<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/NCT01701999</url>
  </required_header>
  <id_info>
    <org_study_id>rBV A/B-CL-001</org_study_id>
    <nct_id>NCT01701999</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, and Immunogenicity Study of Investigational Recombinant Botulinum Vaccine A/B (rBV A/B) in Volunteers Previously Immunized With Investigational Pentavalent Botulinum Toxoid</brief_title>
  <official_title>Phase 2b, Two-part, Open-label, Uncontrolled Study to Evaluate Safety, Tolerability, and Immunogenicity of a Single 40-µg Dose of Recombinant Botulinum Vaccine A/B (rBV A/B) for the Production of BabyBIG® in Volunteers Previously Immunized With Pentavalent Botulinum Toxoid for Occupational Protection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>California Department of Public Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>California Department of Public Health</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study rBV A/B-CL-001 is a Phase 2b, 2-part, open-label, uncontrolled study to evaluate&#xD;
      safety, tolerability, and immunogenicity of a single dose of recombinant botulinum vaccine&#xD;
      A/B (rBV A/B) for the production of BabyBIG in volunteers previously immunized with the&#xD;
      pentavalent botulinum (PBT) toxoid. This study is designed to determine neutralizing antibody&#xD;
      levels for botulinum toxin types A and B in healthy subjects who were previously immunized&#xD;
      with the PBT for occupational protection and who receive the rBV A/B. Subjects with titers of&#xD;
      the neutralizing antibodies against the toxins would be candidates for plasma donation for&#xD;
      BabyBIG production.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Four-Fold Increase in Neutralizing Antibody Concentration (NAC)</measure>
    <time_frame>Week 0 to Week 4</time_frame>
    <description>Proportion of participants achieving a four-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Three-Fold Increase in Neutralizing Antibody Concentration (NAC)</measure>
    <time_frame>Week 0 to Week 4</time_frame>
    <description>Proportion of participants achieving a three-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Two-Fold Increase in the Area Under the Neutralizing Antibody Concentration (NAC) Curve</measure>
    <time_frame>Week 0 to Week 12</time_frame>
    <description>Proportion of participants achieving a two-fold increase in the area under the plasma NAC-time curve between Week 0 and Week 12 in comparison with a straight-line extension of the Week 0 NAC to Week 12 for both botulinum toxin A and toxin B. A proportion ≥ 0.50 was considered a success.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Collected Plasma Volume</measure>
    <time_frame>Week 1 to Week 12</time_frame>
    <description>Measurement of the volume of source plasma containing neutralizing antibodies against botulinum toxin type A and type B collected by plasmapheresis in Part 2.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Botulism</condition>
  <arm_group>
    <arm_group_label>Vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>rBV A/B</intervention_name>
    <description>rBV A/B injections will consist of a single 40 µg injection of total antigen (20 µg of Antigen A and 20 µg of Antigen B) adsorbed to 0.2% (wt/vol) Alhydrogel™, in a total dose volume of 0.5 mL. The vaccine will be administered by intramuscular injection in the deltoid muscle, preferably in the nondominant arm.</description>
    <arm_group_label>Vaccine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The volunteer has received pentavalent botulinum toxoid for occupational protection&#xD;
             under BB IND 0161, with the previous pentavalent botulinum toxoid dose at least 6&#xD;
             months prior to the planned rBV A/B dose.&#xD;
&#xD;
          -  The volunteer is between the ages of 18 and 69 years at the time of consent.&#xD;
&#xD;
          -  The volunteer is healthy and has an acceptable medical history.&#xD;
&#xD;
          -  The volunteer meets the subject suitability requirements and recommendations for&#xD;
             source plasma donors (for Part 2 subjects only).&#xD;
&#xD;
          -  The volunteer, if female and of childbearing potential, is not pregnant or lactating,&#xD;
             and agrees to use an acceptable form of FDA-approved contraception for the duration of&#xD;
             the study.&#xD;
&#xD;
          -  The volunteer has the ability to understand the requirements of the study and provide&#xD;
             informed consent.&#xD;
&#xD;
          -  The volunteer agrees to complete the subject diary on a daily basis for 7 days&#xD;
             post-vaccination and to report concomitant medication and adverse events during the&#xD;
             study period.&#xD;
&#xD;
          -  The volunteer provides written authorization for use and disclosure of protected&#xD;
             health information.&#xD;
&#xD;
          -  The volunteer agrees not to donate blood or blood products (outside of study&#xD;
             procedures) during the course of the study.&#xD;
&#xD;
          -  The volunteer has personal health insurance.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Be pregnant or nursing&#xD;
&#xD;
          -  The volunteer has a history of laboratory evidence of syphilis, acquired&#xD;
             immunodeficiency syndrome, Creutzfeldt-Jakob disease, or infection with human&#xD;
             immunodeficiency viruses 1 or 2, human T cell lymphotropic virus 1, hepatitis B virus,&#xD;
             or hepatitis C virus.&#xD;
&#xD;
          -  The volunteer had prior severe local or severe systemic reaction to last immunization&#xD;
             with pentavalent botulinum toxoid.&#xD;
&#xD;
          -  The volunteer has a known allergy to aluminum compounds, yeast, or other components of&#xD;
             the vaccine.&#xD;
&#xD;
          -  The volunteer has donated one or more units of blood or undergone plasmapheresis&#xD;
             within 28 days before screening.&#xD;
&#xD;
          -  The volunteer has received a blood product or immunoglobulin within 6 months of&#xD;
             screening or plans to receive such products during the study.&#xD;
&#xD;
          -  The volunteer has received licensed nonliving vaccine within 14 days before study&#xD;
             entry or licensed live vaccine within 60 days before study entry.&#xD;
&#xD;
          -  The volunteer has received investigational products (drugs, biologics, vaccines, or&#xD;
             implantable devices) 60 days prior to study entry or plans to receive experimental&#xD;
             products at any time during the study.&#xD;
&#xD;
          -  The volunteer has received prescription immunosuppressive or immunomodulatory agents,&#xD;
             including parenteral, inhaled, or oral corticosteroids within 3 months before&#xD;
             screening or plans on receiving such therapy at any time during the study with the&#xD;
             exceptions (Subjects who have used prescription topical steroids may be enrolled 2&#xD;
             weeks after the therapy is completed; Intra-articular, bursal, or tendon injectable&#xD;
             steroids are permitted; Any over-the-counter topical steroid use is permitted;&#xD;
             Ophthalmic and intranasal steroids are permitted).&#xD;
&#xD;
          -  The volunteer has received cytotoxic therapy at any time in the previous 5 years to&#xD;
             study entry.&#xD;
&#xD;
          -  The volunteer has an active systemic or recurrent disease that would place the subject&#xD;
             at unacceptable risk of injury, require hospitalization, or require surgical&#xD;
             intervention.&#xD;
&#xD;
          -  The volunteer has a history of alcohol or drug abuse within 12 months before&#xD;
             screening.&#xD;
&#xD;
          -  The volunteer has past, present, or suspected illicit injection drug use.&#xD;
&#xD;
          -  The volunteer has inflammatory, vasculitic, or rheumatic disease, including systemic&#xD;
             lupus erythematosus, polymyalgia rheumatica, rheumatoid arthritis, or scleroderma.&#xD;
&#xD;
          -  The volunteer has clinically recognized hepatic or renal insufficiency.&#xD;
&#xD;
          -  The volunteer has uncontrolled hypertension.&#xD;
&#xD;
          -  The volunteer has moderate to severe asthma, chronic obstructive pulmonary disease, or&#xD;
             other significant pulmonary disease.&#xD;
&#xD;
          -  The volunteer has a seizure disorder.&#xD;
&#xD;
          -  The volunteer has moderate or severe illness or oral temperature of 100.4°F or greater&#xD;
             within 3 days prior to immunization.&#xD;
&#xD;
          -  The volunteer is determined by the investigator to be unsuitable for participation in&#xD;
             this trial for any reason.&#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>Stephen S. Arnon, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>California Department of Public Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>California Department of Public Health</name>
      <address>
        <city>Richmond</city>
        <state>California</state>
        <zip>94804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Battelle Biomedical Research Center</name>
      <address>
        <city>West Jefferson</city>
        <state>Ohio</state>
        <zip>43162</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.infantbotulism.org/</url>
    <description>Related Info</description>
  </link>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>October 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 5, 2012</study_first_posted>
  <results_first_submitted>December 15, 2016</results_first_submitted>
  <results_first_submitted_qc>December 15, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 9, 2017</results_first_posted>
  <disposition_first_submitted>September 26, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>September 26, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">September 28, 2016</disposition_first_posted>
  <last_update_submitted>April 19, 2017</last_update_submitted>
  <last_update_submitted_qc>April 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 16, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Botulism Vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulism</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Initial Safety and Immunogenicity (Part 1)</title>
          <description>Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.</description>
        </group>
        <group group_id="P2">
          <title>Safety, Immunogenicity, and Plasma Collection (Part 2)</title>
          <description>Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Initial Safety and Immunogenicity (Part 1)</title>
          <description>Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.</description>
        </group>
        <group group_id="B2">
          <title>Safety, Immunogenicity, and Plasma Collection (Part 2)</title>
          <description>Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.</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="8"/>
            <count group_id="B2" value="37"/>
            <count group_id="B3" value="45"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="50.3" spread="13.5"/>
                    <measurement group_id="B2" value="44.0" spread="10.7"/>
                    <measurement group_id="B3" value="45.1" spread="11.3"/>
                  </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="3"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Four-Fold Increase in Neutralizing Antibody Concentration (NAC)</title>
        <description>Proportion of participants achieving a four-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success).</description>
        <time_frame>Week 0 to Week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Initial Safety and Immunogenicity (Part 1)</title>
            <description>Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Safety, Immunogenicity, and Plasma Collection (Part 2)</title>
            <description>Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Four-Fold Increase in Neutralizing Antibody Concentration (NAC)</title>
          <description>Proportion of participants achieving a four-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success).</description>
          <units>proportion of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Type A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.75"/>
                    <measurement group_id="O2" value="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Type B</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.75"/>
                    <measurement group_id="O2" value="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Three-Fold Increase in Neutralizing Antibody Concentration (NAC)</title>
        <description>Proportion of participants achieving a three-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success)</description>
        <time_frame>Week 0 to Week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Initial Safety and Immunogenicity (Part 1)</title>
            <description>Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Safety, Immunogenicity, and Plasma Collection (Part 2)</title>
            <description>Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Three-Fold Increase in Neutralizing Antibody Concentration (NAC)</title>
          <description>Proportion of participants achieving a three-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success)</description>
          <units>proportion of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Type A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.75"/>
                    <measurement group_id="O2" value="0.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Type B</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.75"/>
                    <measurement group_id="O2" value="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Two-Fold Increase in the Area Under the Neutralizing Antibody Concentration (NAC) Curve</title>
        <description>Proportion of participants achieving a two-fold increase in the area under the plasma NAC-time curve between Week 0 and Week 12 in comparison with a straight-line extension of the Week 0 NAC to Week 12 for both botulinum toxin A and toxin B. A proportion ≥ 0.50 was considered a success.</description>
        <time_frame>Week 0 to Week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Initial Safety and Immunogenicity (Part 1)</title>
            <description>Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Safety, Immunogenicity, and Plasma Collection (Part 2)</title>
            <description>Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Two-Fold Increase in the Area Under the Neutralizing Antibody Concentration (NAC) Curve</title>
          <description>Proportion of participants achieving a two-fold increase in the area under the plasma NAC-time curve between Week 0 and Week 12 in comparison with a straight-line extension of the Week 0 NAC to Week 12 for both botulinum toxin A and toxin B. A proportion ≥ 0.50 was considered a success.</description>
          <units>proportion of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Type A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.75"/>
                    <measurement group_id="O2" value="0.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Type B</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.88"/>
                    <measurement group_id="O2" value="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Collected Plasma Volume</title>
        <description>Measurement of the volume of source plasma containing neutralizing antibodies against botulinum toxin type A and type B collected by plasmapheresis in Part 2.</description>
        <time_frame>Week 1 to Week 12</time_frame>
        <population>Participants in Part 1 were only analyzed for safety data, and one participant in Part 2 was excluded from plasma collection due to not meeting the plasma donor minimum weight requirement.</population>
        <group_list>
          <group group_id="O1">
            <title>Initial Safety and Immunogenicity (Part 1)</title>
            <description>Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.</description>
          </group>
          <group group_id="O2">
            <title>Safety, Immunogenicity, and Plasma Collection (Part 2)</title>
            <description>Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Collected Plasma Volume</title>
          <description>Measurement of the volume of source plasma containing neutralizing antibodies against botulinum toxin type A and type B collected by plasmapheresis in Part 2.</description>
          <population>Participants in Part 1 were only analyzed for safety data, and one participant in Part 2 was excluded from plasma collection due to not meeting the plasma donor minimum weight requirement.</population>
          <units>mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="13463.3" spread="4440.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Six months following rBV A/B administration</time_frame>
      <desc>Adverse events (AEs) indicated with * were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.</desc>
      <group_list>
        <group group_id="E1">
          <title>Initial Safety and Immunogenicity (Part 1)</title>
          <description>Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.</description>
        </group>
        <group group_id="E2">
          <title>Safety, Immunogenicity, and Plasma Collection (Part 2)</title>
          <description>Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA, Version 16.0</default_vocab>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Nausea*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Injection site anaesthesia*</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Injection site erythema*</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Injection site induration*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Injection site nodule*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Injection site pain*</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Injection site papule</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Injection site pruritus*</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Injection site reaction*</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Injection site swelling*</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Injection site urticaria*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Malaise*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pain*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pyrexia*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Swelling*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion site hematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Injection site swelling*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Procedural complication*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Blood potassium increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Blood urine present</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Body temperature increased*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Haematocrit decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Haemaglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Haemaglobin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Protein total decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Urine ketone body present</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Muscular weakness*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain*</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Myalgia*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Sensation of heaviness*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Headache*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Paraesthesia*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pulmonary congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Erythema*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Rash erythematous*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Rash papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Skin lesion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Sunburn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Urticaria*</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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. Jessica Khouri</name_or_title>
      <organization>California Department of Public Health</organization>
      <phone>510-231-7600</phone>
      <email>Jessica.Khouri@cdph.ca.gov</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/NCT01701999
org study id: rBV A/B-CL-001
nct id: NCT01701999
lead sponsor: 
has dmc: Yes
Study rBV A/B-CL-001 is a Phase 2b, 2-part, open-label, uncontrolled study to evaluate
      safety, tolerability, and immunogenicity of a single dose of recombinant botulinum vaccine
      A/B (rBV A/B) for the production of BabyBIG in volunteers previously immunized with the
      pentavalent botulinum (PBT) toxoid. This study is designed to determine neutralizing antibody
      levels for botulinum toxin types A and B in healthy subjects who were previously immunized
      with the PBT for occupational protection and who receive the rBV A/B. Subjects with titers of
      the neutralizing antibodies against the toxins would be candidates for plasma donation for
      BabyBIG production.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Four-Fold Increase in Neutralizing Antibody Concentration (NAC)
time frame: Week 0 to Week 4
description: Proportion of participants achieving a four-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success).
measure: Three-Fold Increase in Neutralizing Antibody Concentration (NAC)
time frame: Week 0 to Week 4
description: Proportion of participants achieving a three-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success)
measure: Two-Fold Increase in the Area Under the Neutralizing Antibody Concentration (NAC) Curve
time frame: Week 0 to Week 12
description: Proportion of participants achieving a two-fold increase in the area under the plasma NAC-time curve between Week 0 and Week 12 in comparison with a straight-line extension of the Week 0 NAC to Week 12 for both botulinum toxin A and toxin B. A proportion ≥ 0.50 was considered a success.
measure: Collected Plasma Volume
time frame: Week 1 to Week 12
description: Measurement of the volume of source plasma containing neutralizing antibodies against botulinum toxin type A and type B collected by plasmapheresis in Part 2.
arm group label: Vaccine
arm group type: Experimental
intervention type: Biological
intervention name: rBV A/B
description: rBV A/B injections will consist of a single 40 µg injection of total antigen (20 µg of Antigen A and 20 µg of Antigen B) adsorbed to 0.2% (wt/vol) Alhydrogel™, in a total dose volume of 0.5 mL. The vaccine will be administered by intramuscular injection in the deltoid muscle, preferably in the nondominant arm.
arm group label: Vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 69 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Stephen S. Arnon, M.D.
role: Principal Investigator
affiliation: California Department of Public Health
facility: 
facility: 
country: United States
url: http://www.infantbotulism.org/
description: Related Info
responsible party type: Sponsor
mesh term: Botulism
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 