<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/NCT03264157</url>
  </required_header>
  <id_info>
    <org_study_id>RIG01</org_study_id>
    <nct_id>NCT03264157</nct_id>
  </id_info>
  <brief_title>Safety and Effectiveness of BPL HRIG With Active Rabies Vaccine in Healthy Subjects</brief_title>
  <official_title>A Prospective, Randomized, Double-Blind Parallel-group, Non-inferiority Phase II/III Study of the Safety and Effectiveness of BPL HRIG With Co Administration of Active Rabies Vaccine in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bio Products Laboratory</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bio Products Laboratory</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective, randomized, blinded, parallel-group, non-inferiority, phase II/III study of&#xD;
      the safety and effectiveness of simulated post-exposure prophylaxis with BPL HRIG with&#xD;
      co-administration of active rabies vaccine in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Each subject will undergo a total of 9 visits. Subjects' eligibility will be assessed at&#xD;
      Screening, which can occur up to 28 days prior to dosing. Following a repeat eligibility&#xD;
      check at Day 0, eligible subjects will be randomized and dosed with the randomized treatment&#xD;
      (BPL HRIG + vaccine or Comparator HRIG + vaccine) on Day 0. Further assessments will be&#xD;
      conducted on Days 3, 5, 7, 14, 28, 49 and the end of study assessment on Day 140. Vaccine&#xD;
      will be administered on Day 0, 3, 7, 14 and 28.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 8, 2017</start_date>
  <completion_date type="Actual">July 13, 2018</completion_date>
  <primary_completion_date type="Actual">March 2, 2018</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Treatment A: BPL HRIG + active rabies vaccine Treatment B: Comparator HRIG + active rabies vaccine</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double-blind study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Subjects With Anti-rabies Antibody Titer of ≥0.5 IU/mL</measure>
    <time_frame>Day 14</time_frame>
    <description>Non-inferiority in terms of the proportion of subjects with anti-rabies antibody titer of ≥0.5 IU/mL after study drug administration using a non-inferiority margin of 10%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Analysis of AUC0-7d</measure>
    <time_frame>Day 0 to Day 7</time_frame>
    <description>The AUC0-7d for BPL HRIG and vaccine versus comparator HRIG and vaccine using a non inferiority margin of 20%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RVNA Geometric Mean Titers at Days 3, 5, 7 and 14</measure>
    <time_frame>Days 3, 5, 7 and 14</time_frame>
    <description>Comparison of the geometric mean titers (GMTs) for antirabies antibody titer after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine. The median peak RVNA titer occurred at Day 14, which is reflected in the analysis. The RVNA titer to peak geometric mean is analyzed using a repeated measures analysis. The inferential test compares RVNA values between BPL HRIG and HyperRab in a single analysis across all visits at or below the visit at which peak titer is observed. The geometric mean values presented represent a mean across all visits from baseline through and including Day 14.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit</measure>
    <time_frame>Days 3, 5, 7, 14, 28, 49, and 140</time_frame>
    <description>The proportion of subjects reaching antirabies antibody titer of ≥ 0.5 IU/mL after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit</measure>
    <time_frame>Days 3, 5, 7, 14, 28, 49, and 140</time_frame>
    <description>The proportion of subjects reaching antirabies antibody titer of ≥ LLOQ of the assay at each visit after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RVNA Geometric Mean Titers at Days 14, 28, 49 and 140</measure>
    <time_frame>Days 14, 28, 49 and 140</time_frame>
    <description>Comparison of the GMTs for antirabies antibody titer after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine to assess the inhibitory effects of BPL HRIG on active immunization relative to that of the comparator HRIG.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">162</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BPL HRIG + RabAvert</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 IU/kg dose HRIG + active rabies vaccine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparator HyperRab + RabAvert</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 IU/kg dose HRIG + active rabies vaccine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HRIG</intervention_name>
    <description>A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.</description>
    <arm_group_label>BPL HRIG + RabAvert</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HyperRAB</intervention_name>
    <description>A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.</description>
    <arm_group_label>Comparator HyperRab + RabAvert</arm_group_label>
    <other_name>HRIG</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RabAvert</intervention_name>
    <description>A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.</description>
    <arm_group_label>BPL HRIG + RabAvert</arm_group_label>
    <arm_group_label>Comparator HyperRab + RabAvert</arm_group_label>
    <other_name>active rabies vaccine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Able and willing to sign an informed consent form.&#xD;
&#xD;
          2. Healthy male or female subjects aged 18 - 75 years inclusive.&#xD;
&#xD;
          3. No previous exposure to rabies virus, rabies vaccine and/or rabies immunoglobulin.&#xD;
&#xD;
          4. No significant abnormalities in hematology, biochemistry, or urinalysis according to&#xD;
             the Principal Investigator's judgment.&#xD;
&#xD;
          5. No significant abnormalities in ECG according to the Investigator's judgment.&#xD;
&#xD;
          6. Females of child-bearing potential (defined from the onset of menstruation to one-year&#xD;
             post- menopause and not surgically sterilized) who are (or become) sexually active&#xD;
             must agree to practice contraception by using a highly effective (&gt;98%) method for the&#xD;
             duration of the study.&#xD;
&#xD;
          7. Females of child-bearing potential (defined from the onset of menstruation to one-year&#xD;
             post- menopause and not surgically sterilized) must have a negative result on a serum&#xD;
             at screening visit and a urine HCG-based pregnancy test at Day 0.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Female subjects who are pregnant and/or lactating.&#xD;
&#xD;
          2. History of live virus vaccination, e.g., measles, mumps, varicella or rubella vaccine,&#xD;
             within the last 3 months.&#xD;
&#xD;
          3. Planned live virus vaccination, e.g., measles, mumps, varicella or rubella vaccine,&#xD;
             within the 3 months after Day 0.&#xD;
&#xD;
          4. History of anaphylactic or anaphylactoid hypersensitivity reactions to chicken egg;&#xD;
             history of mild allergic reactions to chicken egg, e.g., skin rash only, is not an&#xD;
             exclusion criterion&#xD;
&#xD;
          5. History of hypersensitivity reaction to any of the following components of active&#xD;
             rabies vaccine (US-FDA approved) e.g.: neomycin, bovine gelatin, trace amounts of&#xD;
             chicken protein, chlortetracycline, and amphotericin B and in accordance with the&#xD;
             product insert of the vaccine.&#xD;
&#xD;
          6. History of life-threatening allergy, anaphylactic reaction, or systemic response to&#xD;
             human plasma derived products.&#xD;
&#xD;
          7. History of life-threatening allergy to blood or blood products.&#xD;
&#xD;
          8. Fever at the time of the start of the injection (oral temperature &gt;38ºC.) or acute&#xD;
             illness at the time of the start of the injection. Subjects with fever on Day 0 may&#xD;
             have entry to the study re-scheduled.&#xD;
&#xD;
          9. History of or ongoing bleeding disorder.&#xD;
&#xD;
         10. Previous organ transplant recipient.&#xD;
&#xD;
         11. Ongoing immunosuppressive illness.&#xD;
&#xD;
         12. Clinically significant illnesses including: cardiac, hepatic, renal, endocrine,&#xD;
             neurological, hematological, neoplastic, immunological, skeletal or other) that in the&#xD;
             opinion of the investigator, could interfere with the safety, compliance or other&#xD;
             aspects of this study.&#xD;
&#xD;
         13. All types of malignancies except for basal and squamous cell (scaly or plate-like)&#xD;
             skin cancer, in- situ cervical carcinoma must be in remission for a minimum of 5 years&#xD;
             prior to Day 0. For non-melanoma skin cancers and carcinoma in-situ of the cervix may&#xD;
             be enrolled if treated and cured at the time of screening.&#xD;
&#xD;
         14. Evidence of active systemic infection that requires treatment with antibiotics within&#xD;
             2 weeks prior to Day 0.&#xD;
&#xD;
         15. Currently receiving or have received within the past 6 months (prior to Day 0):&#xD;
&#xD;
               -  immunosuppressive drugs&#xD;
&#xD;
               -  immunomodulatory drugs&#xD;
&#xD;
         16. Currently receiving or have received oral or IV steroids within 14 days (prior to DAY&#xD;
             0) or expected to require oral or IV steroids during the study.&#xD;
&#xD;
         17. Evidence of uncontrolled hypertension (systolic blood pressure of &gt;150 mmHg, and/or&#xD;
             diastolic blood pressure of &gt;100 mmHg).&#xD;
&#xD;
         18. Heart rate &gt;120/min.&#xD;
&#xD;
         19. Weight &gt; 95.5 kg&#xD;
&#xD;
         20. History of IgA deficiency.&#xD;
&#xD;
         21. Is positive for any of the following at screening: serological test for HIV 1&amp;2, HCV&#xD;
             or HBsAg.&#xD;
&#xD;
         22. Presence of psychiatric disorder, other mental disorder or any other medical disorder&#xD;
             which might impair the subject's ability to give informed consent or to comply with&#xD;
             the requirements of the study protocol.&#xD;
&#xD;
         23. Previous enrollment in this study.&#xD;
&#xD;
         24. Participation in an interventional clinical trial within 30 days prior to baseline&#xD;
             visit (Day 0).&#xD;
&#xD;
         25. Evidence of alcohol abuse or history of alcohol abuse or illegal and/or legally&#xD;
             prescribed drugs in the past 2 years.&#xD;
&#xD;
         26. Any other factor that, in the opinion of the investigator, would prevent the subject&#xD;
             from complying with the requirements of the protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elizabeth Holmes, MD</last_name>
    <role>Study Director</role>
    <affiliation>Bio Products Laboratory</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Prism Research</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Research Associates</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <results_first_submitted>January 30, 2020</results_first_submitted>
  <results_first_submitted_qc>January 30, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">February 11, 2020</results_first_posted>
  <disposition_first_submitted>July 11, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>July 11, 2019</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">July 17, 2019</disposition_first_posted>
  <last_update_submitted>February 12, 2020</last_update_submitted>
  <last_update_submitted_qc>February 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rabies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 26, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT03264157/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 31, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT03264157/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>BPL HRIG + RabAvert</title>
          <description>20 IU/kg dose HRIG + active rabies vaccine&#xD;
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.&#xD;
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.</description>
        </group>
        <group group_id="P2">
          <title>Comparator HyperRab + RabAvert</title>
          <description>20 IU/kg dose HRIG + active rabies vaccine&#xD;
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.&#xD;
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="81"/>
                <participants group_id="P2" count="81"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="68"/>
                <participants group_id="P2" count="74"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>BPL HRIG + RabAvert</title>
          <description>20 IU/kg dose HRIG + active rabies vaccine&#xD;
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.&#xD;
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.</description>
        </group>
        <group group_id="B2">
          <title>Comparator HyperRab + RabAvert</title>
          <description>20 IU/kg dose HRIG + active rabies vaccine&#xD;
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.&#xD;
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.</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="81"/>
            <count group_id="B2" value="81"/>
            <count group_id="B3" value="162"/>
          </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="41.37" spread="15.0"/>
                    <measurement group_id="B2" value="44.56" spread="15.4"/>
                    <measurement group_id="B3" value="42.96" spread="15.2"/>
                  </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="56"/>
                    <measurement group_id="B2" value="54"/>
                    <measurement group_id="B3" value="110"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="79"/>
                    <measurement group_id="B2" value="78"/>
                    <measurement group_id="B3" value="157"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="62"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="121"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="81"/>
                    <measurement group_id="B2" value="81"/>
                    <measurement group_id="B3" value="162"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74.61" spread="12.5"/>
                    <measurement group_id="B2" value="74.51" spread="13.2"/>
                    <measurement group_id="B3" value="74.56" spread="12.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Subjects With Anti-rabies Antibody Titer of ≥0.5 IU/mL</title>
        <description>Non-inferiority in terms of the proportion of subjects with anti-rabies antibody titer of ≥0.5 IU/mL after study drug administration using a non-inferiority margin of 10%.</description>
        <time_frame>Day 14</time_frame>
        <population>Primary PK population (all subjects who receive the full dose of BPL HRIG or comparator HRIG and the first 3 doses of active rabies vaccine on Days 0, 3, 7 and for whom the PK sample at Day 14 is taken).</population>
        <group_list>
          <group group_id="O1">
            <title>BPL HRIG + RabAvert</title>
            <description>20 IU/kg dose HRIG + active rabies vaccine&#xD;
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.&#xD;
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.</description>
          </group>
          <group group_id="O2">
            <title>Comparator HyperRab + RabAvert</title>
            <description>20 IU/kg dose HRIG + active rabies vaccine&#xD;
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.&#xD;
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Subjects With Anti-rabies Antibody Titer of ≥0.5 IU/mL</title>
          <description>Non-inferiority in terms of the proportion of subjects with anti-rabies antibody titer of ≥0.5 IU/mL after study drug administration using a non-inferiority margin of 10%.</description>
          <population>Primary PK population (all subjects who receive the full dose of BPL HRIG or comparator HRIG and the first 3 doses of active rabies vaccine on Days 0, 3, 7 and for whom the PK sample at Day 14 is taken).</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="73"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>The null hypothesis is p-p0 ≤ -0.1. The alternative hypothesis is p-p0 &gt; -0.1, where p is the proportion of subjects with anti-rabies titer of &gt;0.5 IU/mL at Day 14 in subjects receiving BPL HRIG + vaccine and p0 is the proportion receiving comparator HRIG + vaccine. We reject the null hypothesis at the one-sided 0.025 significance level, and conclude that p-p0 &gt; -0.1, if the lower bound of an exact 95% binomial confidence interval exceeds -0.1.</non_inferiority_desc>
            <p_value>0.0006</p_value>
            <p_value_desc>The threshold for this test is &lt;=0.025.</p_value_desc>
            <method>Farrington and Manning test</method>
            <param_type>lower 95% CI</param_type>
            <param_value>-0.05</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
            <ci_lower_limit>-0.05</ci_lower_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Analysis of AUC0-7d</title>
        <description>The AUC0-7d for BPL HRIG and vaccine versus comparator HRIG and vaccine using a non inferiority margin of 20%.</description>
        <time_frame>Day 0 to Day 7</time_frame>
        <population>Primary PK population (all subjects who receive the full dose of BPL HRIG or comparator HRIG and the first 3 doses of active rabies vaccine on Days 0, 3, 7 and for whom the PK sample at Day 14 is taken).</population>
        <group_list>
          <group group_id="O1">
            <title>BPL HRIG + RabAvert</title>
            <description>20 IU/kg dose HRIG + active rabies vaccine&#xD;
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.&#xD;
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.</description>
          </group>
          <group group_id="O2">
            <title>Comparator HyperRab + RabAvert</title>
            <description>20 IU/kg dose HRIG + active rabies vaccine&#xD;
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.&#xD;
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.</description>
          </group>
        </group_list>
        <measure>
          <title>Analysis of AUC0-7d</title>
          <description>The AUC0-7d for BPL HRIG and vaccine versus comparator HRIG and vaccine using a non inferiority margin of 20%.</description>
          <population>Primary PK population (all subjects who receive the full dose of BPL HRIG or comparator HRIG and the first 3 doses of active rabies vaccine on Days 0, 3, 7 and for whom the PK sample at Day 14 is taken).</population>
          <units>day*IU/mL</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="73"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.10" lower_limit="1.02" upper_limit="1.20"/>
                    <measurement group_id="O2" value="1.32" lower_limit="1.21" upper_limit="1.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>The prespecified non inferiority margin was 20%. The lower bound of the 95% CI required should be greater than 0.8 to conclude non-inferiority.</non_inferiority_desc>
            <param_type>lower 95% CI</param_type>
            <param_value>0.74</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.74</ci_lower_limit>
            <ci_upper_limit>0.94</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>RVNA Geometric Mean Titers at Days 3, 5, 7 and 14</title>
        <description>Comparison of the geometric mean titers (GMTs) for antirabies antibody titer after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine. The median peak RVNA titer occurred at Day 14, which is reflected in the analysis. The RVNA titer to peak geometric mean is analyzed using a repeated measures analysis. The inferential test compares RVNA values between BPL HRIG and HyperRab in a single analysis across all visits at or below the visit at which peak titer is observed. The geometric mean values presented represent a mean across all visits from baseline through and including Day 14.</description>
        <time_frame>Days 3, 5, 7 and 14</time_frame>
        <population>Secondary PK population (subjects who receive the full dose of BPL HRIG or comparator HRIG and all 5 doses of active rabies vaccine and for whom all required PK samples are taken).</population>
        <group_list>
          <group group_id="O1">
            <title>BPL HRIG + RabAvert</title>
            <description>20 IU/kg dose HRIG + active rabies vaccine</description>
          </group>
          <group group_id="O2">
            <title>Comparator HyperRab + RabAvert</title>
            <description>20 IU/kg dose HRIG + active rabies vaccine</description>
          </group>
        </group_list>
        <measure>
          <title>RVNA Geometric Mean Titers at Days 3, 5, 7 and 14</title>
          <description>Comparison of the geometric mean titers (GMTs) for antirabies antibody titer after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine. The median peak RVNA titer occurred at Day 14, which is reflected in the analysis. The RVNA titer to peak geometric mean is analyzed using a repeated measures analysis. The inferential test compares RVNA values between BPL HRIG and HyperRab in a single analysis across all visits at or below the visit at which peak titer is observed. The geometric mean values presented represent a mean across all visits from baseline through and including Day 14.</description>
          <population>Secondary PK population (subjects who receive the full dose of BPL HRIG or comparator HRIG and all 5 doses of active rabies vaccine and for whom all required PK samples are taken).</population>
          <units>IU/mL</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Through Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.37" lower_limit="0.35" upper_limit="0.39"/>
                    <measurement group_id="O2" value="0.38" lower_limit="0.36" upper_limit="0.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.18" lower_limit="0.16" upper_limit="0.20"/>
                    <measurement group_id="O2" value="0.21" lower_limit="0.19" upper_limit="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.19" lower_limit="0.18" upper_limit="0.21"/>
                    <measurement group_id="O2" value="0.24" lower_limit="0.21" upper_limit="0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.23" lower_limit="0.21" upper_limit="0.26"/>
                    <measurement group_id="O2" value="0.26" lower_limit="0.23" upper_limit="0.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.30" lower_limit="10.15" upper_limit="14.90"/>
                    <measurement group_id="O2" value="8.38" lower_limit="6.54" upper_limit="10.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>95% CI</param_type>
            <param_value>0.97</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Data analyzed as log normal. The value presented is the untransformed value of the difference between means.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit</title>
        <description>The proportion of subjects reaching antirabies antibody titer of ≥ 0.5 IU/mL after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine.</description>
        <time_frame>Days 3, 5, 7, 14, 28, 49, and 140</time_frame>
        <population>Primary PK population (all subjects who receive the full dose of BPL HRIG or comparator HRIG and the first 3 doses of active rabies vaccine on Days 0, 3, 7 and for whom the PK sample at Day 14 is taken).</population>
        <group_list>
          <group group_id="O1">
            <title>BPL HRIG + RabAvert</title>
            <description>20 IU/kg dose HRIG + active rabies vaccine</description>
          </group>
          <group group_id="O2">
            <title>Comparator HyperRab + RabAvert</title>
            <description>20 IU/kg dose HRIG + active rabies vaccine</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit</title>
          <description>The proportion of subjects reaching antirabies antibody titer of ≥ 0.5 IU/mL after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine.</description>
          <population>Primary PK population (all subjects who receive the full dose of BPL HRIG or comparator HRIG and the first 3 doses of active rabies vaccine on Days 0, 3, 7 and for whom the PK sample at Day 14 is taken).</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="73"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="71"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 49</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="72"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 140</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="62"/>
                    <count group_id="O2" value="71"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60"/>
                    <measurement group_id="O2" value="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>The same methodology was used as the primary endpoint for each visit. The statistical analysis is presenting the Day 14 data.</non_inferiority_desc>
            <p_value>0.0006</p_value>
            <method>Farrington and Manning test</method>
            <param_type>lower 95% CI</param_type>
            <param_value>-0.05</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.05</ci_lower_limit>
            <ci_upper_limit>0.10</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit</title>
        <description>The proportion of subjects reaching antirabies antibody titer of ≥ LLOQ of the assay at each visit after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine.</description>
        <time_frame>Days 3, 5, 7, 14, 28, 49, and 140</time_frame>
        <population>Primary PK population (all subjects who receive the full dose of BPL HRIG or comparator HRIG and the first 3 doses of active rabies vaccine on Days 0, 3, 7 and for whom the PK sample at Day 14 is taken).</population>
        <group_list>
          <group group_id="O1">
            <title>BPL HRIG + RabAvert</title>
            <description>20 IU/kg dose HRIG + active rabies vaccine</description>
          </group>
          <group group_id="O2">
            <title>Comparator HyperRab + RabAvert</title>
            <description>20 IU/kg dose HRIG + active rabies vaccine</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit</title>
          <description>The proportion of subjects reaching antirabies antibody titer of ≥ LLOQ of the assay at each visit after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine.</description>
          <population>Primary PK population (all subjects who receive the full dose of BPL HRIG or comparator HRIG and the first 3 doses of active rabies vaccine on Days 0, 3, 7 and for whom the PK sample at Day 14 is taken).</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="73"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70"/>
                    <measurement group_id="O2" value="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="71"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71"/>
                    <measurement group_id="O2" value="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 49</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="72"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 140</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="62"/>
                    <count group_id="O2" value="71"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62"/>
                    <measurement group_id="O2" value="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>The same methodology was used as the primary endpoint for each visit. The statistical analysis is presenting the Day 14 data.</non_inferiority_desc>
            <p_value>0</p_value>
            <method>Farrington and Manning test</method>
            <param_type>lower 95% CI</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>For Day 14, all subjects achieved the endpoint (RVNA titer &gt; LLOQ). Since the statistic to measure the performance is a proportion, the proportion is 1 and no variance is calculable.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>RVNA Geometric Mean Titers at Days 14, 28, 49 and 140</title>
        <description>Comparison of the GMTs for antirabies antibody titer after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine to assess the inhibitory effects of BPL HRIG on active immunization relative to that of the comparator HRIG.</description>
        <time_frame>Days 14, 28, 49 and 140</time_frame>
        <population>Secondary PK population (subjects who receive the full dose of BPL HRIG or comparator HRIG and all 5 doses of active rabies vaccine and for whom all required PK samples are taken).</population>
        <group_list>
          <group group_id="O1">
            <title>BPL HRIG + RabAvert</title>
            <description>20 IU/kg dose HRIG + active rabies vaccine</description>
          </group>
          <group group_id="O2">
            <title>Comparator HyperRab + RabAvert</title>
            <description>20 IU/kg dose HRIG + active rabies vaccine</description>
          </group>
        </group_list>
        <measure>
          <title>RVNA Geometric Mean Titers at Days 14, 28, 49 and 140</title>
          <description>Comparison of the GMTs for antirabies antibody titer after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine to assess the inhibitory effects of BPL HRIG on active immunization relative to that of the comparator HRIG.</description>
          <population>Secondary PK population (subjects who receive the full dose of BPL HRIG or comparator HRIG and all 5 doses of active rabies vaccine and for whom all required PK samples are taken).</population>
          <units>IU/mL</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.30" lower_limit="10.15" upper_limit="14.90"/>
                    <measurement group_id="O2" value="8.38" lower_limit="6.54" upper_limit="10.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.18" lower_limit="8.39" upper_limit="12.34"/>
                    <measurement group_id="O2" value="7.78" lower_limit="6.26" upper_limit="9.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 49</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.91" lower_limit="8.94" upper_limit="13.32"/>
                    <measurement group_id="O2" value="7.78" lower_limit="6.34" upper_limit="9.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 140</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.72" lower_limit="2.21" upper_limit="3.34"/>
                    <measurement group_id="O2" value="2.02" lower_limit="1.62" upper_limit="2.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>20 weeks treatment</time_frame>
      <desc>Includes treatment emergent adverse events</desc>
      <group_list>
        <group group_id="E1">
          <title>BPL HRIG + RabAvert</title>
          <description>20 IU/kg dose HRIG + active rabies vaccine&#xD;
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.&#xD;
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.</description>
        </group>
        <group group_id="E2">
          <title>Comparator HyperRab + RabAvert</title>
          <description>20 IU/kg dose HRIG + active rabies vaccine&#xD;
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.&#xD;
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="81"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Vaccination site pain</sub_title>
                <description>Vaccination site pain AEs were related to the vaccine dose administration.</description>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="81"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="81"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="81"/>
                <counts group_id="E2" events="12" subjects_affected="10" subjects_at_risk="81"/>
              </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>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Head of Medical Affairs</name_or_title>
      <organization>Bio Products Laboratory</organization>
      <phone>1-844-4BPLUSA</phone>
      <email>MedInfo@bpl-us.com</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/NCT03264157
org study id: RIG01
nct id: NCT03264157
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
A prospective, randomized, blinded, parallel-group, non-inferiority, phase II/III study of
      the safety and effectiveness of simulated post-exposure prophylaxis with BPL HRIG with
      co-administration of active rabies vaccine in healthy subjects.
Each subject will undergo a total of 9 visits. Subjects' eligibility will be assessed at
      Screening, which can occur up to 28 days prior to dosing. Following a repeat eligibility
      check at Day 0, eligible subjects will be randomized and dosed with the randomized treatment
      (BPL HRIG + vaccine or Comparator HRIG + vaccine) on Day 0. Further assessments will be
      conducted on Days 3, 5, 7, 14, 28, 49 and the end of study assessment on Day 140. Vaccine
      will be administered on Day 0, 3, 7, 14 and 28.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Treatment A: BPL HRIG + active rabies vaccine Treatment B: Comparator HRIG + active rabies vaccine
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double-blind study
measure: Proportion of Subjects With Anti-rabies Antibody Titer of ≥0.5 IU/mL
time frame: Day 14
description: Non-inferiority in terms of the proportion of subjects with anti-rabies antibody titer of ≥0.5 IU/mL after study drug administration using a non-inferiority margin of 10%.
measure: Analysis of AUC0-7d
time frame: Day 0 to Day 7
description: The AUC0-7d for BPL HRIG and vaccine versus comparator HRIG and vaccine using a non inferiority margin of 20%.
measure: RVNA Geometric Mean Titers at Days 3, 5, 7 and 14
time frame: Days 3, 5, 7 and 14
description: Comparison of the geometric mean titers (GMTs) for antirabies antibody titer after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine. The median peak RVNA titer occurred at Day 14, which is reflected in the analysis. The RVNA titer to peak geometric mean is analyzed using a repeated measures analysis. The inferential test compares RVNA values between BPL HRIG and HyperRab in a single analysis across all visits at or below the visit at which peak titer is observed. The geometric mean values presented represent a mean across all visits from baseline through and including Day 14.
measure: Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit
time frame: Days 3, 5, 7, 14, 28, 49, and 140
description: The proportion of subjects reaching antirabies antibody titer of ≥ 0.5 IU/mL after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine.
measure: Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit
time frame: Days 3, 5, 7, 14, 28, 49, and 140
description: The proportion of subjects reaching antirabies antibody titer of ≥ LLOQ of the assay at each visit after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine.
measure: RVNA Geometric Mean Titers at Days 14, 28, 49 and 140
time frame: Days 14, 28, 49 and 140
description: Comparison of the GMTs for antirabies antibody titer after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine to assess the inhibitory effects of BPL HRIG on active immunization relative to that of the comparator HRIG.
arm group label: BPL HRIG + RabAvert
arm group type: Experimental
description: 20 IU/kg dose HRIG + active rabies vaccine
arm group label: Comparator HyperRab + RabAvert
arm group type: Active Comparator
description: 20 IU/kg dose HRIG + active rabies vaccine
intervention type: Drug
intervention name: HRIG
description: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.
arm group label: BPL HRIG + RabAvert
intervention type: Drug
intervention name: HyperRAB
description: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.
arm group label: Comparator HyperRab + RabAvert
other name: HRIG
intervention type: Biological
intervention name: RabAvert
description: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
arm group label: BPL HRIG + RabAvert
arm group label: Comparator HyperRab + RabAvert
other name: active rabies vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Elizabeth Holmes, MD
role: Study Director
affiliation: Bio Products Laboratory
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Rabies
mesh term: Vaccines
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 