<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/NCT01667341</url>
  </required_header>
  <id_info>
    <org_study_id>GEN-003-001</org_study_id>
    <nct_id>NCT01667341</nct_id>
  </id_info>
  <brief_title>Safety and Immunogenicity Study of Therapeutic HSV-2 Vaccine</brief_title>
  <official_title>A Phase I/IIa, Randomized, Double-blind, Dose-ranging, Placebo-controlled Study of the Safety and Immunogenicity of a HSV-2 Vaccine Containing Matrix M-2 Adjuvant in Individuals With Documented Genital HSV-2 Genital Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genocea Biosciences, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Genocea Biosciences, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomized, double-blind, placebo-controlled, dose escalation study. There will be 3 cohorts&#xD;
      of patients defined by the antigen dose (10, 30 or 100 µg of each antigen), and within each&#xD;
      cohort, patients will be randomized at a ratio of 3:1:1 to one of the following:&#xD;
&#xD;
        1. GEN-003/M2: GEN-003 plus Matrix M-2 adjuvant (50 µg per dose)&#xD;
&#xD;
        2. GEN-003: Antigens alone&#xD;
&#xD;
        3. Placebo (DPBS diluent)&#xD;
&#xD;
      Each Cohort is divided into 2 Groups. For each dose cohort, immunizations begin with a Pilot&#xD;
      Group. Immunization of the remainder of the Group &quot;Continuation Group&quot;) is contingent upon&#xD;
      successful review of data from the Pilot Group through Day 7 after immunization. Dose&#xD;
      escalation to the next dose level Cohort proceeds after evaluation of safety data from all&#xD;
      patients in the prior Cohort and only after all specified safety criteria are met. The total&#xD;
      numbers of patients in each Group and Cohort are as follows:&#xD;
&#xD;
        -  10 µg Cohort: 10 Pilot Group, 40 Continuation Group (50 Total)&#xD;
&#xD;
        -  30 µg Cohort: 10 Pilot Group, 40 Continuation Group (50 Total)&#xD;
&#xD;
        -  100 µg Cohort: 10 Pilot Group, 40 Continuation Group (50 Total)&#xD;
&#xD;
        -  Totals per group: 30 Pilot Group, 120 Continuation Group (150 Total Patients)&#xD;
&#xD;
      Subjects will receive 3 doses of the assigned treatment (GEN-003/M-2, GEN-003, or placebo) at&#xD;
      3 week intervals. Sampling from mucocutaneous genital sites for viral shedding will be done&#xD;
      twice daily for 28 days prior to the first immunization (baseline shedding), and again&#xD;
      following the last immunization. Follow-up for safety monitoring will be conducted for 12&#xD;
      months after the last immunization.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2012</start_date>
  <completion_date type="Actual">May 9, 2014</completion_date>
  <primary_completion_date type="Actual">May 9, 2014</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with adverse events as a measure of safety and tolerability</measure>
    <time_frame>57 Weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity measured by humoral (antibody) and T-cell responses to vaccine antigens</measure>
    <time_frame>33 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in proportion of days with detectable viral shedding</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">143</enrollment>
  <condition>Genital Herpes Simplex Type 2</condition>
  <arm_group>
    <arm_group_label>Low Dose GEN-003 with Matrix M-2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10µg GEN-003, 50µg Matrix M-2 Adjuvant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mid Dose GEN-003 with Matrix M-2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30µg GEN-003, 50µg Matrix M-2 Adjuvant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Dose GEN-003 with Matrix M-2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100µg GEN-003, 50µg Matrix M-2 Adjuvant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Dose GEN-003 Only</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10µg GEN-003</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mid Dose GEN-003 Only</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30µg GEN-003</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Dose GEN-003 Only</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100µg GEN-003</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0.5 mL phosphate buffered saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>GEN-003 with Matrix M-2</intervention_name>
    <description>IM administration of GEN-003 Vaccine with 50ug Matrix M-2 Adjuvant.</description>
    <arm_group_label>High Dose GEN-003 with Matrix M-2</arm_group_label>
    <arm_group_label>Low Dose GEN-003 with Matrix M-2</arm_group_label>
    <arm_group_label>Mid Dose GEN-003 with Matrix M-2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>GEN-003</intervention_name>
    <description>IM administration of GEN-003 Vaccine, antigens alone (without adjuvant).</description>
    <arm_group_label>High Dose GEN-003 Only</arm_group_label>
    <arm_group_label>Low Dose GEN-003 Only</arm_group_label>
    <arm_group_label>Mid Dose GEN-003 Only</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>IM administration of 0.5 mL dose of Dulbecco's phosphate buffered saline.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>PBS</other_name>
    <other_name>DPBS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women ages 18 to 50 years, inclusive.&#xD;
&#xD;
          -  Willing to practice a highly effective method of contraception that includes the use&#xD;
             of a barrier method such as a condom.&#xD;
&#xD;
          -  Diagnosis of genital HSV-2 infection for &gt; 1 year supported by ONE of the following&#xD;
             documented in the medical history or performed at screening:&#xD;
&#xD;
               -  Western blot for HSV-2&#xD;
&#xD;
               -  Type-specific polymerase chain reaction (PCR) or viral culture&#xD;
&#xD;
               -  Compatible clinical history AND HSV-2 ELISA (HerpSelect) index value &gt;3.5&#xD;
&#xD;
          -  A history of at least 3 and no more than 9 reported clinical occurrences in the prior&#xD;
             12 months, or, if currently on suppressive therapy, history of at least 3 and no more&#xD;
             than 9 reported clinical occurrences in the 12 months prior to initiation suppressive&#xD;
             therapy.&#xD;
&#xD;
          -  Good general health status as determined by screening evaluation completed within 90&#xD;
             days prior to immunization. Any out of range screening clinical laboratory values&#xD;
             should be considered not clinically significant by the Investigator.&#xD;
&#xD;
          -  Patient has provided written informed consent.&#xD;
&#xD;
          -  Ability and willingness to perform and comply with all study procedures including&#xD;
             attending clinic visits as scheduled. Note: patients must provide, by the day of&#xD;
             randomization, a minimum of 28 (equivalent of 14 days) baseline viral swab samples to&#xD;
             continue to be eligible and be randomized).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  On suppressive antiviral medication within 7 days of baseline viral shedding&#xD;
             evaluation.&#xD;
&#xD;
          -  Immunocompromised individuals, including those receiving systemic corticosteroids or&#xD;
             other immunosuppressive agents.&#xD;
&#xD;
          -  Positive serologic test for HIV-1 infection; positive hepatitis B surface antigen&#xD;
             (HBsAg) or antibody for hepatitis C (anti-HCV).&#xD;
&#xD;
          -  Active lesions consistent with herpetic disease at the time of scheduled immunization.&#xD;
&#xD;
          -  Pregnant or nursing women.&#xD;
&#xD;
          -  Receipt of any investigational drug within 30 days of the first scheduled day of&#xD;
             immunization.&#xD;
&#xD;
          -  History of hypersensitivity to any component of the vaccine.&#xD;
&#xD;
          -  History of genital HSV-1 infection.&#xD;
&#xD;
          -  History of: (1) any form of ocular HSV infection, (2) HSV-related erythema multiforme,&#xD;
             or (3) herpes meningitis or encephalitis.&#xD;
&#xD;
          -  Any other condition which in the opinion of the Investigator would interfere with the&#xD;
             successful completion of the study protocol.&#xD;
&#xD;
          -  History of drug or alcohol abuse that, in the opinion of the Investigator, would&#xD;
             interfere with the patient's ability to comply with the requirements of the study.&#xD;
&#xD;
          -  Prior immunization with a vaccine containing HSV-2 antigens.&#xD;
&#xD;
          -  Receipt of blood products within 90 days of the first immunization.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Alabama Vaccine Research Unit</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294-0006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Infectious Disease Research</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229-3039</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westover Heights Clinic</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Clinical Studies - Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Clinical Studies - Clear Lake/Webster</name>
      <address>
        <city>Webster</city>
        <state>Texas</state>
        <zip>77598</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UW Virology Research Clinic</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <disposition_first_submitted>December 1, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>December 1, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">December 30, 2015</disposition_first_posted>
  <last_update_submitted>May 30, 2018</last_update_submitted>
  <last_update_submitted_qc>May 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HSV</keyword>
  <keyword>Herpes</keyword>
  <keyword>genital infection</keyword>
  <keyword>vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Herpes Simplex</mesh_term>
    <mesh_term>Herpes Genitalis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT01667341
org study id: GEN-003-001
nct id: NCT01667341
lead sponsor: 
has dmc: Yes
Randomized, double-blind, placebo-controlled, dose escalation study. There will be 3 cohorts
      of patients defined by the antigen dose (10, 30 or 100 µg of each antigen), and within each
      cohort, patients will be randomized at a ratio of 3:1:1 to one of the following:

        1. GEN-003/M2: GEN-003 plus Matrix M-2 adjuvant (50 µg per dose)

        2. GEN-003: Antigens alone

        3. Placebo (DPBS diluent)

      Each Cohort is divided into 2 Groups. For each dose cohort, immunizations begin with a Pilot
      Group. Immunization of the remainder of the Group "Continuation Group") is contingent upon
      successful review of data from the Pilot Group through Day 7 after immunization. Dose
      escalation to the next dose level Cohort proceeds after evaluation of safety data from all
      patients in the prior Cohort and only after all specified safety criteria are met. The total
      numbers of patients in each Group and Cohort are as follows:

        -  10 µg Cohort: 10 Pilot Group, 40 Continuation Group (50 Total)

        -  30 µg Cohort: 10 Pilot Group, 40 Continuation Group (50 Total)

        -  100 µg Cohort: 10 Pilot Group, 40 Continuation Group (50 Total)

        -  Totals per group: 30 Pilot Group, 120 Continuation Group (150 Total Patients)

      Subjects will receive 3 doses of the assigned treatment (GEN-003/M-2, GEN-003, or placebo) at
      3 week intervals. Sampling from mucocutaneous genital sites for viral shedding will be done
      twice daily for 28 days prior to the first immunization (baseline shedding), and again
      following the last immunization. Follow-up for safety monitoring will be conducted for 12
      months after the last immunization.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Number of patients with adverse events as a measure of safety and tolerability
time frame: 57 Weeks
measure: Immunogenicity measured by humoral (antibody) and T-cell responses to vaccine antigens
time frame: 33 weeks
measure: Change in proportion of days with detectable viral shedding
time frame: 6 weeks
arm group label: Low Dose GEN-003 with Matrix M-2
arm group type: Experimental
description: 10µg GEN-003, 50µg Matrix M-2 Adjuvant
arm group label: Mid Dose GEN-003 with Matrix M-2
arm group type: Experimental
description: 30µg GEN-003, 50µg Matrix M-2 Adjuvant
arm group label: High Dose GEN-003 with Matrix M-2
arm group type: Experimental
description: 100µg GEN-003, 50µg Matrix M-2 Adjuvant
arm group label: Low Dose GEN-003 Only
arm group type: Experimental
description: 10µg GEN-003
arm group label: Mid Dose GEN-003 Only
arm group type: Experimental
description: 30µg GEN-003
arm group label: High Dose GEN-003 Only
arm group type: Experimental
description: 100µg GEN-003
arm group label: Placebo
arm group type: Placebo Comparator
description: 0.5 mL phosphate buffered saline
intervention type: Biological
intervention name: GEN-003 with Matrix M-2
description: IM administration of GEN-003 Vaccine with 50ug Matrix M-2 Adjuvant.
arm group label: High Dose GEN-003 with Matrix M-2
arm group label: Low Dose GEN-003 with Matrix M-2
arm group label: Mid Dose GEN-003 with Matrix M-2
intervention type: Biological
intervention name: GEN-003
description: IM administration of GEN-003 Vaccine, antigens alone (without adjuvant).
arm group label: High Dose GEN-003 Only
arm group label: Low Dose GEN-003 Only
arm group label: Mid Dose GEN-003 Only
intervention type: Biological
intervention name: Placebo
description: IM administration of 0.5 mL dose of Dulbecco's phosphate buffered saline.
arm group label: Placebo
other name: PBS
other name: DPBS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Herpes Simplex
mesh term: Herpes Genitalis