<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/NCT03301155</url>
  </required_header>
  <id_info>
    <org_study_id>MMH-AD-008</org_study_id>
    <nct_id>NCT03301155</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Anaferon for Children Efficacy in Prevention of Influenza and Other ARVI</brief_title>
  <official_title>International Multicenter Double-bind Placebo-controlled Randomized Parallel-group Clinical Trial of Anaferon for Children Efficacy in Prevention of Influenza and Other Acute Respiratory Viral Infections in Children During the Peaks of Seasonal Morbidity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Materia Medica Holding</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Materia Medica Holding</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>
      The objective of this study is to obtain additional data on the efficacy and safety of&#xD;
      12-week course of therapy with Anaferon for children for prevention of influenza and other&#xD;
      acute respiratory viral infections in children during the peaks of seasonal morbidity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Design: an international, multicenter, double-blind, placebo-controlled, randomized study in&#xD;
      parallel groups.&#xD;
&#xD;
      The study will enroll children of either gender aged of 1 month to 6 years old. Children can&#xD;
      participate in the study, regardless of the frequency of previous ARVI. A potential study&#xD;
      participant should not be in the incubation (if known), prodromal, acute/subacute periods of&#xD;
      any infectious disease (except for the recovery period). Schedule for enrollment of&#xD;
      participants: during the period of a seasonal rise in influenza/ARVI incidence in the Russian&#xD;
      Federation and the Republic of Uzbekistan. Screening and randomization of participants will&#xD;
      be subject to availability of official information on the incidence of influenza/ARVI in the&#xD;
      relevant study region.&#xD;
&#xD;
      The doctor makes the first visit to the participant in the medical center or at home. After&#xD;
      the parent/adoptive parent signs the information sheet (informed consent form), the doctor&#xD;
      evaluates the possibility of the participant being included in the trial. If the child meets&#xD;
      all the inclusion criteria and does not have all non-inclusion criteria, then he/she is&#xD;
      included in the study, the doctor fills in Clinical Research Form. At visit 1 (Day 1), the&#xD;
      participant is randomized into one of two groups: the 1st group participants will take&#xD;
      Anaferon for children according to the preventive regimen for 12 weeks; the 2nd group&#xD;
      participants will take Placebo according to the regimen of Anaferon for 12 weeks.&#xD;
&#xD;
      In total, the study participant will be observed for 12 weeks (screening and randomization up&#xD;
      to 1 day, preventive treatment for 12 weeks).&#xD;
&#xD;
      During the observation period at 4 (Visit 2), 8 (Visit 3) and 12 (Visit 4) weeks, three&#xD;
      visits are planned.&#xD;
&#xD;
      Visits 2 (Week 4 ± 3 days) and 3 (Week 8 ± 3 days) are conducted in the form of a telephone&#xD;
      survey of parents/adoptive parents about the participant's health status, presence/absence of&#xD;
      symptoms of influenza/ARVI, possible use of antibacterial drugs and/or hospitalization during&#xD;
      the course preventive therapy.&#xD;
&#xD;
      Visit 4 (Week 12 ± 3 days) is carried out at home or in a medical center; the doctor collects&#xD;
      complaints, examines the participant, registers concomitant therapy, assesses the compliance&#xD;
      of the therapy.&#xD;
&#xD;
      If in the period from 2 to 12 weeks a participant falls ill with influenza/ARVI, then he/she&#xD;
      prematurely completes participation in the study (as having reached the primary endpoint). A&#xD;
      participant is considered fallen ill with influenza/ARVI if the doctor identifies the&#xD;
      following symptoms: febrile/subfebrile body temperature, presence at least one flu-like&#xD;
      nonspecific symptom (decreased activity/impaired behavior/weakness; headache; chills) and at&#xD;
      least one respiratory symptom (runny nose; nasal stuffiness; hoarseness/husky voice; sore&#xD;
      throat; cough). In this case, the doctor makes an unscheduled visit (at home or in a medical&#xD;
      center), which is final. During the visit, the doctor carries out the procedures of Visit 4.&#xD;
      A nasopharyngeal swab is taken to identify the most common pathogens of influenza/ARVI.&#xD;
&#xD;
      If ARVI/influenza occurs within the first seven days from the onset of preventive therapy,&#xD;
      the disease will not be recorded as an adverse event and will not be taken into account to&#xD;
      evaluate the efficacy of the study drug, since an early manifestation of influenza/ARVI may&#xD;
      indicate that the participant was included in the study when he/she was in the incubation&#xD;
      period of an infectious disease.&#xD;
&#xD;
      During the study, concomitant therapy for underlying chronic conditions, as well as routine&#xD;
      vaccination of the participant, are allowed, with the exception of the drugs indicated in the&#xD;
      section &quot;Prohibited Concomitant Treatment&quot;.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 3, 2017</start_date>
  <completion_date type="Actual">May 20, 2019</completion_date>
  <primary_completion_date type="Actual">May 20, 2019</primary_completion_date>
  <phase>Phase 4</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time From Taking the First Dose of the Study Drug to the Onset of Influenza/ARVI Symptoms.</measure>
    <time_frame>in 12 weeks of the treatment</time_frame>
    <description>Based on medical records.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Children Not Falling Ill With Influenza or Another ARVI.</measure>
    <time_frame>in 12 weeks of the treatment</time_frame>
    <description>Based on medical records. Influenza/ARVI criteria are the following: febrile/subfebrile body temperature, presence at least one flu-like nonspecific symptom (decreased activity/weakness, headache, and chills), and at least one respiratory symptom (runny nose, nasal stuffiness, hoarseness/husky voice, sore throat, and cough).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Children With the Symptoms Requiring Antibacterial Therapy.</measure>
    <time_frame>in 12 weeks of the treatment</time_frame>
    <description>Based on medical records. Percentage of children with the symptoms of a respiratory or ear-nose-throat bacterial infection requiring antibacterial therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Children Requiring Hospitalized for Influenza/ARVI.</measure>
    <time_frame>in 12 weeks of the treatment</time_frame>
    <description>Based on medical records. Percentage of children hospitalized for influenza/ARVI or their complications.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence and Type of Adverse Events (AE).</measure>
    <time_frame>in 12 weeks of the treatment</time_frame>
    <description>Based on medical records. Presence and type of adverse events, their severity, relation to investigational drug, outcomes.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1036</enrollment>
  <condition>Preventive Medicine</condition>
  <arm_group>
    <arm_group_label>Anaferon for children</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet for oral use. One tablet per intake, once daily (approximately at the same time).&#xD;
The product is administered outside a meal (in the interval between meals or 15 min prior to meal or fluid intake), the tablets should be held in mouth until complete dissolution. For young children (aged 1 month to 3 years old), the tablet is recommended to be dissolved in a small amount (1 tablespoon) of drinking water of room temperature.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Tablet for oral use. Placebo using Anaferon for children scheme.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anaferon for children</intervention_name>
    <description>Tablet for oral use.</description>
    <arm_group_label>Anaferon for children</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Tablet for oral use.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Children of either gender aged from 1 month to 6 years old.&#xD;
&#xD;
          2. The absence of clinical symptoms of any infectious disease, but not earlier than 14&#xD;
             days from its onset.&#xD;
&#xD;
          3. Seasonal rise in ARVI incidence, confirmed by official information.&#xD;
&#xD;
          4. An information sheet (Informed Consent form) for the subject participation in the&#xD;
             clinical trial signed by one parent/adopter of the patient.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Acute or subacute period of infectious disease of any etiology (viral, bacterial,&#xD;
             fungal, etc.) and localization (including upper and lower respiratory tract infection,&#xD;
             meningitis, sepsis, otitis media, urinary tract infection, intestinal infection,&#xD;
             etc.).&#xD;
&#xD;
          2. History of (verified previously) or current suspected conditions such as:&#xD;
&#xD;
               -  primary or secondary immunodeficiency;&#xD;
&#xD;
               -  bronchopulmonary dysplasia, primary ciliary dyskinesia, cystic fibrosis, other&#xD;
                  chronic pulmonary diseases;&#xD;
&#xD;
               -  malformations of the respiratory and ENT organs (ear, throat, mouth, tongue,&#xD;
                  larynx, trachea, neck and salivary and thyroid glands, etc.);&#xD;
&#xD;
               -  immunopathological diseases (including Marshall syndrome, Behсet's syndrome,&#xD;
                  Kawasaki disease, etc.);&#xD;
&#xD;
               -  hematological diseases (including agranulocytosis, leukemia);&#xD;
&#xD;
               -  oncologic conditions.&#xD;
&#xD;
          3. Exacerbated or decompensated of chronic diseases affecting the patienrt's ability to&#xD;
             participate in the clinical trial.&#xD;
&#xD;
          4. Malabsorption syndrome, including congenital or acquired lactase or another&#xD;
             disaccharide deficiency, galactosemia.&#xD;
&#xD;
          5. Allergy/intolerance to any component of the study drug.&#xD;
&#xD;
          6. Course administration of the drug products specified in the section 'Prohibited&#xD;
             concomitant medications' within 2 weeks prior to enrollment.&#xD;
&#xD;
          7. Children whose parents/adopter parents will fail to comply with the observation&#xD;
             requirements of the trial or with the intake regimen of the study drug, from the&#xD;
             investigator's point of view.&#xD;
&#xD;
          8. Participation in other clinical trials within 3 month prior to enrollment in the&#xD;
             study.&#xD;
&#xD;
          9. The patient's parent/adopter parent is a member of the research team of the&#xD;
             investigational site directly involved in the study or a close relative of an&#xD;
             investigator. Close relatives are defined as husband/wife, parents, children, brothers&#xD;
             (sisters) regardless of whether they are biological or adopted.&#xD;
&#xD;
         10. The patient's parent/adopter parent works for OOO &quot;NPF &quot;MATERIA MEDICA HOLDING&quot; (i.e.,&#xD;
             the company's employee, part-time employee under contract or appointed official in&#xD;
             charge of the trial, or their immediate family).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Month</minimum_age>
    <maximum_age>6 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Municipal Autonomous Institution &quot;Children's City Clinical Hospital No. 11&quot;</name>
      <address>
        <city>Ekaterinburg</city>
        <zip>620028</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional budgetary health care institution &quot;Regional Children's Clinical Hospital&quot;</name>
      <address>
        <city>Ivanovo</city>
        <zip>153040</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Republican Children's Clinical Hospital of the Ministry of Health of the Udmurt Republic</name>
      <address>
        <city>Izhevsk</city>
        <zip>426009</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Educational Institution of Higher Education &quot;Kazan Medical University&quot; of the Ministry of Healthcare of the Russian Federation</name>
      <address>
        <city>Kazan</city>
        <zip>420012</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kazan Federal University</name>
      <address>
        <city>Kazan</city>
        <zip>420012</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal Budget Institution of Science &quot;Central Research Institute of Epidemiology&quot; of The Federal Service on Customers' Rights Protection and Human Well-being Surveillance</name>
      <address>
        <city>Moscow</city>
        <zip>111123</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Educational Institution of Higher Education &quot;Pirogov Russian National Research Medical University&quot; of the Ministry of Healthcare of the Russian Federation</name>
      <address>
        <city>Moscow</city>
        <zip>117997</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Federal-Funded Educational Institution of Higher Professional Training I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation</name>
      <address>
        <city>Moscow</city>
        <zip>119991</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LLC Center for Vaccine Prevention &quot;DIAVAKS&quot;</name>
      <address>
        <city>Moscow</city>
        <zip>129515</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Limited Liability Company &quot;Gubernskiy lekar'&quot;</name>
      <address>
        <city>Murmansk</city>
        <zip>183038</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Limited Liability Company &quot;MDP-Medical Group&quot;</name>
      <address>
        <city>Odintsovo</city>
        <zip>143005</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Educational Institution of Higher Education &quot;Orenburg State Medical University&quot; of the Ministry of Healthcare of the Russian Federation</name>
      <address>
        <city>Orenburg</city>
        <zip>460000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Municipal Health Care Institution &quot;City Child Health Clinical Polyclinic №5&quot;</name>
      <address>
        <city>Perm</city>
        <zip>614066</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Municipal Budgetary Health Care Institutions &quot;Semashko City Hospital №1 Rostov-on-Don &quot;</name>
      <address>
        <city>Rostov-na-Donu</city>
        <zip>344000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Municipal budgetary health care institution &quot;Children's city polyclinic №4&quot;</name>
      <address>
        <city>Rostov-na-Donu</city>
        <zip>344065</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Petersburg State Budgetary Healthcare Institution &quot;Children's City Polyclinic No. 44&quot;</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>191144</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Petersburg State Budgetary Health Care Institution &quot;Сity Polyclinic №44&quot;</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>192212</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Educational Institution of Higher Education &quot;St. Petersburg State Pediatric Medical Academy&quot; of Ministry of Health of Russian Federation</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>194100</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Petersburg State Budgetary Healthcare Institution &quot;Children's City Polyclinic No. 35&quot;</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>196191</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Petersburg State Budgetary Healthcare Institution &quot;Children's City Hospital No. 22&quot;</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>196650</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samara Regional Children's Sanatorium &quot;Yunost'&quot;</name>
      <address>
        <city>Samara</city>
        <zip>443031</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Budgetary Institution of Health of the Samara Region &quot;Samara City Children's Clinical Hospital No. 1 named after N.N. Ivanova&quot;</name>
      <address>
        <city>Samara</city>
        <zip>443079</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Limited Liability Company &quot;DNA Research Center&quot;</name>
      <address>
        <city>Saratov</city>
        <zip>410005</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional State Autonomous Healthcare Institution &quot;Children's Hospital №1&quot;</name>
      <address>
        <city>Tomsk</city>
        <zip>634050</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siberian State Medical University</name>
      <address>
        <city>Tomsk</city>
        <zip>634050</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bashkir State Medical University</name>
      <address>
        <city>Ufa</city>
        <zip>450008</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Volgograd State Medical University/Departmental Clinical Hospital at Volgograd-1 Station of Russian Railways</name>
      <address>
        <city>Volgograd</city>
        <zip>400131</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Volgograd State Medical University/Volgograd Regional Clinical Hospital # 1</name>
      <address>
        <city>Volgograd</city>
        <zip>400131</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yaroslavl State Medical University/Children's Clinic # 5</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yaroslavl State Medical University/Clinical Hospital # 8 (Children's Clinic # 1)</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yaroslavl State Medical University/Department of Infectious Diseases, Epidemiology and Children's Diseases</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yaroslavl State Medical University/Regional Children's Clinical Hospital # 8 (Children's Clinic # 2)</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Family polyclinic № 6</name>
      <address>
        <city>Tashkent</city>
        <zip>100194</zip>
        <country>Uzbekistan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
    <country>Uzbekistan</country>
  </location_countries>
  <removed_countries>
    <country>Kazakhstan</country>
  </removed_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>September 29, 2017</study_first_submitted>
  <study_first_submitted_qc>September 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <results_first_submitted>April 23, 2020</results_first_submitted>
  <results_first_submitted_qc>April 23, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">May 6, 2020</results_first_posted>
  <last_update_submitted>April 23, 2020</last_update_submitted>
  <last_update_submitted_qc>April 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 23, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT03301155/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Anaferon for Children</title>
          <description>Tablet for oral use. One tablet per intake, once daily (approximately at the same time).&#xD;
The product is administered outside a meal (in the interval between meals or 15 min prior to meal or fluid intake), the tablets should be held in mouth until complete dissolution. For young children (aged 1 month to 3 years old), the tablet is recommended to be dissolved in a small amount (1 tablespoon) of drinking water of room temperature.&#xD;
Anaferon for children: Tablet for oral use.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Tablet for oral use. Placebo using Anaferon for children scheme.&#xD;
Placebo: Tablet for oral use.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="528"/>
                <participants group_id="P2" count="508"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="520"/>
                <participants group_id="P2" count="501"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Сompliance with exclusion criteria</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Anaferon for Children</title>
          <description>Tablet for oral use. One tablet per intake, once daily (approximately at the same time).&#xD;
The product is administered outside a meal (in the interval between meals or 15 min prior to meal or fluid intake), the tablets should be held in mouth until complete dissolution. For young children (aged 1 month to 3 years old), the tablet is recommended to be dissolved in a small amount (1 tablespoon) of drinking water of room temperature.&#xD;
Anaferon for children: Tablet for oral use.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Tablet for oral use. Placebo using Anaferon for children scheme.&#xD;
Placebo: Tablet for oral use.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="520"/>
            <count group_id="B2" value="501"/>
            <count group_id="B3" value="1021"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="520"/>
                    <count group_id="B2" value="501"/>
                    <count group_id="B3" value="1021"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="520"/>
                    <measurement group_id="B2" value="501"/>
                    <measurement group_id="B3" value="1021"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="520"/>
                    <count group_id="B2" value="501"/>
                    <count group_id="B3" value="1021"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.1" spread="1.7"/>
                    <measurement group_id="B2" value="3.1" spread="1.7"/>
                    <measurement group_id="B3" value="3.1" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="520"/>
                    <count group_id="B2" value="501"/>
                    <count group_id="B3" value="1021"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="263"/>
                    <measurement group_id="B2" value="244"/>
                    <measurement group_id="B3" value="507"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="257"/>
                    <measurement group_id="B2" value="257"/>
                    <measurement group_id="B3" value="514"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Uzbekistan</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="520"/>
                    <count group_id="B2" value="501"/>
                    <count group_id="B3" value="1021"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Russia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="520"/>
                    <count group_id="B2" value="501"/>
                    <count group_id="B3" value="1021"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="505"/>
                    <measurement group_id="B2" value="486"/>
                    <measurement group_id="B3" value="991"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Time From Taking the First Dose of the Study Drug to the Onset of Influenza/ARVI Symptoms.</title>
        <description>Based on medical records.</description>
        <time_frame>in 12 weeks of the treatment</time_frame>
        <population>Intention-to-treat (ITT)</population>
        <group_list>
          <group group_id="O1">
            <title>Anaferon for Children</title>
            <description>Tablet for oral use. One tablet per intake, once daily (approximately at the same time).&#xD;
The product is administered outside a meal (in the interval between meals or 15 min prior to meal or fluid intake), the tablets should be held in mouth until complete dissolution. For young children (aged 1 month to 3 years old), the tablet is recommended to be dissolved in a small amount (1 tablespoon) of drinking water of room temperature.&#xD;
Anaferon for children: Tablet for oral use.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Tablet for oral use. Placebo using Anaferon for children scheme.&#xD;
Placebo: Tablet for oral use.</description>
          </group>
        </group_list>
        <measure>
          <title>Time From Taking the First Dose of the Study Drug to the Onset of Influenza/ARVI Symptoms.</title>
          <description>Based on medical records.</description>
          <population>Intention-to-treat (ITT)</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="520"/>
                <count group_id="O2" value="501"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="428.8" lower_limit="351.0" upper_limit="523.8"/>
                    <measurement group_id="O2" value="275.8" lower_limit="232.7" upper_limit="326.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.001</p_value>
            <method>Regression, Logistic</method>
            <method_desc>Comparison performed on the regression parameters scale. Estimates for mean time obtained under assumption of exponentially distributed time-to-event.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>superiority margin for hazard ratio was prespecified as 0.846. Lower hazard is better thus the upper confidence limit of HR expected to be lesser than margin</non_inferiority_desc>
            <p_value>0.0218</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.645</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.496</ci_lower_limit>
            <ci_upper_limit>0.839</ci_upper_limit>
            <estimate_desc>Lower HR is better</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Children Not Falling Ill With Influenza or Another ARVI.</title>
        <description>Based on medical records. Influenza/ARVI criteria are the following: febrile/subfebrile body temperature, presence at least one flu-like nonspecific symptom (decreased activity/weakness, headache, and chills), and at least one respiratory symptom (runny nose, nasal stuffiness, hoarseness/husky voice, sore throat, and cough).</description>
        <time_frame>in 12 weeks of the treatment</time_frame>
        <population>Intention-to-treat (ITT)</population>
        <group_list>
          <group group_id="O1">
            <title>Anaferon for Children</title>
            <description>Tablet for oral use. One tablet per intake, once daily (approximately at the same time).&#xD;
The product is administered outside a meal (in the interval between meals or 15 min prior to meal or fluid intake), the tablets should be held in mouth until complete dissolution. For young children (aged 1 month to 3 years old), the tablet is recommended to be dissolved in a small amount (1 tablespoon) of drinking water of room temperature.&#xD;
Anaferon for children: Tablet for oral use.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Tablet for oral use. Placebo using Anaferon for children scheme.&#xD;
Placebo: Tablet for oral use.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Children Not Falling Ill With Influenza or Another ARVI.</title>
          <description>Based on medical records. Influenza/ARVI criteria are the following: febrile/subfebrile body temperature, presence at least one flu-like nonspecific symptom (decreased activity/weakness, headache, and chills), and at least one respiratory symptom (runny nose, nasal stuffiness, hoarseness/husky voice, sore throat, and cough).</description>
          <population>Intention-to-treat (ITT)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="520"/>
                <count group_id="O2" value="501"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>4 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="516"/>
                    <measurement group_id="O2" value="452"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="482"/>
                    <measurement group_id="O2" value="415"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="424"/>
                    <measurement group_id="O2" value="368"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison between groups on week 4</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0003</p_value>
            <p_value_desc>Adjusted with Holm method for multiple comparrisons</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison between groups on week 8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Adjusted with Holm method for multiple comparrisons</non_inferiority_desc>
            <p_value>0.0003</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison between groups on week 12</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0021</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Children With the Symptoms Requiring Antibacterial Therapy.</title>
        <description>Based on medical records. Percentage of children with the symptoms of a respiratory or ear-nose-throat bacterial infection requiring antibacterial therapy.</description>
        <time_frame>in 12 weeks of the treatment</time_frame>
        <population>Intention-to-treat (ITT)</population>
        <group_list>
          <group group_id="O1">
            <title>Anaferon for Children</title>
            <description>Tablet for oral use. One tablet per intake, once daily (approximately at the same time).&#xD;
The product is administered outside a meal (in the interval between meals or 15 min prior to meal or fluid intake), the tablets should be held in mouth until complete dissolution. For young children (aged 1 month to 3 years old), the tablet is recommended to be dissolved in a small amount (1 tablespoon) of drinking water of room temperature.&#xD;
Anaferon for children: Tablet for oral use.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Tablet for oral use. Placebo using Anaferon for children scheme.&#xD;
Placebo: Tablet for oral use.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Children With the Symptoms Requiring Antibacterial Therapy.</title>
          <description>Based on medical records. Percentage of children with the symptoms of a respiratory or ear-nose-throat bacterial infection requiring antibacterial therapy.</description>
          <population>Intention-to-treat (ITT)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="520"/>
                <count group_id="O2" value="501"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1372</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Children Requiring Hospitalized for Influenza/ARVI.</title>
        <description>Based on medical records. Percentage of children hospitalized for influenza/ARVI or their complications.</description>
        <time_frame>in 12 weeks of the treatment</time_frame>
        <population>Intention-to-treat (ITT)</population>
        <group_list>
          <group group_id="O1">
            <title>Anaferon for Children</title>
            <description>Tablet for oral use. One tablet per intake, once daily (approximately at the same time).&#xD;
The product is administered outside a meal (in the interval between meals or 15 min prior to meal or fluid intake), the tablets should be held in mouth until complete dissolution. For young children (aged 1 month to 3 years old), the tablet is recommended to be dissolved in a small amount (1 tablespoon) of drinking water of room temperature.&#xD;
Anaferon for children: Tablet for oral use.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Tablet for oral use. Placebo using Anaferon for children scheme.&#xD;
Placebo: Tablet for oral use.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Children Requiring Hospitalized for Influenza/ARVI.</title>
          <description>Based on medical records. Percentage of children hospitalized for influenza/ARVI or their complications.</description>
          <population>Intention-to-treat (ITT)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="528"/>
                <count group_id="O2" value="508"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.999</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Presence and Type of Adverse Events (AE).</title>
        <description>Based on medical records. Presence and type of adverse events, their severity, relation to investigational drug, outcomes.</description>
        <time_frame>in 12 weeks of the treatment</time_frame>
        <population>Intention-to-treat (ITT)</population>
        <group_list>
          <group group_id="O1">
            <title>Anaferon for Children</title>
            <description>Tablet for oral use. One tablet per intake, once daily (approximately at the same time).&#xD;
The product is administered outside a meal (in the interval between meals or 15 min prior to meal or fluid intake), the tablets should be held in mouth until complete dissolution. For young children (aged 1 month to 3 years old), the tablet is recommended to be dissolved in a small amount (1 tablespoon) of drinking water of room temperature.&#xD;
Anaferon for children: Tablet for oral use.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Tablet for oral use. Placebo using Anaferon for children scheme.&#xD;
Placebo: Tablet for oral use.</description>
          </group>
        </group_list>
        <measure>
          <title>Presence and Type of Adverse Events (AE).</title>
          <description>Based on medical records. Presence and type of adverse events, their severity, relation to investigational drug, outcomes.</description>
          <population>Intention-to-treat (ITT)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="528"/>
                <count group_id="O2" value="508"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mild severity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65"/>
                    <measurement group_id="O2" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate severity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.999</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse/Serious adverse events were registered during 12 weeks therapy.</time_frame>
      <desc>Safety evaluation was based on the data from all randomized subjects receiving at least one dose of the study drug (n=1036; Safety population).</desc>
      <group_list>
        <group group_id="E1">
          <title>Anaferon for Children</title>
          <description>Tablet for oral use. One tablet per intake, once daily (approximately at the same time).&#xD;
The product is administered outside a meal (in the interval between meals or 15 min prior to meal or fluid intake), the tablets should be held in mouth until complete dissolution. For young children (aged 1 month to 3 years old), the tablet is recommended to be dissolved in a small amount (1 tablespoon) of drinking water of room temperature.&#xD;
Anaferon for children: Tablet for oral use.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Tablet for oral use. Placebo using Anaferon for children scheme.&#xD;
Placebo: Tablet for oral use.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="508"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Partial cramps</sub_title>
                <description>Partial epilepsy</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="49" subjects_at_risk="528"/>
                <counts group_id="E2" subjects_affected="44" subjects_at_risk="508"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Aphthous ulcer</sub_title>
                <description>Aphthous stomatitis</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <description>Loose stool</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Intestinal dysfunction</sub_title>
                <description>Intestinal dysfunction</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Teething</sub_title>
                <description>Teething</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <description>Vomiting</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Functional dyspepsia</sub_title>
                <description>Functional dyspepsia</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Functional gastrointestinal pathology</sub_title>
                <description>Functional gastrointestinal pathology</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Enteritis</sub_title>
                <description>Enteritis</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <description>Fervescence</description>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Chicken pox</sub_title>
                <description>Chicken pox</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="528"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Respiratory viral infection</sub_title>
                <description>ARVI, rhinopharyngitis</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="528"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Gastroenteritis caused by norovirus</sub_title>
                <description>Gastroenteritis caused by norovirus</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Herpes on the lips</sub_title>
                <description>Herpes on the lips</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Purulent conjunctivitis</sub_title>
                <description>Purulent conjunctivitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Purulent rhinitis</sub_title>
                <description>Purulent rhinitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <description>Urinary tract infection</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Non-purulent otitis media</sub_title>
                <description>Non-purulent otitis media</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Obstructive bronchitis</sub_title>
                <description>Obstructive bronchitis</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Acute respiratory tract infection</sub_title>
                <description>Acute respiratory tract infection</description>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="528"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Acute nasopharyngitis</sub_title>
                <description>Acute nasopharyngitis</description>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="528"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Acute rhinitis</sub_title>
                <description>Acute rhinitis</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Acute tracheitis</sub_title>
                <description>Acute tracheitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Acute pharyngitis</sub_title>
                <description>Acute pharyngitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Otitis</sub_title>
                <description>Otitis</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Felon</sub_title>
                <description>Panaritium</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <description>Rhinitis</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Rhinosinusitis</sub_title>
                <description>Rhinosinusitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <description>Rhinopharyngitis</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Rotavirus infection</sub_title>
                <description>Rotavirus infection</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Viral otitis media</sub_title>
                <description>Viral otitis media</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Acute otitis media</sub_title>
                <description>Acute otitis media</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Pharyngotonsillitis</sub_title>
                <description>Pharyngotonsillitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Pharyngotracheitis</sub_title>
                <description>Pharyngotracheitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Foreign body aspiration</sub_title>
                <description>Aspiration of a foreign matter</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <description>Headache</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Partial epilepsy</sub_title>
                <description>Partial epilepsy</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Stuttering</sub_title>
                <description>Stammering</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Throat hyperemia</sub_title>
                <description>Throat hyperemia</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Runny nose</sub_title>
                <description>Runny nose</description>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="528"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <description>Nasal bleeding</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <description>Productive cough</description>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="528"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Dry cough</sub_title>
                <description>Dry cough</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rash</sub_title>
                <description>Allergic rash</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Allergic dermatitis</sub_title>
                <description>Allergic dermatitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Skin itch</sub_title>
                <description>Skin itch</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Acute allergic urticaria</sub_title>
                <description>Acute allergic urticaria</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="508"/>
              </event>
              <event>
                <sub_title>Facial rash</sub_title>
                <description>Rash on the skin of the face</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="528"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="508"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Michael Putilovskiy, MD, PhD, Clinical and Medical Department Director</name_or_title>
      <organization>Materia Medica Holding</organization>
      <phone>+74952761571 ext 302</phone>
      <email>PutilovskiyMA@materiamedica.ru</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03301155
org study id: MMH-AD-008
nct id: NCT03301155
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The objective of this study is to obtain additional data on the efficacy and safety of
      12-week course of therapy with Anaferon for children for prevention of influenza and other
      acute respiratory viral infections in children during the peaks of seasonal morbidity.
Design: an international, multicenter, double-blind, placebo-controlled, randomized study in
      parallel groups.

      The study will enroll children of either gender aged of 1 month to 6 years old. Children can
      participate in the study, regardless of the frequency of previous ARVI. A potential study
      participant should not be in the incubation (if known), prodromal, acute/subacute periods of
      any infectious disease (except for the recovery period). Schedule for enrollment of
      participants: during the period of a seasonal rise in influenza/ARVI incidence in the Russian
      Federation and the Republic of Uzbekistan. Screening and randomization of participants will
      be subject to availability of official information on the incidence of influenza/ARVI in the
      relevant study region.

      The doctor makes the first visit to the participant in the medical center or at home. After
      the parent/adoptive parent signs the information sheet (informed consent form), the doctor
      evaluates the possibility of the participant being included in the trial. If the child meets
      all the inclusion criteria and does not have all non-inclusion criteria, then he/she is
      included in the study, the doctor fills in Clinical Research Form. At visit 1 (Day 1), the
      participant is randomized into one of two groups: the 1st group participants will take
      Anaferon for children according to the preventive regimen for 12 weeks; the 2nd group
      participants will take Placebo according to the regimen of Anaferon for 12 weeks.

      In total, the study participant will be observed for 12 weeks (screening and randomization up
      to 1 day, preventive treatment for 12 weeks).

      During the observation period at 4 (Visit 2), 8 (Visit 3) and 12 (Visit 4) weeks, three
      visits are planned.

      Visits 2 (Week 4 ± 3 days) and 3 (Week 8 ± 3 days) are conducted in the form of a telephone
      survey of parents/adoptive parents about the participant's health status, presence/absence of
      symptoms of influenza/ARVI, possible use of antibacterial drugs and/or hospitalization during
      the course preventive therapy.

      Visit 4 (Week 12 ± 3 days) is carried out at home or in a medical center; the doctor collects
      complaints, examines the participant, registers concomitant therapy, assesses the compliance
      of the therapy.

      If in the period from 2 to 12 weeks a participant falls ill with influenza/ARVI, then he/she
      prematurely completes participation in the study (as having reached the primary endpoint). A
      participant is considered fallen ill with influenza/ARVI if the doctor identifies the
      following symptoms: febrile/subfebrile body temperature, presence at least one flu-like
      nonspecific symptom (decreased activity/impaired behavior/weakness; headache; chills) and at
      least one respiratory symptom (runny nose; nasal stuffiness; hoarseness/husky voice; sore
      throat; cough). In this case, the doctor makes an unscheduled visit (at home or in a medical
      center), which is final. During the visit, the doctor carries out the procedures of Visit 4.
      A nasopharyngeal swab is taken to identify the most common pathogens of influenza/ARVI.

      If ARVI/influenza occurs within the first seven days from the onset of preventive therapy,
      the disease will not be recorded as an adverse event and will not be taken into account to
      evaluate the efficacy of the study drug, since an early manifestation of influenza/ARVI may
      indicate that the participant was included in the study when he/she was in the incubation
      period of an infectious disease.

      During the study, concomitant therapy for underlying chronic conditions, as well as routine
      vaccination of the participant, are allowed, with the exception of the drugs indicated in the
      section "Prohibited Concomitant Treatment".
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time From Taking the First Dose of the Study Drug to the Onset of Influenza/ARVI Symptoms.
time frame: in 12 weeks of the treatment
description: Based on medical records.
measure: Percentage of Children Not Falling Ill With Influenza or Another ARVI.
time frame: in 12 weeks of the treatment
description: Based on medical records. Influenza/ARVI criteria are the following: febrile/subfebrile body temperature, presence at least one flu-like nonspecific symptom (decreased activity/weakness, headache, and chills), and at least one respiratory symptom (runny nose, nasal stuffiness, hoarseness/husky voice, sore throat, and cough).
measure: Percentage of Children With the Symptoms Requiring Antibacterial Therapy.
time frame: in 12 weeks of the treatment
description: Based on medical records. Percentage of children with the symptoms of a respiratory or ear-nose-throat bacterial infection requiring antibacterial therapy.
measure: Percentage of Children Requiring Hospitalized for Influenza/ARVI.
time frame: in 12 weeks of the treatment
description: Based on medical records. Percentage of children hospitalized for influenza/ARVI or their complications.
measure: Presence and Type of Adverse Events (AE).
time frame: in 12 weeks of the treatment
description: Based on medical records. Presence and type of adverse events, their severity, relation to investigational drug, outcomes.
arm group label: Anaferon for children
arm group type: Experimental
description: Tablet for oral use. One tablet per intake, once daily (approximately at the same time).
The product is administered outside a meal (in the interval between meals or 15 min prior to meal or fluid intake), the tablets should be held in mouth until complete dissolution. For young children (aged 1 month to 3 years old), the tablet is recommended to be dissolved in a small amount (1 tablespoon) of drinking water of room temperature.
arm group label: Placebo
arm group type: Placebo Comparator
description: Tablet for oral use. Placebo using Anaferon for children scheme.
intervention type: Drug
intervention name: Anaferon for children
description: Tablet for oral use.
arm group label: Anaferon for children
intervention type: Drug
intervention name: Placebo
description: Tablet for oral use.
arm group label: Placebo
criteria: 
gender: All
minimum age: 1 Month
maximum age: 6 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
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country: Russian Federation
country: Uzbekistan
country: Kazakhstan
responsible party type: Sponsor
mesh term: Influenza, Human
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 