<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04501783</url>
  </required_header>
  <id_info>
    <org_study_id>TL-FVP-t-01</org_study_id>
    <nct_id>NCT04501783</nct_id>
  </id_info>
  <brief_title>Study of Efficacy and Safety of TL-FVP-t vs. SOC in Patients With Mild to Moderate COVID-19</brief_title>
  <official_title>Randomized Open-label Multicenter Parallel-group Study of Efficacy and Safety of TL-FVP-t vs. Standard of Care Therapy in Patients With Mild to Moderate Coronavirus Disease (SARS-CoV-2/COVID-19)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>R-Pharm</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>R-Pharm</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomized open-label multicenter parallel-group study of efficacy and safety of TL-FVP-t vs.&#xD;
      standard of care therapy in patients with mild to moderate coronavirus disease&#xD;
      (SARS-CoV-2/COVID-19)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was an open label, randomized, controlled, multicenter Phase 3 study of TL-FVP-t in&#xD;
      outpatients and inpatients with mild to moderate COVID-19. After stratification by the&#xD;
      severity of their disease (mild or moderate), age (18-44 or ≥ 45 years) and CT severity&#xD;
      subjects were randomized at a rate of 2:1 to receive either TL-FVP-t + standard concomitant&#xD;
      therapy or standard ethiptropic therapy (standard of care - SOC) including standard&#xD;
      concomitant therapy. Standard ethiptropic therapy according to MoH of Russian Federation&#xD;
      included umifenovir + intranasal recombinant interferon alpha, hydroxichloroquine, or&#xD;
      chloroquine.&#xD;
&#xD;
      The dose regimen was the following: TL-FVP-t at a dose of 1800 mg BID on the Day 1 followed&#xD;
      by 800 mg BID during the next 9 days. The study included the period of therapy (10 days) and&#xD;
      follow-up period (18 days).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 20, 2020</start_date>
  <completion_date type="Actual">August 4, 2020</completion_date>
  <primary_completion_date type="Actual">July 29, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to clinical improvement</measure>
    <time_frame>through Day 28</time_frame>
    <description>To determine the effect of TL-FVP-t vs. SOC on time to clinical improvement. The clinical improvement is defined as reduction on at least 1 score of patient clinical status according to WHO 8-category Ordinal Scale for Clinical Improvement compared to screening</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to viral clearance</measure>
    <time_frame>through Day 28</time_frame>
    <description>To determine the effect of TL-FVP-t vs. SOC on time to viral clearance of SARS-CoV-2 virus as measured by PCR in oropharyngeal sampling</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of clinical improvement at separate time points</measure>
    <time_frame>Day 7</time_frame>
    <description>To determine the effect of TL-FVP-t vs. SOC on proportion of subjects (%) with clinical improvement according to WHO 8-category Ordinal Scale for Clinical Improvement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of viral clearance at separate time points</measure>
    <time_frame>Days 5 and 7</time_frame>
    <description>To determine the effect of TL-FVP-t vs. SOC on a proportion of subjects (%) with viral clearance of SARS-CoV-2 virus as measured by PCR in oropharyngeal sampling at separate time points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to body temperature normalization</measure>
    <time_frame>through Day 28</time_frame>
    <description>To determine the effect of TL-FVP-t vs. SOC on time to body temperature normalization determined as body temperature &lt; 37°C without antipyretics for at least 48 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of resolution of lung changes on CT</measure>
    <time_frame>Day 14</time_frame>
    <description>To determine the effect of TL-FVP-t vs. SOC on a proportion of subjects (%) with resolution of lung changes on CT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of adverse drug reactions (ADR) and serious ADR</measure>
    <time_frame>through Day 28</time_frame>
    <description>To determine the effect of TL-FVP-t vs. SOC on a proportion of subjects (%) with ADR and serious ADR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of severe ADR</measure>
    <time_frame>through Day 28</time_frame>
    <description>To determine the effect of TL-FVP-t vs. SOC on a proportion of subjects (%) with severe ADR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate therapy termination due to ADR</measure>
    <time_frame>through Day 28</time_frame>
    <description>To determine the effect of TL-FVP-t vs. SOC on a proportion of subjects (%) discontinued therapy due ADR</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">168</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>TL-FVP-t (favipiravir) Treatment Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Day 1: favipiravir 1800 mg BID plus Standard of Care (SOC); Days 2-10: 800 mg BID plus SOC.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of Care including etiotropic therapy according to MoH of Russian Federation Recomendations for COVID-19 (umifenovir + intranasal recombinant interferon alpha, or hydroxychloroquine, or chloroquine, or mefloquine in recomended regimen) up to10 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Favipiravir</intervention_name>
    <description>TL-FVP-t will be administered orally</description>
    <arm_group_label>TL-FVP-t (favipiravir) Treatment Arm</arm_group_label>
    <other_name>TL-FVP-t</other_name>
    <other_name>Koronavir</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of care (SOC)</intervention_name>
    <description>SOC will include standard etiotropic therapy (umifenovir + intranasal recombinant interferon alpha, or hydroxychloroquine, or chloroquine) according to MoH of Russian Federation recomendations for COVID-19</description>
    <arm_group_label>Standard of Care Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>standard concomitant therapy</intervention_name>
    <description>Standard of care according to MoH of Russian Federation recomendation for COVID-19</description>
    <arm_group_label>Standard of Care Arm</arm_group_label>
    <arm_group_label>TL-FVP-t (favipiravir) Treatment Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Informed consent form signed.&#xD;
&#xD;
          2. Males and females aged 18-60 years;&#xD;
&#xD;
          3. Diagnosis of coronavirus disease caused by SARS-CoV-2 (COVID-19) in a mild or moderate&#xD;
             form (without respiratory failure).&#xD;
&#xD;
          4. Duration of infection symptoms shall be no more than 6 days before randomization.&#xD;
&#xD;
          5. SARS-CoV-2 infection should be verified by PCR at the screening.&#xD;
&#xD;
          6. Ability to follow the protocol and fulfill all the clinical study procedures.&#xD;
&#xD;
          7. Ability and willingness of the subjects and their sexual partners with retained&#xD;
             childbearing potential to use reliable contraception methods throughout the study and&#xD;
             for 3 months after the treatment completion.&#xD;
&#xD;
          8. Willingness not to take alcohol throughout the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age &lt; 18 and &gt; 60 years.&#xD;
&#xD;
          2. Any etiotropic therapy of coronavirus SARS-CoV-2 (COVID-19) infection prior to the&#xD;
             study.&#xD;
&#xD;
          3. Moderate infection with respiratory failure, severe or extremely severe SARS-CoV-2&#xD;
             (COVID-19) disease.&#xD;
&#xD;
          4. Respiratory failure (RR &gt; 30/min, SpO2 ≤ 93 %) or the need for mechanical ventilation&#xD;
             at the screening.&#xD;
&#xD;
          5. Decreased level of consciousness (disorientation of place, time and personality),&#xD;
             agitation at the screening.&#xD;
&#xD;
          6. Unstable hemodynamics (systolic BP &lt; 100 mm Hg or diastolic BP &lt; 60 mm Hg) found at&#xD;
             the screening.&#xD;
&#xD;
          7. Subtotal diffuse ground-glass induration of pulmonary tissue and pulmonary&#xD;
             consolidation combined with reticular changes; involvement of ≥ 75 % of lung&#xD;
             parenchyma; hydrothorax (CT findings corresponding to ≥ CT-4 according to Department&#xD;
             of Health of Moscow guidelines).&#xD;
&#xD;
          8. Presence of comorbidities:&#xD;
&#xD;
               1. moderate or severe chronic obstructive pulmonary disease or asthma;&#xD;
&#xD;
               2. severe chronic cardiovascular disorders (arrhythmia or conduction disorders,&#xD;
                  implanted pacemaker device, myocardial infarction or unstable angina in the&#xD;
                  medical history, heart failure);&#xD;
&#xD;
               3. immunocompromised subjects (HIV, cancer, autoimmune diseases, immunodepressant&#xD;
                  therapy);&#xD;
&#xD;
               4. severe obesity (body mass index [BMI] ≥ 40);&#xD;
&#xD;
               5. diabetes mellitus;&#xD;
&#xD;
               6. chronic renal failure;&#xD;
&#xD;
               7. chronic moderate or severe hepatic disorders.&#xD;
&#xD;
          9. Any of the following abnormal laboratory tests at the screening: AST or ALT level &gt;&#xD;
             2.5 x upper normal level (UNL), platelet count &lt; 50х109/L.&#xD;
&#xD;
         10. Any history findings which, in the investigator's opinion, may complicate the&#xD;
             interpretation of the study results or generate an additional risk for the subject due&#xD;
             to his/her participation in the study.&#xD;
&#xD;
         11. More than 2 CT diagnostic procedures within the last 6 months prior to randomization&#xD;
             (except for chest CT no earlier than 4 days prior to enrollment).&#xD;
&#xD;
         12. The subject takes the products significantly inhibiting CYP28С, and administration&#xD;
             those products cannot be interrupted for the study duration.&#xD;
&#xD;
         13. Malabsorption syndrome or another clinically relevant gastrointestinal disease which&#xD;
             may affect the study product absorption (uncontrollable vomiting, diarrhea, ulcerative&#xD;
             colitis, etc.).&#xD;
&#xD;
         14. Pregnancy or breast-feeding; women with probable pregnancy at the screening, those&#xD;
             planning to conceive during the study.&#xD;
&#xD;
         15. Known (from the history) or suspected alcohol or psychotropic drug abuse; medicinal or&#xD;
             illicit drug addiction.&#xD;
&#xD;
         16. Mental disorders including those in the medical history.&#xD;
&#xD;
         17. Condition or disease which, according to the investigator or medical monitor, will&#xD;
             compromise the subject's safety or affect assessment of the study product safety.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Medical center LLC &quot;Neuroprofi&quot;</name>
      <address>
        <city>Korolev</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal budgetary institution of science &quot;Central Research Institute of Epidemiology&quot; of Russian Federal Supervision Service for Consumer Rights Protection and People's Welfare</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical centers JSC &quot;Medsi Group of Companies&quot;</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State budgetary institution of health care of the city of Moscow &quot;City Clinical Hospital №52 of the Moscow City Healthcare Department&quot;</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State budgetary institution of health care of the city of Moscow &quot;City Clinical Hospital №67 n.a. LA Vorokhobova of the Moscow City Healthcare Department&quot;</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State budgetary institution of health care of the city of Moscow &quot;Infectious Diseases Clinical Hospital №1 of the Moscow City Healthcare Department&quot;</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical center LLC &quot;Medical Center Eco-safety&quot;</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Petersburg State Budgetary Healthcare Institution &quot;City Hospital No. 40 of the Kurortny District&quot;</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Budgetary healthcare institution of the Voronezh region &quot;Voronezh Regional Clinical Hospital No. 1&quot;</name>
      <address>
        <city>Voronezh</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Budgetary Healthcare Institution of the Moscow Region &quot;Zhukovskaya City Clinical Hospital&quot;.</name>
      <address>
        <city>Zhukovskiy</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 5, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>January 18, 2023</last_update_submitted>
  <last_update_submitted_qc>January 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SARS-CoV-2</keyword>
  <keyword>Severe acute respiratory syndrome coronavirus 2</keyword>
  <keyword>2019-nCoV</keyword>
  <keyword>2019 novel coronavirus</keyword>
  <keyword>Respiratory disease</keyword>
  <keyword>lung disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Favipiravir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04501783
org study id: TL-FVP-t-01
nct id: NCT04501783
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Randomized open-label multicenter parallel-group study of efficacy and safety of TL-FVP-t vs.
      standard of care therapy in patients with mild to moderate coronavirus disease
      (SARS-CoV-2/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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time to clinical improvement
time frame: through Day 28
description: To determine the effect of TL-FVP-t vs. SOC on time to clinical improvement. The clinical improvement is defined as reduction on at least 1 score of patient clinical status according to WHO 8-category Ordinal Scale for Clinical Improvement compared to screening
measure: Time to viral clearance
time frame: through Day 28
description: To determine the effect of TL-FVP-t vs. SOC on time to viral clearance of SARS-CoV-2 virus as measured by PCR in oropharyngeal sampling
measure: Rate of clinical improvement at separate time points
time frame: Day 7
description: To determine the effect of TL-FVP-t vs. SOC on proportion of subjects (%) with clinical improvement according to WHO 8-category Ordinal Scale for Clinical Improvement
measure: Rate of viral clearance at separate time points
time frame: Days 5 and 7
description: To determine the effect of TL-FVP-t vs. SOC on a proportion of subjects (%) with viral clearance of SARS-CoV-2 virus as measured by PCR in oropharyngeal sampling at separate time points
measure: Time to body temperature normalization
time frame: through Day 28
description: To determine the effect of TL-FVP-t vs. SOC on time to body temperature normalization determined as body temperature < 37°C without antipyretics for at least 48 hours.
measure: Rate of resolution of lung changes on CT
time frame: Day 14
description: To determine the effect of TL-FVP-t vs. SOC on a proportion of subjects (%) with resolution of lung changes on CT
measure: Rate of adverse drug reactions (ADR) and serious ADR
time frame: through Day 28
description: To determine the effect of TL-FVP-t vs. SOC on a proportion of subjects (%) with ADR and serious ADR
measure: Rate of severe ADR
time frame: through Day 28
description: To determine the effect of TL-FVP-t vs. SOC on a proportion of subjects (%) with severe ADR
measure: Rate therapy termination due to ADR
time frame: through Day 28
description: To determine the effect of TL-FVP-t vs. SOC on a proportion of subjects (%) discontinued therapy due ADR
arm group label: TL-FVP-t (favipiravir) Treatment Arm
arm group type: Experimental
description: Day 1: favipiravir 1800 mg BID plus Standard of Care (SOC); Days 2-10: 800 mg BID plus SOC.
arm group label: Standard of Care Arm
arm group type: Active Comparator
description: Standard of Care including etiotropic therapy according to MoH of Russian Federation Recomendations for COVID-19 (umifenovir + intranasal recombinant interferon alpha, or hydroxychloroquine, or chloroquine, or mefloquine in recomended regimen) up to10 days
intervention type: Drug
intervention name: Favipiravir
description: TL-FVP-t will be administered orally
arm group label: TL-FVP-t (favipiravir) Treatment Arm
other name: TL-FVP-t
other name: Koronavir
intervention type: Drug
intervention name: Standard of care (SOC)
description: SOC will include standard etiotropic therapy (umifenovir + intranasal recombinant interferon alpha, or hydroxychloroquine, or chloroquine) according to MoH of Russian Federation recomendations for COVID-19
arm group label: Standard of Care Arm
intervention type: Drug
intervention name: standard concomitant therapy
description: Standard of care according to MoH of Russian Federation recomendation for COVID-19
arm group label: Standard of Care Arm
arm group label: TL-FVP-t (favipiravir) Treatment Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Favipiravir
sharing ipd: No