of antibacterial therapy; chest roentgenograms (CT scans) are improved. The outcome is assessed in day 21 from the start of Study Drug treatment (visits 13). | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early Clinical Response Rate | Early clinical response rate defined as complete resolution or significant improvement of at least 2 of 4 leading baseline signs and symptoms within 72 hours after the start of Study (Referent) Drug treatment. It is estimated in the Intent to Treat (ITT) population. The outcome is measured in percents. | 72 hours (3 days) of study drug treatment | 
| Early Clinical Response Rate in pneumonia | The outcome is estimated in patients with pneumonia due to coronavirus infection (modified ITT population). It is defined as complete resolution or significant improvement of at least 2 of 4 main clinical symptoms of pneumonia (cough, shortness of breath, chest pain, sputum) within 72 hours after the start of Study (or Referent) Drug treatment. The outcome is measured in percents. The percentage of subjects with an early clinical response to pneumonia in the compared groups is statistically estimated. | 72 hours (3 days) of study drug treatment | 
| Percentage of clinically stable patients | Percentage of patients at Day 3 who are clinically stable. Clinical stability defined as: Blood oxygen saturation >= 93% Temperature <=38.0°C Heart rate <=100 beats per minute Respiratory rate <=25 per minute Systolic blood pressure ≥90 mm Hg Ability to maintain oral intake Normal mental status (oriented to person, place or time) A patient is considered to be clinically stable if all stability criteria are met. The outcome is assessed in ITT population. The difference between groups in the percentage of clinically stable patients from the total number of study subjects in the group is statistically evaluated. | 72 hours (3 days) of study drug treatment | 
| Survival rate | Percentage of participants surviving at day 21. The indicator is calculated as the number of live subjects at the last visit (day 21) divided by the total number of study subjects in the group multiplied by 100. The outcome is estimated among subjects who completed the study in compliance with the protocol (per protocol population (PPP)). | 21 days | 
| Clinical Status Change | The clinical status is determined by the ordinal scale: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities and/or requiring home oxygen Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation Death Clinical status is assessed in ITT population. The outcome is recorded at all visits, starting from the day of randomization. A decrease in points indicates the effectiveness of treatment. When the indicator changes during the day, the worst score of the day is recorded. Statistical analysis is performed on the Day 7 from the start Study Drug treatment, comparing with the score at randomization. | 7 days | 
| Adverse Events (AE) | The safety of Study Drug (Referent Drug) will be assessed by adverse event and serious adverse event monitoring. | up to 21 days | 
| Thyroid gland function | Changes in laboratory parameters of thyroid gland function (hormones) at the last visit in comparison with the baseline data (thyroid stimulating hormone (TSH), free triiodothyronine (FT3)). | Day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID19, viral pneumonia, FS-1, Efesovir