<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/NCT04487574</url>
  </required_header>
  <id_info>
    <org_study_id>XC221-03-02-2020</org_study_id>
    <nct_id>NCT04487574</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Efficacy and Safety of XC221 in Patients With COVID-19</brief_title>
  <official_title>A Multicenter, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of XC221, Tablets, 100 mg in Patients With COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>RSV Therapeutics LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>RSV Therapeutics LLC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The innovative drug XC221 100 mg tablet is designed for the treatment of COVID-19 (SARS-CoV-2&#xD;
      infection). A multicenter, adaptive, randomized, double-blind, placebo-controlled Phase III&#xD;
      clinical study is aimed to assess the efficacy and safety of XC221 100 mg tablet, in COVID-19&#xD;
      patients during a 14-day treatment.&#xD;
&#xD;
      The primary objective of the study is to demonstrate the efficacy of XC221 100 mg tablet (200&#xD;
      mg daily dose) in achieving clinical improvement of COVID-19 symptoms.&#xD;
&#xD;
      The secondary objective of the study is to evaluate the safety of XC221 100 mg tablet (200 mg&#xD;
      daily dose) in COVID-19 patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      11 Russian centers will participate in this study. The trail will consist of three periods:&#xD;
      screening (duration not more than 1 day, it may coincide with the randomization visit and&#xD;
      beginning of drug administration), treatment period (14 days) and follow-up period (14 ± 1&#xD;
      days after completion of treatment with XC221 / Placebo). The duration of participation in&#xD;
      the study for each patient will be no more than 30 days.&#xD;
&#xD;
      118 eligible patients with confirmed COVID-19 will be randomized into two groups (Group A and&#xD;
      Group B) in a 1:1 ratio: Group A - XC221 200 mg daily (59 patients); Group В - Placebo (59&#xD;
      patients).&#xD;
&#xD;
      During the treatment period (14 days), 1 tablet of XC221 / Placebo will be administered 2&#xD;
      times a day in addition to the standard of care (SoC) for COVID-19 according to The Temporary&#xD;
      guidelines for the prevention, diagnosis and treatment of SARS-CoV-2 infection of the&#xD;
      Ministry of Health of the Russian Federation (the MoH Temporary Guidelines). The follow-up&#xD;
      period will last for 14 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 25, 2020</start_date>
  <completion_date type="Actual">October 29, 2020</completion_date>
  <primary_completion_date type="Actual">October 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>Double (Participant, Investigator)</masking>
    <masking_description>Tablets identical in terms of composition, appearance and labeling to XC221 tablets, but without active substance will be used as Placebo.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Patient rate with a transition to category 3 or lower according to the WHO scale by Day 14 after the beginning of drug administration.</measure>
    <time_frame>Day 1 - Day 14</time_frame>
    <description>The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time till clinical improvement, which is described by presence of all of the following factors during 48 hours in a row.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>Body temperature ≤ 37.5°C without using NSAIDs and / or paracetamol;&#xD;
RR ≤ 22 / min without oxygen therapy;&#xD;
SpO2 ≥ 95% without oxygen therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate with clinical improvement by day 2-28. Presence of all of the following factors during 48 hours in a row.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>Body temperature ≤ 37.5°C without using NSAIDs and / or paracetamol;&#xD;
RR ≤ 22 / min without oxygen therapy;&#xD;
SpO2 ≥ 95% without oxygen therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate with a negative test result for SARS-CoV-2 by Day 7±1, 15±1, 21 ±1 and 28 ± 1.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospitalization.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate transferred to the intensive care unit (ICU) during hospitalization.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of ICU stay.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate with ARDS during hospitalization.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of a fatal outcome.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate requiring oxygen therapy by Day 2-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate requiring high-flow oxygen therapy by Day 2-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate requiring non-invasive ventilation by Day 2-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate requiring invasive ventilation by Day 2-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate requiring extracorporeal membrane oxygenation (EMO) by Day 2-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The total duration of oxygen therapy by the last day of hospitalization.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The total duration of high-flow oxygen therapy by the last day of hospitalization.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The total duration of non-invasive ventilation by the last day of hospitalization.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The total duration of invasive ventilation of lungs by the last day of hospitalization.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The total duration of EMO by the last day of hospitalization.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate with Sp02 &gt; 95% by Day 2-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average alteration of Sp02 by Day 2-28 from baseline.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average time to reach SpO2 ≥ 95%.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate with RR &lt; 22 / min by Day 2-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average alteration in RR by Day 2-28 from baseline.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average time to reach RR ≤ 22 / min.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate with body temperature &lt; 37.5°C by Day 2-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average alteration in body temperature by Day 2-28 from baseline.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average time until the patient reaches a body temperature of ≤37.5°C.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate with CT-1 according to CT data by Day 2-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average alteration in CT data by 1 point in terms of severity (CT-1, CT-2, CT-3, CT-4) by Day 7, 10, 15, 18, 21 and 28 compared to the baseline value.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average time to reach CT-1 according to CT data.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate with a score &lt; 2 according to the Daytime and Nighttime Cough Scale by Day 2-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in Daytime and Nighttime Cough scores by Day 2-28 from baseline.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average time to reach &lt; 2 points when assessed according to the Daytime and Nighttime Cough Scale.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate with a score &lt; 1 for each symptom (general fatigue, chest congestion, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale by Day 2-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average change in score for each symptom (general fatigue, chest congestion, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale by Day 2-28 from baseline.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average time to reach a score of &lt; 1 for each symptom (general fatigue, feeling of congestion in the chest, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate with a transition decrease to category 3 or lower according to the WHO scale by Day 2-13 and Day 15-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean WHO grade change by Day 2-28 from baseline.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average time to reach the 3rd category or below according to the WHO scale.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient rate with a NEWS score &lt; 2 by Day 2-28.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average change in NEWS score by Day 2-28 from baseline.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average time to reach a NEWS score ≤ 2.</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Concentration of IL-6 on Days 3 ± 1, 7 ± 1, 15 ± 1.</measure>
    <time_frame>Day 1 - Day 15</time_frame>
    <description>(Search Outcome)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">118</enrollment>
  <condition>SARS-CoV-2 Infection</condition>
  <arm_group>
    <arm_group_label>XC221</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>XC221 100 mg orally.&#xD;
1 tablet of XC221 100 mg 2 times a day during 14 days of treatment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo orally.&#xD;
1 tablet of Placebo 2 times a day during 14 days of treatment period</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>XC221</intervention_name>
    <description>Participants will receive XC221 100 mg 2 times a day during 14 days</description>
    <arm_group_label>XC221</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive Placebo 2 times a day during 14 days</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed Informed Consent Form.&#xD;
&#xD;
          2. Patients of both sexes aged 18 to 75 years inclusive.&#xD;
&#xD;
          3. Diagnosed COVID-19 based on:&#xD;
&#xD;
               -  positive laboratory tests confirming the SARS-CoV-2 presence, performed no&#xD;
                  earlier than 14 days before hospitalization. It is allowed to determine the&#xD;
                  SARS-CoV-2 by the PCR or by another method according to the MoH Temporary&#xD;
                  Guidelines; and / or&#xD;
&#xD;
               -  bilateral alterations in lungs, typical for COVID-19, according to CT scan of the&#xD;
                  chest.&#xD;
&#xD;
          4. Patients with moderate or severe form of disease (t &gt; 38.0°C; respiratory rate (RR)&#xD;
             &gt;22 / min; Sp02 &lt;95%) not requiring non-invasive / invasive ventilation and / or&#xD;
             high-flow oxygenation (HFNT), and / or extracorporeal membrane oxygenation (EMO) at&#xD;
             the time of screening and randomization (based on the MoH Temporary Guidelines).&#xD;
&#xD;
          5. Patients requiring oxygen therapy (oxygenation through a nasal cannula, a simple&#xD;
             facemask or other similar oxygen delivery device) with a category &quot;4&quot; according to the&#xD;
             WHO scale.&#xD;
&#xD;
          6. Time from hospitalization to the first drug administration should not exceed 48 hours.&#xD;
             This item is to be assessed only when re-evaluating the inclusion / exclusion criteria&#xD;
             at the Randomization visit and treatment initiation.&#xD;
&#xD;
          7. Disease duration is no more than 7 full days since the moment of appearing one or more&#xD;
             of the symptoms below until the first dose of the drug administration:&#xD;
&#xD;
               -  temperature increase;&#xD;
&#xD;
               -  dry cough or cough with little phlegm;&#xD;
&#xD;
               -  shortness of breath;&#xD;
&#xD;
               -  myalgia;&#xD;
&#xD;
               -  fatigue;&#xD;
&#xD;
               -  feeling of congestion in the chest;&#xD;
&#xD;
               -  reduced sense of smell and / or taste.&#xD;
&#xD;
          8. For women only: negative pregnancy test result. Pregnancy testing is not required for&#xD;
             women of not childbearing potential (WONCBP): women who are in menopause (defined as&#xD;
             an absence of menstruation for at least 2 years or more), or women who undergone&#xD;
             surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation), or&#xD;
             women with a clinical diagnosis of &quot;infertility&quot;. The presence of surgical&#xD;
             sterilization and infertility should be confirmed by patient's claim or by relevant&#xD;
             document confirming this condition.&#xD;
&#xD;
          9. Consent to use reliable method of contraception throughout the study period.&#xD;
&#xD;
         10. Patients who are able to understand and comply with treatment and procedures during&#xD;
             the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known or suspected hypersensitivity to the active substance or to excipients of the&#xD;
             drug XC221 or placebo&#xD;
&#xD;
          2. Known or suspected hypersensitivity to standard therapy drugs specified in The MoH&#xD;
             Temporary Guidelines.&#xD;
&#xD;
          3. Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.&#xD;
&#xD;
          4. Presence or suspicion of oncological diseases by the day of criteria assessment or in&#xD;
             medical history (within the last 2 years).&#xD;
&#xD;
          5. Presence of autoimmune diseases by the day of criteria assessment or in medical&#xD;
             history.&#xD;
&#xD;
          6. Neutropenia (0.5 * 10^9 /l).&#xD;
&#xD;
          7. Exceeding the upper limit of normal for ALT and AST by 5 times or more.&#xD;
&#xD;
          8. Thrombocytopenia 50000 / mm^3.&#xD;
&#xD;
          9. Pregnancy.&#xD;
&#xD;
         10. Lactation.&#xD;
&#xD;
         11. Presence of serious lung diseases, including, but not limited to the following&#xD;
             diseases: moderate and severe bronchial asthma, severe and extremely severe COPD,&#xD;
             interstitial lung disease, pulmonary hypertension, pulmonary fibrosis, surgical&#xD;
             interventions on the lungs, tuberculosis (including suspicion of tuberculosis based on&#xD;
             the results of CT examination at screening).&#xD;
&#xD;
         12. Patients with type 1 diabetes mellitus and / or decompensated type 2 diabetes&#xD;
             mellitus.&#xD;
&#xD;
         13. Heart failure, NYHA functional class III - IV.&#xD;
&#xD;
         14. Chronic liver failure stage II (decompensated) and higher.&#xD;
&#xD;
         15. The need of renal replacement therapy at the time of inclusion of the patient.&#xD;
&#xD;
         16. Organ transplantation in medical history.&#xD;
&#xD;
         17. Medical history of epilepsy or the need for anticonvulsant therapy.&#xD;
&#xD;
         18. Major depressive disorder, anxiety, other mental disorders requiring medical&#xD;
             correction.&#xD;
&#xD;
         19. Acute cerebrovascular accident, stroke or transient ischemic attack within 90 days&#xD;
             before screening.&#xD;
&#xD;
         20. Administration of any antiviral and / or immunomodulatory drugs after the&#xD;
             manifestation of COVID-19, with the exception of those specified in the MoH Temporary&#xD;
             Guidelines.&#xD;
&#xD;
         21. Any immunosuppressive therapy (including tocilizumab / sarilumab) within 90 days prior&#xD;
             to randomization, or the need of immunosuppressive therapy at the time of&#xD;
             randomization.&#xD;
&#xD;
         22. Administration of systemic glucocorticosteroids within 90 days prior to randomization,&#xD;
             or the need of systemic glucocorticosteroids at the time of randomization.&#xD;
&#xD;
         23. Administration of vaccines against viral infections within 90 days prior to&#xD;
             randomization.&#xD;
&#xD;
         24. Patients receiving other experimental drugs, drugs not approved in the Russian&#xD;
             Federation, or participating in other clinical trials within 30 days before screening.&#xD;
&#xD;
         25. Patients abusing alcohol or psychotropic drugs and other drugs by the day of criteria&#xD;
             assessment or during the last year.&#xD;
&#xD;
         26. Patients with other serious, unstable, or clinically significant medical or&#xD;
             psychological conditions that, in the opinion of the investigator, may preclude the&#xD;
             patient's participation in the study.&#xD;
&#xD;
         27. Expected death within 48 hours after randomization.&#xD;
&#xD;
         28. Expected hospital discharge within 48 hours of randomization.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Municipal Budgetary Institution of Healthcare &quot;Central City Hospital of Novoshakhtinsk&quot;</name>
      <address>
        <city>Novoshakhtinsk</city>
        <state>Rostov Region</state>
        <zip>346918</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Petersburg State Budgetary Institution of Healthcare &quot;City Hospital No. 40 of Kurortny District&quot;</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197706</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Petersburg State Budgetary Institution of Healthcare &quot;City Pokrovskaya Hospital&quot; (4th Cardiology Department)</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>199106</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Petersburg State Budgetary Institution of Healthcare &quot;City Pokrovskaya Hospital&quot;</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>199106</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional State Budgetary Institution of Healthcare &quot;Medical-Sanitary Unit No. 2&quot;</name>
      <address>
        <city>Tomsk</city>
        <zip>634040</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <last_update_submitted>July 25, 2023</last_update_submitted>
  <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID19</keyword>
  <keyword>Coronavirus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_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/NCT04487574
org study id: XC221-03-02-2020
nct id: NCT04487574
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The innovative drug XC221 100 mg tablet is designed for the treatment of COVID-19 (SARS-CoV-2
      infection). A multicenter, adaptive, randomized, double-blind, placebo-controlled Phase III
      clinical study is aimed to assess the efficacy and safety of XC221 100 mg tablet, in COVID-19
      patients during a 14-day treatment.

      The primary objective of the study is to demonstrate the efficacy of XC221 100 mg tablet (200
      mg daily dose) in achieving clinical improvement of COVID-19 symptoms.

      The secondary objective of the study is to evaluate the safety of XC221 100 mg tablet (200 mg
      daily dose) in COVID-19 patients.
11 Russian centers will participate in this study. The trail will consist of three periods:
      screening (duration not more than 1 day, it may coincide with the randomization visit and
      beginning of drug administration), treatment period (14 days) and follow-up period (14 ± 1
      days after completion of treatment with XC221 / Placebo). The duration of participation in
      the study for each patient will be no more than 30 days.

      118 eligible patients with confirmed COVID-19 will be randomized into two groups (Group A and
      Group B) in a 1:1 ratio: Group A - XC221 200 mg daily (59 patients); Group В - Placebo (59
      patients).

      During the treatment period (14 days), 1 tablet of XC221 / Placebo will be administered 2
      times a day in addition to the standard of care (SoC) for COVID-19 according to The Temporary
      guidelines for the prevention, diagnosis and treatment of SARS-CoV-2 infection of the
      Ministry of Health of the Russian Federation (the MoH Temporary Guidelines). The follow-up
      period will last for 14 days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Tablets identical in terms of composition, appearance and labeling to XC221 tablets, but without active substance will be used as Placebo.
measure: Patient rate with a transition to category 3 or lower according to the WHO scale by Day 14 after the beginning of drug administration.
time frame: Day 1 - Day 14
description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).
measure: Time till clinical improvement, which is described by presence of all of the following factors during 48 hours in a row.
time frame: Day 1 - Day 28
description: Body temperature ≤ 37.5°C without using NSAIDs and / or paracetamol;
RR ≤ 22 / min without oxygen therapy;
SpO2 ≥ 95% without oxygen therapy.
measure: Patient rate with clinical improvement by day 2-28. Presence of all of the following factors during 48 hours in a row.
time frame: Day 1 - Day 28
description: Body temperature ≤ 37.5°C without using NSAIDs and / or paracetamol;
RR ≤ 22 / min without oxygen therapy;
SpO2 ≥ 95% without oxygen therapy.
measure: Patient rate with a negative test result for SARS-CoV-2 by Day 7±1, 15±1, 21 ±1 and 28 ± 1.
time frame: Day 1 - Day 28
measure: Duration of hospitalization.
time frame: Day 1 - Day 28
measure: Patient rate transferred to the intensive care unit (ICU) during hospitalization.
time frame: Day 1 - Day 28
measure: Duration of ICU stay.
time frame: Day 1 - Day 28
measure: Patient rate with ARDS during hospitalization.
time frame: Day 1 - Day 28
measure: Presence of a fatal outcome.
time frame: Day 1 - Day 28
measure: Patient rate requiring oxygen therapy by Day 2-28.
time frame: Day 1 - Day 28
measure: Patient rate requiring high-flow oxygen therapy by Day 2-28.
time frame: Day 1 - Day 28
measure: Patient rate requiring non-invasive ventilation by Day 2-28.
time frame: Day 1 - Day 28
measure: Patient rate requiring invasive ventilation by Day 2-28.
time frame: Day 1 - Day 28
measure: Patient rate requiring extracorporeal membrane oxygenation (EMO) by Day 2-28.
time frame: Day 1 - Day 28
measure: The total duration of oxygen therapy by the last day of hospitalization.
time frame: Day 1 - Day 28
measure: The total duration of high-flow oxygen therapy by the last day of hospitalization.
time frame: Day 1 - Day 28
measure: The total duration of non-invasive ventilation by the last day of hospitalization.
time frame: Day 1 - Day 28
measure: The total duration of invasive ventilation of lungs by the last day of hospitalization.
time frame: Day 1 - Day 28
measure: The total duration of EMO by the last day of hospitalization.
time frame: Day 1 - Day 28
measure: Patient rate with Sp02 > 95% by Day 2-28.
time frame: Day 1 - Day 28
measure: Average alteration of Sp02 by Day 2-28 from baseline.
time frame: Day 1 - Day 28
measure: Average time to reach SpO2 ≥ 95%.
time frame: Day 1 - Day 28
measure: Patient rate with RR < 22 / min by Day 2-28.
time frame: Day 1 - Day 28
measure: Average alteration in RR by Day 2-28 from baseline.
time frame: Day 1 - Day 28
measure: Average time to reach RR ≤ 22 / min.
time frame: Day 1 - Day 28
measure: Patient rate with body temperature < 37.5°C by Day 2-28.
time frame: Day 1 - Day 28
measure: Average alteration in body temperature by Day 2-28 from baseline.
time frame: Day 1 - Day 28
measure: Average time until the patient reaches a body temperature of ≤37.5°C.
time frame: Day 1 - Day 28
measure: Patient rate with CT-1 according to CT data by Day 2-28.
time frame: Day 1 - Day 28
measure: Average alteration in CT data by 1 point in terms of severity (CT-1, CT-2, CT-3, CT-4) by Day 7, 10, 15, 18, 21 and 28 compared to the baseline value.
time frame: Day 1 - Day 28
measure: Average time to reach CT-1 according to CT data.
time frame: Day 1 - Day 28
measure: Patient rate with a score < 2 according to the Daytime and Nighttime Cough Scale by Day 2-28.
time frame: Day 1 - Day 28
description: The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).
measure: Mean change in Daytime and Nighttime Cough scores by Day 2-28 from baseline.
time frame: Day 1 - Day 28
description: The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).
measure: Average time to reach < 2 points when assessed according to the Daytime and Nighttime Cough Scale.
time frame: Day 1 - Day 28
description: The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).
measure: Patient rate with a score < 1 for each symptom (general fatigue, chest congestion, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale by Day 2-28.
time frame: Day 1 - Day 28
description: The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.
measure: Average change in score for each symptom (general fatigue, chest congestion, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale by Day 2-28 from baseline.
time frame: Day 1 - Day 28
description: The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.
measure: Average time to reach a score of < 1 for each symptom (general fatigue, feeling of congestion in the chest, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale.
time frame: Day 1 - Day 28
description: The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.
measure: Patient rate with a transition decrease to category 3 or lower according to the WHO scale by Day 2-13 and Day 15-28.
time frame: Day 1 - Day 28
description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).
measure: Mean WHO grade change by Day 2-28 from baseline.
time frame: Day 1 - Day 28
description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).
measure: Average time to reach the 3rd category or below according to the WHO scale.
time frame: Day 1 - Day 28
description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).
measure: Patient rate with a NEWS score < 2 by Day 2-28.
time frame: Day 1 - Day 28
description: Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.
measure: Average change in NEWS score by Day 2-28 from baseline.
time frame: Day 1 - Day 28
description: Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.
measure: Average time to reach a NEWS score ≤ 2.
time frame: Day 1 - Day 28
description: Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.
measure: Concentration of IL-6 on Days 3 ± 1, 7 ± 1, 15 ± 1.
time frame: Day 1 - Day 15
description: (Search Outcome)
arm group label: XC221
arm group type: Experimental
description: XC221 100 mg orally.
1 tablet of XC221 100 mg 2 times a day during 14 days of treatment period.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo orally.
1 tablet of Placebo 2 times a day during 14 days of treatment period
intervention type: Drug
intervention name: XC221
description: Participants will receive XC221 100 mg 2 times a day during 14 days
arm group label: XC221
intervention type: Drug
intervention name: Placebo
description: Participants will receive Placebo 2 times a day during 14 days
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No