<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/NCT03777163</url>
  </required_header>
  <id_info>
    <org_study_id>FLU-07-IB</org_study_id>
    <nct_id>NCT03777163</nct_id>
  </id_info>
  <brief_title>Safety and Immunogenicity of the Butantan Institute Influenza Vaccine Compared to Sanofi Pasteur Influenza Vaccine</brief_title>
  <official_title>Safety and Immunogenicity of the Butantan Institute Trivalent Seasonal Influenza Vaccine in Comparison With the Sanofi Pasteur Trivalent Seasonal Influenza Vaccine in Brazilian Subjects.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Butantan Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Butantan Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall aim of this study is to evaluate the safety and immunogenicity of Butantan&#xD;
      Institute Trivalent Seasonal Influenza Vaccine in comparison with the Sanofi Trivalent&#xD;
      Seasonal Influenza Vaccine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To detemine whether immunogenicity elicited by a single-dose Butantan Institute Trivalent&#xD;
      Seasonal Influenza Vaccine is not inferior to that elicited by a single dose of Sanofi&#xD;
      Trivalent Seasonal Influenza Vaccine in adult and elderly populations measured by HI GMT for&#xD;
      the three vaccine components 21 days post-immunization.&#xD;
&#xD;
      To describe the safety profile of Butantan Institute Trivalent Seasonal Influenza Vaccine and&#xD;
      Sanofi Trivalent Seasonal Influenza Vaccine after a single dose in adult and elderly&#xD;
      populations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">April 22, 2019</start_date>
  <completion_date type="Anticipated">March 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">January 15, 2020</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>Geometric Mean Titers of Hemaglutination Inhibition (HI) for each of the three vaccine components.</measure>
    <time_frame>21 days</time_frame>
    <description>HI titers will be determined in serum samples collected before vaccination and 21 days after vaccination from all the subjects.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse events occurring over the immediate 30-minute post vaccination</measure>
    <time_frame>30-minute post vaccination</time_frame>
    <description>Immediate Reactogenicity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with solicited local AE (erythema, swelling, induration, pain, tenderness, ecchymosis, pruritus) until 3 days post vaccination.</measure>
    <time_frame>3 days post vaccination</time_frame>
    <description>Solicited Local Adverse Events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with solicited systemic AEs (fever, fatigue, malaise, myalgia, arthralgia, chills, nausea, vomiting, and headache) until 3 days post vaccination.</measure>
    <time_frame>3 days post vaccination</time_frame>
    <description>Solicited Systemic Adverse Events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with unsolicited adverse events up to 3 days after vaccination.</measure>
    <time_frame>3 days after vaccination.</time_frame>
    <description>Unsolicited Adverse Events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>All adverse reactions with severity graded 3/4 over the entire study period.</measure>
    <time_frame>180 days after vaccination.</time_frame>
    <description>Adverse Reactions with severity graded 3/4</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">632</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>Butantan Trivalent Influenza Vaccine</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Butantan Institute Trivalent Seasonal Influenza Vaccine (IB-TIV): 15 μg influenza A/H1N1 antigen + 15 μg influenza A/H3N2 antigen + 15 μg influenza B antigen&#xD;
Patients will receive one dose (0,5 ml) via intramuscular injection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sanofi Trivalent Influenza Vaccine</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Sanofi Trivalent Seasonal Influenza Vaccine (IB-TIV): 15 μg influenza A/H1N1 antigen + 15 μg influenza A/H3N2 antigen + 15 μg influenza B antigen&#xD;
Patients will receive one dose (0,5 ml) via intramuscular injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Butantan Institute Trivalent Seasonal Influenza Vaccine</intervention_name>
    <description>Butantan Institute and Pasteur-Mérieux (present, Sanofi Pasteur) established a technology transfer in 1999 for the production of a trivalent influenza vaccine of inactivated split-virion using embryonated eggs. The technology transfer followed a progressive approach from importing the finished product, to packaging and quality control test for release (1999), and, finally, to the first batch of influenza vaccine entirely produced by Butantan (2011). In 2013, the Butantan vaccine was registered by the Brazilian National Agency of Sanitary Surveillance (ANVISA).</description>
    <arm_group_label>Butantan Trivalent Influenza Vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Sanofi Trivalent Seasonal Influenza Vaccine</intervention_name>
    <description>VAXIGRIP® was launched in 1968 and since then has been licensed in more than 100 countries and prequalified by WHO in 2011. Several clinical studies by Sanofi Pasteur have examined the safety and immunogenicity of Vaxigrip® in older children (8-10 years), adults (18-59 years), elderly (&gt; 60 years),11,12 children (six months to three years) 13 and pregnant women.</description>
    <arm_group_label>Sanofi Trivalent Influenza Vaccine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult, male or female, age 18 to 69 years (inclusive) at the time of enrollment;&#xD;
&#xD;
          -  Provide written informed consent;&#xD;
&#xD;
          -  Agrees to complete all study visits, procedures and contacts;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic medical conditions such as psychiatric conditions, diabetes, hypertension or&#xD;
             any other conditions that might place the subjects at high risk of adverse events.&#xD;
             Study clinicians will use clinical judgment on a case-by-case basis to assess safety&#xD;
             risks under this criterion;&#xD;
&#xD;
          -  Clinically significant abnormalities on physical examination;&#xD;
&#xD;
          -  Use of immunosuppressive medications such as systemic corticosteroids or&#xD;
             chemotherapeutics, or immunosuppressive illness. It will be considered&#xD;
             immunosuppressive dose of systemic corticosteroids the equivalent to a dose ≥10 mg of&#xD;
             prednisone per day for over 14 days;&#xD;
&#xD;
          -  Women who report being pregnant or have plans to become pregnant during the study&#xD;
             period;&#xD;
&#xD;
          -  Participation in research involving another investigational product within 30 days&#xD;
             before planned date of first vaccination or anytime through the last study safety&#xD;
             visit;&#xD;
&#xD;
          -  Acute febrile illness (axilar temperature ≥ 37.8°C);&#xD;
&#xD;
          -  Hypersensitivity to egg or chicken proteins;&#xD;
&#xD;
          -  History of Guillain-Barre Syndrome;&#xD;
&#xD;
          -  Thrombocytopenia or a bleeding disorder contraindicating intramuscular vaccination;&#xD;
&#xD;
          -  Unstable chronic illness (defined as illness requiring hospitalization or a clinically&#xD;
             significant change in medication in the previous 12 weeks);&#xD;
&#xD;
          -  Alcohol abuse or drug addiction;&#xD;
&#xD;
          -  Any vaccination within the previous 4 weeks;&#xD;
&#xD;
          -  Seasonal influenza vaccination in the previous 6 months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>69 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexander Precioso, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Instituto butantan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Unidade de Pesquisa Clínica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo</name>
      <address>
        <city>Ribeirão Preto</city>
        <state>SP</state>
        <zip>14049900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Referências para Imunobiológicos Especiais da Universidade Federal de São Paulo</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>01220200</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Pesquisas Clínicas do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>05403 000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Referência de Imunobiológicos Especiais (CRIE) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>05403-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>July 11, 2019</last_update_submitted>
  <last_update_submitted_qc>July 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vaccine</keyword>
  <keyword>Immunization</keyword>
  <keyword>Safety</keyword>
  <keyword>Immunogenicity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</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/NCT03777163
org study id: FLU-07-IB
nct id: NCT03777163
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The overall aim of this study is to evaluate the safety and immunogenicity of Butantan
      Institute Trivalent Seasonal Influenza Vaccine in comparison with the Sanofi Trivalent
      Seasonal Influenza Vaccine.
To detemine whether immunogenicity elicited by a single-dose Butantan Institute Trivalent
      Seasonal Influenza Vaccine is not inferior to that elicited by a single dose of Sanofi
      Trivalent Seasonal Influenza Vaccine in adult and elderly populations measured by HI GMT for
      the three vaccine components 21 days post-immunization.

      To describe the safety profile of Butantan Institute Trivalent Seasonal Influenza Vaccine and
      Sanofi Trivalent Seasonal Influenza Vaccine after a single dose in adult and elderly
      populations.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Geometric Mean Titers of Hemaglutination Inhibition (HI) for each of the three vaccine components.
time frame: 21 days
description: HI titers will be determined in serum samples collected before vaccination and 21 days after vaccination from all the subjects.
measure: Adverse events occurring over the immediate 30-minute post vaccination
time frame: 30-minute post vaccination
description: Immediate Reactogenicity
measure: Number of participants with solicited local AE (erythema, swelling, induration, pain, tenderness, ecchymosis, pruritus) until 3 days post vaccination.
time frame: 3 days post vaccination
description: Solicited Local Adverse Events
measure: Number of participants with solicited systemic AEs (fever, fatigue, malaise, myalgia, arthralgia, chills, nausea, vomiting, and headache) until 3 days post vaccination.
time frame: 3 days post vaccination
description: Solicited Systemic Adverse Events
measure: Number of participants with unsolicited adverse events up to 3 days after vaccination.
time frame: 3 days after vaccination.
description: Unsolicited Adverse Events
measure: All adverse reactions with severity graded 3/4 over the entire study period.
time frame: 180 days after vaccination.
description: Adverse Reactions with severity graded 3/4
arm group label: Butantan Trivalent Influenza Vaccine
arm group type: Other
description: Butantan Institute Trivalent Seasonal Influenza Vaccine (IB-TIV): 15 μg influenza A/H1N1 antigen + 15 μg influenza A/H3N2 antigen + 15 μg influenza B antigen
Patients will receive one dose (0,5 ml) via intramuscular injection.
arm group label: Sanofi Trivalent Influenza Vaccine
arm group type: Other
description: Sanofi Trivalent Seasonal Influenza Vaccine (IB-TIV): 15 μg influenza A/H1N1 antigen + 15 μg influenza A/H3N2 antigen + 15 μg influenza B antigen
Patients will receive one dose (0,5 ml) via intramuscular injection.
intervention type: Biological
intervention name: Butantan Institute Trivalent Seasonal Influenza Vaccine
description: Butantan Institute and Pasteur-Mérieux (present, Sanofi Pasteur) established a technology transfer in 1999 for the production of a trivalent influenza vaccine of inactivated split-virion using embryonated eggs. The technology transfer followed a progressive approach from importing the finished product, to packaging and quality control test for release (1999), and, finally, to the first batch of influenza vaccine entirely produced by Butantan (2011). In 2013, the Butantan vaccine was registered by the Brazilian National Agency of Sanitary Surveillance (ANVISA).
arm group label: Butantan Trivalent Influenza Vaccine
intervention type: Biological
intervention name: Sanofi Trivalent Seasonal Influenza Vaccine
description: VAXIGRIP® was launched in 1968 and since then has been licensed in more than 100 countries and prequalified by WHO in 2011. Several clinical studies by Sanofi Pasteur have examined the safety and immunogenicity of Vaxigrip® in older children (8-10 years), adults (18-59 years), elderly (> 60 years),11,12 children (six months to three years) 13 and pregnant women.
arm group label: Sanofi Trivalent Influenza Vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 69 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Alexander Precioso, MD, PhD
role: Study Director
affiliation: Instituto butantan
facility: 
facility: 
facility: 
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: Influenza, Human
mesh term: Vaccines
sharing ipd: Undecided