<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/NCT04425460</url>
  </required_header>
  <id_info>
    <org_study_id>HS216C17(MRCT)</org_study_id>
    <nct_id>NCT04425460</nct_id>
  </id_info>
  <brief_title>A Multi-center,Randomized,Double-blind,Placebo-controlled,Phase 3 Study Evaluating Favipiravir in Treatment of COVID19</brief_title>
  <official_title>A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase III Clinical Study Evaluating the Efficacy and Safety of Favipiravir in the Treatment of Adult Patients With COVID-19-Moderate Type</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhejiang Hisun Pharmaceutical Co. Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Opera CRO, a TIGERMED Group Company</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Zhejiang Hisun Pharmaceutical Co. Ltd.</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>
      This is a multi-center, randomized, double-blind, placebo-controlled, phase III clinical&#xD;
      study to evaluate the efficacy of Favipiravir combined with supportive care for adult&#xD;
      patients with COVID-19-Moderate type.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 2020</start_date>
  <completion_date type="Anticipated">September 2020</completion_date>
  <primary_completion_date type="Anticipated">August 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>
    <intervention_model_description>This is a multi-center, randomized, double-blind, placebo-controlled (1:1) clinical study to explore the efficacy and safety of Favipiravir</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time from randomization to clinical recovery</measure>
    <time_frame>28 days</time_frame>
    <description>The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory rate and SPO2 and relief of cough (where there are relevant abnormal symptoms at enrolment) that is maintained for at least 72h.&#xD;
Criteria for normalization or relief:&#xD;
Pyrexia (body temperature): axillary ≤37℃，or oral≤37.5℃，or rectal or tympanic&#xD;
≤38℃;&#xD;
Respiratory rate: ≤24/min without oxygen inhalation;&#xD;
SPO2: &gt;94% without oxygen inhalation;&#xD;
Cough: Subject-perceived improvement or resolution of cough.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Negativity in RT-PCR nucleic acid test</measure>
    <time_frame>28 days</time_frame>
    <description>Time from randomization to negativity in RT-PCR nucleic acid test for 2019-nCov within 28 days of randomization;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from randomization to resolution of pyrexia</measure>
    <time_frame>28 days</time_frame>
    <description>Time from randomization to resolution of pyrexia (defined the same as for the primary efficacy variable; applicable to subjects with pyrexia at enrolment) within 28 days of randomization;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from randomization to relief of cough</measure>
    <time_frame>28 days</time_frame>
    <description>Time from randomization to relief of cough (defined the same as for the primary efficacy variable; applicable to subjects with cough at enrolment) within 28 days of randomization;&#xD;
It is recommended that the severity of cough be graded as per NCI-CTCAE v5.0:&#xD;
Mild: Requires non-prescription treatment;&#xD;
Moderate: Requires medication treatment; limits instrumental activities of daily living;&#xD;
Severe: Limits self-care activities of daily living;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of deterioration/aggravation of pneumonia</measure>
    <time_frame>28 days</time_frame>
    <description>Incidence of deterioration/aggravation of pneumonia (defined as SPO2≤93% or PaO2/FiO2 ≤300 mmHg or distressed RR≥30/min without oxygen inhalation and requiring oxygen therapy or more advanced breath support) within 28 days of randomization;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from randomization to relief of dyspnoea</measure>
    <time_frame>28 days</time_frame>
    <description>Time from randomization to relief of dyspnoea (defined as subject-perceived improvement or resolution of dyspnoea; applicable to subjects with dyspnoea at enrolment) within 28 days of randomization;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of auxiliary oxygen therapy or non-invasive ventilation</measure>
    <time_frame>28 days</time_frame>
    <description>Rate of auxiliary oxygen therapy or non-invasive ventilation within 28 days of randomization;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU admission rate within 28 days of randomization</measure>
    <time_frame>28 days</time_frame>
    <description>ICU admission rate within 28 days of randomization (except patients already enrolled in ICU which respect eligibility criteria);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality within 28 days of randomization.</measure>
    <time_frame>28 days</time_frame>
    <description>All-cause mortality within 28 days of randomization.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">256</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Favipiravir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Favipiravir Tablets, 200 mg/tablet Favipiravir combined with supportive care recommended in the current National/Local guidelines. Favipiravir dosage and method of administration: Day 1: 1800mg, BID; Day 2 and thereafter: 600mg, TID, for a maximum of 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo control group Favipiravir combined with supportive care recommended in the current National/Local guidelines</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Favipiravir</intervention_name>
    <description>Favipiravir combined with supportive care recommended in the current National/Local guidelines. Favipiravir dosage and method of administration: Day 1 1800 mg x2; Day 2 up to a maximum of 14 days 600 mg x 3</description>
    <arm_group_label>Favipiravir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo combined with supportive care recommended in the current National/Local guidelines. Placebo dosage and method of administration: Day 1 1800 mg x2; Day 2 up to a maximum of 14 days 600 mg x 3</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Voluntarily participating in the clinical study; fully understanding and being fully&#xD;
             informed of the study and having signed the Informed Consent Form (ICF); willingness&#xD;
             and capability to complete all the study procedures;&#xD;
&#xD;
          2. Age 18-75 years (inclusive) at the time of signing ICF;&#xD;
&#xD;
          3. Being confirmed with COVID-19-Moderate type according to Competent Authority and&#xD;
             Ministry of Health and respective country guidelines and recommendations reported in&#xD;
             Appendix 1 (a, b, c, d) to the present protocol. Based on comprehensive analysis and&#xD;
             judgement taking into account both the epidemiological history and clinical&#xD;
             manifestations, the diagnosis is to be confirmed for suspected cases or suspected&#xD;
             cases/clinically diagnosed cases with all of the following etiological evidences:&#xD;
&#xD;
               -  Positivity in RT-PCR 2019-nCov test on respiratory tract specimens;&#xD;
&#xD;
               -  High homology with known gene sequence of 2019-nCov in viral gene sequencing on&#xD;
                  respiratory tract specimens.&#xD;
&#xD;
          4. Chest imaging (CT as first option or X-ray if CT not possible)-documented pneumonia;&#xD;
             if CT cannot be performed, Pneumonia confirmed by X-ray may be used. The method of&#xD;
             chest imaging pneumonia diagnosis must be consistent all through the study period;&#xD;
&#xD;
          5. Patients with pyrexia (axillary ≥37℃ or oral ≥ 37.5℃, or tympanic or rectal≥38℃) or&#xD;
             either respiratory rate &gt;24/min and &lt;30/min or cough; For not hospitalized patients,&#xD;
             the Investigator should maintain the detection method consistent through study period.&#xD;
             In addition, the Investigator should maintain the data collection and quality&#xD;
             compliant with GCP requirements.&#xD;
&#xD;
          6. The interval between symptoms onset and randomization is no more than 10 days;&#xD;
             symptoms onset is primarily based on pyrexia, and can be based on cough or other&#xD;
             related symptoms for patients without experiencing pyrexia following onset (it is&#xD;
             strongly recommended that the interval between symptoms onset and randomization should&#xD;
             not exceed 5 days);&#xD;
&#xD;
          7. For female subjects: evidence of post-menopause, or, for pre-menopause subjects,&#xD;
             negative pre-treatment serum or urine pregnancy test. Menopause is defined as&#xD;
             amenorrhea for at least 12 months without other medical cause, with the following&#xD;
             age-specific requirements:&#xD;
&#xD;
               -  For female subjects aged &lt;50 years: menopause for at least 12 months following&#xD;
                  withdrawal of exogenous hormonal therapy, with LH or FSH within the&#xD;
                  post-menopausal ranges, or having undergone any contraceptive surgery (bilateral&#xD;
                  oophorectomy or hysterectomy);&#xD;
&#xD;
               -  For female subjects aged ≥ 50 years: menopause for at least 12 months following&#xD;
                  withdrawal of exogenous hormonal therapy, or having undergone&#xD;
                  radiotherapy-induced oophorectomy with amenorrhea &gt;1 year, or having undergone&#xD;
                  chemotherapy-induced menopause with amenorrhea&gt;1 year, or having undergone any&#xD;
                  contraceptive surgery (bilateral oophorectomy or hysterectomy).&#xD;
&#xD;
          8. Eligible subjects of child-bearing age (male or female) must agree to take effective&#xD;
             contraceptive measures (including hormonal contraception, barrier methods or&#xD;
             abstinence) with his/her partner during the study period and for at least 3 months (in&#xD;
             male) and 1 month (in female)following the last study treatment; in addition:&#xD;
&#xD;
               1. For female participants of childbearing potential only highly effective methods&#xD;
                  (failure rate &lt; 1 %) plus one barrier method is allowed throughout the period of&#xD;
                  relevant systemic exposure with Favipiravir. Double barrier methods alone are not&#xD;
                  considered as highly effective. Additionally, pregnancy testing at baseline only&#xD;
                  is not deemed sufficient and must be repeated more frequently, at least if&#xD;
                  clinical signs of pregnancy occur and at follow-up / end of study.&#xD;
&#xD;
               2. male participants, if vasectomized or not, must wear a condom each time having&#xD;
                  heterosexual intercourse throughout the period of relevant systemic exposure with&#xD;
                  Favipiravir (as it is distributed to seminal fluid).&#xD;
&#xD;
               3. male participant must be instructed not to have intercourse with pregnant women&#xD;
                  throughout the period of relevant systemic exposure with Favipiravir.&#xD;
&#xD;
               4. For further details on contraception in clinical trials, please refer to the CTFG&#xD;
                  guidance: https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-&#xD;
                  About_HMA/Working_Groups/CTFG/2014_09_HM A_CTFG_Contraception.pd&#xD;
&#xD;
          9. Not participating in any other drug clinical studies before completion of the present&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Where, in the opinion of the investigator, participation in this study will not be in&#xD;
             the best interest of the subject, or any other circumstances that prevent the subject&#xD;
             from participating in the study safely;&#xD;
&#xD;
          2. Refractory nausea, vomiting, or chronic gastrointestinal disorders, inability to&#xD;
             swallow the study drug or having undergone extensive bowel resection which may affect&#xD;
             adequate absorption of Favipiravir;&#xD;
&#xD;
          3. Severe liver disease: underlying liver cirrhosis or alanine aminotransferase&#xD;
             (ALT)/aspartate aminotransferase (AST) elevated over 5 times the ULN;&#xD;
&#xD;
          4. Gout/history of gout or hyperuricemia (above the ULN);&#xD;
&#xD;
          5. Oxygen saturation (SPO2) ≤93% or arterial oxygen partial pressure (PaO2)/ fraction of&#xD;
             inspired O2 (FiO2) ≤300 mmHg;&#xD;
&#xD;
          6. Known allergy or hypersensitivity to Favipiravir or any of its excipients, or to&#xD;
             placebo excipients&#xD;
&#xD;
          7. Known severe renal impairment [creatinine clearance (CrCl) &lt;30 mL/min] or having&#xD;
             received continuous renal replacement therapy, hemodialysis or peritoneal dialysis;&#xD;
&#xD;
          8. Possibility of the subject being transferred to a non-study hospital within 72h;&#xD;
&#xD;
          9. Pregnant or lactating women;&#xD;
&#xD;
         10. Having used Favipiravir or participated in any other interventional drug clinical&#xD;
             study within 30 days prior to first dose of study drug or having received treatments&#xD;
             with other Investigational Medicinal Products (IMPs) or previous therapies within two&#xD;
             weeks or five times the half-life of the drug, whichever is longer, must lead to&#xD;
             exclusion&#xD;
&#xD;
         11. Persons, who were placed in an institution due to official or legal orders should be&#xD;
             excluded&#xD;
&#xD;
         12. Persons, who are dependent on the sponsor, the investigator or the trial site, meaning&#xD;
             that the voluntary nature of their consent is no longer guaranteed, must be excluded&#xD;
             from participation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Dionisio Barattini, MD Europe, Opera CRO</last_name>
    <phone>+40774012684</phone>
    <email>barattini@operacro.ro</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Emanuel Dogaru, CPM, Opera CRO</last_name>
    <phone>+40724345115</phone>
    <email>dogaru@operacro.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Zhejiang University School of Medicine</name>
      <address>
        <city>Hangzhou</city>
        <state>Shangcheng District</state>
        <zip>310003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking University First Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Xicheng District</state>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Internal Medicine Pneumology and infectious diseases Neukölln Clinic</name>
      <address>
        <city>Berlin</city>
        <zip>12351</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical clinic and polyclinic IV Hospital of the University of Munich</name>
      <address>
        <city>München</city>
        <zip>80336</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Infectious Diseases Hospital Cluj-Napoca</name>
      <address>
        <city>Cluj-Napoca</city>
        <state>Cluj</state>
        <zip>400000</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Institute of Infectious Diseases &quot;Prof.Dr.Matei Bals&quot;</name>
      <address>
        <city>Bucharest</city>
        <state>Ilfov</state>
        <zip>'021105</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;Dr.Victor Babes&quot; Infectious Diseases and Pneumoftiziology Clinical Hospital Timisoara</name>
      <address>
        <city>Timisoara</city>
        <state>Timis</state>
        <zip>'300310</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;Dr.Victor Babes&quot; Infectious Diseases and Pneumoftiziology Clinical Hospital Timisoara</name>
      <address>
        <city>Timişoara</city>
        <state>Timis</state>
        <zip>300310</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dr.Victor Babes Infectious Diseases and Pneumoftiziology Clinical Hospital Timisoara</name>
      <address>
        <city>Timişoara</city>
        <state>Timis</state>
        <zip>300310</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emergency County Hospital &quot;Pius Brinzeu&quot;Timisoara</name>
      <address>
        <city>Timişoara</city>
        <state>Timis</state>
        <zip>300723</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
    <country>Germany</country>
    <country>Romania</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 9, 2020</last_update_submitted>
  <last_update_submitted_qc>June 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 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>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Favipiravir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04425460
org study id: HS216C17(MRCT)
nct id: NCT04425460
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This is a multi-center, randomized, double-blind, placebo-controlled, phase III clinical
      study to evaluate the efficacy of Favipiravir combined with supportive care for adult
      patients with COVID-19-Moderate type.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a multi-center, randomized, double-blind, placebo-controlled (1:1) clinical study to explore the efficacy and safety of Favipiravir
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Time from randomization to clinical recovery
time frame: 28 days
description: The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory rate and SPO2 and relief of cough (where there are relevant abnormal symptoms at enrolment) that is maintained for at least 72h.
Criteria for normalization or relief:
Pyrexia (body temperature): axillary ≤37℃，or oral≤37.5℃，or rectal or tympanic
≤38℃;
Respiratory rate: ≤24/min without oxygen inhalation;
SPO2: >94% without oxygen inhalation;
Cough: Subject-perceived improvement or resolution of cough.
measure: Negativity in RT-PCR nucleic acid test
time frame: 28 days
description: Time from randomization to negativity in RT-PCR nucleic acid test for 2019-nCov within 28 days of randomization;
measure: Time from randomization to resolution of pyrexia
time frame: 28 days
description: Time from randomization to resolution of pyrexia (defined the same as for the primary efficacy variable; applicable to subjects with pyrexia at enrolment) within 28 days of randomization;
measure: Time from randomization to relief of cough
time frame: 28 days
description: Time from randomization to relief of cough (defined the same as for the primary efficacy variable; applicable to subjects with cough at enrolment) within 28 days of randomization;
It is recommended that the severity of cough be graded as per NCI-CTCAE v5.0:
Mild: Requires non-prescription treatment;
Moderate: Requires medication treatment; limits instrumental activities of daily living;
Severe: Limits self-care activities of daily living;
measure: Incidence of deterioration/aggravation of pneumonia
time frame: 28 days
description: Incidence of deterioration/aggravation of pneumonia (defined as SPO2≤93% or PaO2/FiO2 ≤300 mmHg or distressed RR≥30/min without oxygen inhalation and requiring oxygen therapy or more advanced breath support) within 28 days of randomization;
measure: Time from randomization to relief of dyspnoea
time frame: 28 days
description: Time from randomization to relief of dyspnoea (defined as subject-perceived improvement or resolution of dyspnoea; applicable to subjects with dyspnoea at enrolment) within 28 days of randomization;
measure: Rate of auxiliary oxygen therapy or non-invasive ventilation
time frame: 28 days
description: Rate of auxiliary oxygen therapy or non-invasive ventilation within 28 days of randomization;
measure: ICU admission rate within 28 days of randomization
time frame: 28 days
description: ICU admission rate within 28 days of randomization (except patients already enrolled in ICU which respect eligibility criteria);
measure: All-cause mortality within 28 days of randomization.
time frame: 28 days
description: All-cause mortality within 28 days of randomization.
arm group label: Favipiravir
arm group type: Experimental
description: Favipiravir Tablets, 200 mg/tablet Favipiravir combined with supportive care recommended in the current National/Local guidelines. Favipiravir dosage and method of administration: Day 1: 1800mg, BID; Day 2 and thereafter: 600mg, TID, for a maximum of 14 days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo control group Favipiravir combined with supportive care recommended in the current National/Local guidelines
intervention type: Drug
intervention name: Favipiravir
description: Favipiravir combined with supportive care recommended in the current National/Local guidelines. Favipiravir dosage and method of administration: Day 1 1800 mg x2; Day 2 up to a maximum of 14 days 600 mg x 3
arm group label: Favipiravir
intervention type: Other
intervention name: Placebo
description: Placebo combined with supportive care recommended in the current National/Local guidelines. Placebo dosage and method of administration: Day 1 1800 mg x2; Day 2 up to a maximum of 14 days 600 mg x 3
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Dionisio Barattini, MD Europe, Opera CRO
phone: +40774012684
email: barattini@operacro.ro
last name: Emanuel Dogaru, CPM, Opera CRO
phone: +40724345115
email: dogaru@operacro.com
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
country: Germany
country: Romania
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Favipiravir
sharing ipd: Undecided