<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/NCT02971670</url>
  </required_header>
  <id_info>
    <org_study_id>BioMed0713 B</org_study_id>
    <nct_id>NCT02971670</nct_id>
  </id_info>
  <brief_title>Amendment of rTSST-1 Variant Vaccine Phase 1 Clinical Trial</brief_title>
  <official_title>Amendment of Phase 1 Clinical Trial of the BioMed rTSST-1 Variant Vaccine in Healthy Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biomedizinische Forschungs gmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Biomedizinische Forschungs gmbH</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Toxic Shock Syndrome (TSS) a severe condition with high morbidity and mortality results from&#xD;
      the hosts overwhelming inflammatory response and cytokine storm. Staphylococcal superantigen&#xD;
      toxins are the main causative agents. Toxic shock syndrome toxin (TSST-1) being responsible&#xD;
      for almost all of menstruation associated and more than 50% of all other cases. There is no&#xD;
      specific therapy. The Phase I study BioMed0713 demonstrated the safety and tolerability of&#xD;
      the BioMed recombinant toxic shock syndrome toxin (rTSST-1) Variant Vaccine in healthy&#xD;
      adults.&#xD;
&#xD;
      The aim of this amendment is to demonstrate prolonged safety of the BioMed rTSST-1 Variant&#xD;
      Vaccine and to assess persistence of antibodies generated in participants. The second aim of&#xD;
      the study is to assess boosterability of the BioMed rTSST-1 Variant Vaccine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The BioMed rTSST-1 Variant Vaccine has been developed by Biomedizinische ForschungsgmbH as&#xD;
      one component of a polyvalent staphylococcal vaccine for the prevention of toxic shock and&#xD;
      hyperimmunization of donors for the production of TSST-1 immunoglobulin.&#xD;
&#xD;
      This is a prospective, single-blinded follow-up study of the safety and immunogenicity of the&#xD;
      BioMed rTSST1 Variant Vaccine compared to adjuvant in healthy adults.&#xD;
&#xD;
      All subjects who received 2 doses of 100 ng or more of the rTSST-1 Variant Candidate Vaccine&#xD;
      or placebo (Groups 1 - 6) will be followed up in a single-blinded manner for long-term&#xD;
      immunogenicity 6 - 15 months after their last (= second) immunization to gain more data about&#xD;
      persistence of TSST-1 Ab titer. As this part of the study occurs after unblinding of the&#xD;
      study subjects, it is termed Part B (for better discrimination from double-blinded Part A).&#xD;
&#xD;
      All participants will be invited for a blood withdrawal to determine TSST-1 antibodies.&#xD;
      Independent of the TSST-1 Ab titer level, subjects will receive one booster immunization&#xD;
      either according to their former allocated dose (group 4: 3µg or placebo, group 5: 10 µg or&#xD;
      placebo, group 6: 30 µg or placebo) or 3µg or placebo (groups 1 - 3) in the same visit.&#xD;
&#xD;
      Placebo will be administered according to the former allocated dose.&#xD;
&#xD;
      The treated subjects will stay two hours after immunization at the department and will be&#xD;
      followed up for 6 months.&#xD;
&#xD;
      Rationale for reduced monitoring after immunization and follow up:&#xD;
&#xD;
      The BioMed rTSST-1 Variant Vaccine demonstrated excellent local and systemic tolerability and&#xD;
      safety and an absence of adverse events classified as clinically relevant during the conduct&#xD;
      of the study. Therefore no abnormal findings are expected and the monitoring of the&#xD;
      vaccinated subjects after immunization is reduced to two hours, there are three follow up&#xD;
      visits planned, 24h (+-2 h), 28 days (+-7 days) and 6 months (+-28 days) after booster&#xD;
      vaccination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2015</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events as a Measure of Safety</measure>
    <time_frame>through 6 months</time_frame>
    <description>Clinical observation and clinical laboratory values</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Persistence of TSST-1 Antibodies</measure>
    <time_frame>6-15 months after last immunization of Phase I</time_frame>
    <description>ELISA IgG against rTSST-1. Persistence of antibody was defined as a &gt;/= 4-fold increase in TSST-1 Ab titer as compared to pre-vaccination values.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Boosterability of BioMed rTSST-1 Variant Vaccine</measure>
    <time_frame>through 6 months after third immunization</time_frame>
    <description>ELISA IgG against rTSST-1. Boosterability was defined as an increase in TSST-1 Ab titer as compared to antibody titers after second vaccination.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Toxic-Shock Syndrome</condition>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>Dose Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment: rTSST-1 Variant Candidate Vaccine 3 µg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment: rTSST-1 Variant Candidate Vaccine 10 µg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment: rTSST-1 Variant Candidate Vaccine 30 µg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Group 0</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Control: Al(OH)3 Adjuvant</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>rTSST-1 Variant Candidate Vaccine</intervention_name>
    <description>Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
    <arm_group_label>Dose Group 0</arm_group_label>
    <arm_group_label>Dose Group 1</arm_group_label>
    <arm_group_label>Dose Group 2</arm_group_label>
    <arm_group_label>Dose Group 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  male and female&#xD;
&#xD;
          -  18 - 64 years&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
          -  physical exam: no abnormal findings unless considered irrelevant by the investigator&#xD;
&#xD;
          -  uneventful medical history&#xD;
&#xD;
          -  females: adequate contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  positive virology markers at first screening&#xD;
&#xD;
          -  signs and symptoms of relevant autoimmunity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Martha M Eibl, MD</last_name>
    <role>Study Director</role>
    <affiliation>Biomedizinische ForschungsgmbH</affiliation>
  </overall_official>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <results_first_submitted>March 28, 2017</results_first_submitted>
  <results_first_submitted_qc>March 28, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 8, 2017</results_first_posted>
  <last_update_submitted>May 12, 2017</last_update_submitted>
  <last_update_submitted_qc>May 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2017</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>Shock, Septic</mesh_term>
    <mesh_term>Shock</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Dose Group 1</title>
          <description>Treatment: rTSST-1 Variant Candidate Vaccine 3 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
        </group>
        <group group_id="P2">
          <title>Dose Group 2</title>
          <description>Treatment: rTSST-1 Variant Candidate Vaccine 10 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
        </group>
        <group group_id="P3">
          <title>Dose Group 3</title>
          <description>Treatment: rTSST-1 Variant Candidate Vaccine 30 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
        </group>
        <group group_id="P4">
          <title>Dose Group 0</title>
          <description>Control: Al(OH)3 Adjuvant&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Dose Group 1</title>
          <description>Treatment: rTSST-1 Variant Candidate Vaccine 3 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
        </group>
        <group group_id="B2">
          <title>Dose Group 2</title>
          <description>Treatment: rTSST-1 Variant Candidate Vaccine 10 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
        </group>
        <group group_id="B3">
          <title>Dose Group 3</title>
          <description>Treatment: rTSST-1 Variant Candidate Vaccine 30 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
        </group>
        <group group_id="B4">
          <title>Dose Group 0</title>
          <description>Control: Al(OH)3 Adjuvant&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
        </group>
        <group group_id="B5">
          <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="13"/>
            <count group_id="B2" value="2"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="3"/>
            <count group_id="B5" value="23"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="23"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" 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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38.5" spread="10.1"/>
                    <measurement group_id="B2" value="45" spread="18.4"/>
                    <measurement group_id="B3" value="28.6" spread="7.9"/>
                    <measurement group_id="B4" value="31.3" spread="10.7"/>
                    <measurement group_id="B5" value="35.9" spread="10.9"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Austria</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Adverse Events as a Measure of Safety</title>
        <description>Clinical observation and clinical laboratory values</description>
        <time_frame>through 6 months</time_frame>
        <population>Out of 23 Subjects responding, 8 subjects were not interested to continue; 15 subjects were included as PP population.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Group 1</title>
            <description>Treatment: rTSST-1 Variant Candidate Vaccine 3 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
          </group>
          <group group_id="O2">
            <title>Dose Group 2</title>
            <description>Treatment: rTSST-1 Variant Candidate Vaccine 10 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
          </group>
          <group group_id="O3">
            <title>Dose Group 3</title>
            <description>Treatment: rTSST-1 Variant Candidate Vaccine 30 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
          </group>
          <group group_id="O4">
            <title>Dose Group 0</title>
            <description>Control: Al(OH)3 Adjuvant&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events as a Measure of Safety</title>
          <description>Clinical observation and clinical laboratory values</description>
          <population>Out of 23 Subjects responding, 8 subjects were not interested to continue; 15 subjects were included as PP population.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Persistence of TSST-1 Antibodies</title>
        <description>ELISA IgG against rTSST-1. Persistence of antibody was defined as a &gt;/= 4-fold increase in TSST-1 Ab titer as compared to pre-vaccination values.</description>
        <time_frame>6-15 months after last immunization of Phase I</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose Group 1</title>
            <description>Treatment: rTSST-1 Variant Candidate Vaccine 3 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
          </group>
          <group group_id="O2">
            <title>Dose Group 2</title>
            <description>Treatment: rTSST-1 Variant Candidate Vaccine 10 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
          </group>
          <group group_id="O3">
            <title>Dose Group 3</title>
            <description>Treatment: rTSST-1 Variant Candidate Vaccine 30 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
          </group>
          <group group_id="O4">
            <title>Dose Group 0</title>
            <description>Control: Al(OH)3 Adjuvant&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
          </group>
        </group_list>
        <measure>
          <title>Persistence of TSST-1 Antibodies</title>
          <description>ELISA IgG against rTSST-1. Persistence of antibody was defined as a &gt;/= 4-fold increase in TSST-1 Ab titer as compared to pre-vaccination values.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Boosterability of BioMed rTSST-1 Variant Vaccine</title>
        <description>ELISA IgG against rTSST-1. Boosterability was defined as an increase in TSST-1 Ab titer as compared to antibody titers after second vaccination.</description>
        <time_frame>through 6 months after third immunization</time_frame>
        <population>Out of 23 Subjects responding, 8 subjects were not interested to continue; 15 subjects were included as PP population.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Group 1</title>
            <description>Treatment: rTSST-1 Variant Candidate Vaccine 3 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
          </group>
          <group group_id="O2">
            <title>Dose Group 2</title>
            <description>Treatment: rTSST-1 Variant Candidate Vaccine 10 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
          </group>
          <group group_id="O3">
            <title>Dose Group 3</title>
            <description>Treatment: rTSST-1 Variant Candidate Vaccine 30 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
          </group>
          <group group_id="O4">
            <title>Dose Group 0</title>
            <description>Control: Al(OH)3 Adjuvant&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
          </group>
        </group_list>
        <measure>
          <title>Boosterability of BioMed rTSST-1 Variant Vaccine</title>
          <description>ELISA IgG against rTSST-1. Boosterability was defined as an increase in TSST-1 Ab titer as compared to antibody titers after second vaccination.</description>
          <population>Out of 23 Subjects responding, 8 subjects were not interested to continue; 15 subjects were included as PP population.</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="9"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Dose Group 1</title>
          <description>Treatment: rTSST-1 Variant Candidate Vaccine 3 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
        </group>
        <group group_id="E2">
          <title>Dose Group 2</title>
          <description>Treatment: rTSST-1 Variant Candidate Vaccine 10 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
        </group>
        <group group_id="E3">
          <title>Dose Group 3</title>
          <description>Treatment: rTSST-1 Variant Candidate Vaccine 30 µg&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
        </group>
        <group group_id="E4">
          <title>Dose Group 0</title>
          <description>Control: Al(OH)3 Adjuvant&#xD;
rTSST-1 Variant Candidate Vaccine: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Non-drug-related Hospitalization</sub_title>
                <description>Hospitalization became necessary subsequently to a radius fracture to surgically remove osteosynthesis material from the left arm.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="7" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Mild to moderate reactions</sub_title>
                <description>All other adverse events were mild to moderate, with symptoms as in Phase I (NCT02340338), and all were classified as not clinically relevant.</description>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
              </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 NOT 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>Dr. Martha M. Eibl</name_or_title>
      <organization>Biomedizinische Forschungsgesellschaft mbH</organization>
      <phone>+43-1-4081091</phone>
      <email>martha.eibl@meduniwien.ac.at</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/NCT02971670
org study id: BioMed0713 B
nct id: NCT02971670
lead sponsor: 
collaborator: 
has dmc: Yes
Toxic Shock Syndrome (TSS) a severe condition with high morbidity and mortality results from
      the hosts overwhelming inflammatory response and cytokine storm. Staphylococcal superantigen
      toxins are the main causative agents. Toxic shock syndrome toxin (TSST-1) being responsible
      for almost all of menstruation associated and more than 50% of all other cases. There is no
      specific therapy. The Phase I study BioMed0713 demonstrated the safety and tolerability of
      the BioMed recombinant toxic shock syndrome toxin (rTSST-1) Variant Vaccine in healthy
      adults.

      The aim of this amendment is to demonstrate prolonged safety of the BioMed rTSST-1 Variant
      Vaccine and to assess persistence of antibodies generated in participants. The second aim of
      the study is to assess boosterability of the BioMed rTSST-1 Variant Vaccine.
The BioMed rTSST-1 Variant Vaccine has been developed by Biomedizinische ForschungsgmbH as
      one component of a polyvalent staphylococcal vaccine for the prevention of toxic shock and
      hyperimmunization of donors for the production of TSST-1 immunoglobulin.

      This is a prospective, single-blinded follow-up study of the safety and immunogenicity of the
      BioMed rTSST1 Variant Vaccine compared to adjuvant in healthy adults.

      All subjects who received 2 doses of 100 ng or more of the rTSST-1 Variant Candidate Vaccine
      or placebo (Groups 1 - 6) will be followed up in a single-blinded manner for long-term
      immunogenicity 6 - 15 months after their last (= second) immunization to gain more data about
      persistence of TSST-1 Ab titer. As this part of the study occurs after unblinding of the
      study subjects, it is termed Part B (for better discrimination from double-blinded Part A).

      All participants will be invited for a blood withdrawal to determine TSST-1 antibodies.
      Independent of the TSST-1 Ab titer level, subjects will receive one booster immunization
      either according to their former allocated dose (group 4: 3µg or placebo, group 5: 10 µg or
      placebo, group 6: 30 µg or placebo) or 3µg or placebo (groups 1 - 3) in the same visit.

      Placebo will be administered according to the former allocated dose.

      The treated subjects will stay two hours after immunization at the department and will be
      followed up for 6 months.

      Rationale for reduced monitoring after immunization and follow up:

      The BioMed rTSST-1 Variant Vaccine demonstrated excellent local and systemic tolerability and
      safety and an absence of adverse events classified as clinically relevant during the conduct
      of the study. Therefore no abnormal findings are expected and the monitoring of the
      vaccinated subjects after immunization is reduced to two hours, there are three follow up
      visits planned, 24h (+-2 h), 28 days (+-7 days) and 6 months (+-28 days) after booster
      vaccination.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Number of Participants With Adverse Events as a Measure of Safety
time frame: through 6 months
description: Clinical observation and clinical laboratory values
measure: Persistence of TSST-1 Antibodies
time frame: 6-15 months after last immunization of Phase I
description: ELISA IgG against rTSST-1. Persistence of antibody was defined as a >/= 4-fold increase in TSST-1 Ab titer as compared to pre-vaccination values.
measure: Boosterability of BioMed rTSST-1 Variant Vaccine
time frame: through 6 months after third immunization
description: ELISA IgG against rTSST-1. Boosterability was defined as an increase in TSST-1 Ab titer as compared to antibody titers after second vaccination.
arm group label: Dose Group 1
arm group type: Experimental
description: Treatment: rTSST-1 Variant Candidate Vaccine 3 µg
arm group label: Dose Group 2
arm group type: Experimental
description: Treatment: rTSST-1 Variant Candidate Vaccine 10 µg
arm group label: Dose Group 3
arm group type: Experimental
description: Treatment: rTSST-1 Variant Candidate Vaccine 30 µg
arm group label: Dose Group 0
arm group type: Placebo Comparator
description: Control: Al(OH)3 Adjuvant
intervention type: Biological
intervention name: rTSST-1 Variant Candidate Vaccine
description: Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.
arm group label: Dose Group 0
arm group label: Dose Group 1
arm group label: Dose Group 2
arm group label: Dose Group 3
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Martha M Eibl, MD
role: Study Director
affiliation: Biomedizinische ForschungsgmbH
responsible party type: Sponsor
mesh term: Shock, Septic
mesh term: Shock
sharing ipd: Yes
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 