<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/NCT03038243</url>
  </required_header>
  <id_info>
    <org_study_id>VAC-047</org_study_id>
    <nct_id>NCT03038243</nct_id>
  </id_info>
  <brief_title>Safety, Immunogenicity and Efficacy Study of Inactivated Whole Cell Shigella Flexneri 2a Vaccine With and Without dmLT in Adults</brief_title>
  <official_title>A Phase 2a/2b, Randomized, Double-blinded, Placebo-controlled, Trial to Assess the Safety, Immunogenicity and Efficacy of Inactivated Shigella Flexneri 2a Whole Cell (Sf2aWC) Vaccine Administered With and Without Double Mutant E. Coli Heat Labile Toxin (dmLT) in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PATH</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>PATH</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This is a research study about an experimental (investigational) oral inactivated whole cell&#xD;
      Shigella flexneri 2a killed vaccine (Sf2aWC) and an adjuvant called dmLT. Sf2aWC is a killed&#xD;
      vaccine that is being made to prevent disease from Shigella., which causes bloody, watery&#xD;
      diarrhea. An adjuvant is something that is added to a vaccine to make it work better. The&#xD;
      purpose of the study is to see if the vaccine will protect people from Shigella infection&#xD;
      with or without an adjuvant called dmLT. About 72 healthy adults, ages 18-45, will&#xD;
      participate in this study. The study will compare 2 different vaccination groups and 1&#xD;
      control group. Volunteers have an equal chance to be in any of the 3 groups. Study procedures&#xD;
      include: stool samples, blood samples and documenting side effects. Participants will be&#xD;
      involved in study related procedures for about 6 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite the public health burden of Shigella spp. on travelers, deployed soldiers and, most&#xD;
      significantly, young children in the developing world, there is no licensed vaccine against&#xD;
      Shigella. The rationale for using Shigella flexneri 2a whole cell killed vaccine (Sf2aWC), is&#xD;
      that it is expected to be especially well tolerated by subjects. This is a single site,&#xD;
      2a/2b, double-blind, randomized, placebo-controlled, study in healthy adult subjects.&#xD;
      Approximately 72 subjects will be enrolled into one of three vaccination groups: Sf2aWC 1011&#xD;
      Sf2aWC cells plus 10 µg dmLT (Group 1, n=24), 1011 Sf2WC cells alone (Group 2, n=24); or&#xD;
      placebo (Group 4, n=24). The placebo preparation will be bicarbonate buffer.&#xD;
&#xD;
      After the vaccination phase subjects will be admitted by cohort on day 84 to an inpatient&#xD;
      facility for 12 days to undergo challenge with approximately 1500 colony forming units (CFU)&#xD;
      of wild type S. flexneri 2a strain 2457T (administered with NaHCO3 buffer). After 5 days of&#xD;
      observation for clinical endpoints (or earlier and within 12 hours if they meet the&#xD;
      definition of moderate-to-severe shigellosis as defined in the primary endpoints section&#xD;
      below), subjects will receive a 5-day course of orally administered ciprofloxacin.&#xD;
&#xD;
      The primary objective of this study are to 1) evaluate, the safety and reactogenicity of 3&#xD;
      oral sequential doses of Sf2aWC with or without dmLT, 2) To measure the protective efficacy&#xD;
      of 3 spaced doses of high-dose Sf2aWC vaccine with and without dmLT against&#xD;
      moderate-to-severe shigellosis following experimental oral challenge with wild-type S.&#xD;
      flexneri 2a 2457T&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of funding&#xD;
  </why_stopped>
  <start_date type="Anticipated">August 1, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2018</primary_completion_date>
  <phase>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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>solicited reactions, AEs, SAEs</measure>
    <time_frame>first vaccination through 6 months post-3rd vaccination</time_frame>
    <description>solicited reactions, AEs, SAEs assessed post-vaccination using targeted physical examinations, vital signs, and clinical laboratory tests</description>
  </primary_outcome>
  <primary_outcome>
    <measure>prevention of moderate to severe shigellosis</measure>
    <time_frame>up to 24 hours</time_frame>
    <description>prevention of moderate to severe shigellosis identified by diarrhea, fever, dysentery, and other signs/symptoms of enteric illness</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Shigella Sonnei Dysenteries</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT)</intervention_name>
    <description>2.25 x 10^11 Sf2aWC cells +10 µg dmLT administered orally on Days 0, 28, and 56</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Shigella flexneri 2a whole cell (Sf2aWC) vaccine</intervention_name>
    <description>2.25 x 10^11 Sf2WC cells administered orally on Days 0, 28, and 56</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>2.0 grams of NaHCO3 dissolved in 150 mL of sterile water</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy adults, male or female, age 18 to 45 years (inclusive) at the time of&#xD;
             enrollment.&#xD;
&#xD;
          2. General good health, without clinically significant medical history, physical&#xD;
             examination findings or clinical laboratory abnormalities per clinical judgment of PI.&#xD;
&#xD;
          3. Willingness to participate in the study after all aspects of the protocol have been&#xD;
             explained and written informed consent obtained.&#xD;
&#xD;
          4. Completion of a training session and demonstrated comprehension of the protocol&#xD;
             procedures and knowledge of Shigella associated illness by passing a written&#xD;
             examination (70% pass score).&#xD;
&#xD;
          5. Availability for the study duration, including all planned follow-up visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of a significant medical or psychiatric condition that in the opinion of the&#xD;
             investigator precludes participation in the study. Some medical conditions that are&#xD;
             adequately treated and stable would not preclude entry into the study. These&#xD;
             conditions might include stable asthma controlled with inhalers or mild hypertension&#xD;
             stably controlled with a single agent.&#xD;
&#xD;
          2. Significant abnormalities in screening hematology, or serum chemistry as determined by&#xD;
             PI or PI in consultation with the Medical Officer and sponsor.&#xD;
&#xD;
          3. Recent of a non-study vaccine or receipt of another investigational product (within 14&#xD;
             days before vaccination).&#xD;
&#xD;
          4. Have household contacts who are &lt;3 years old or &gt;70 years old or infirm or&#xD;
             immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer&#xD;
             chemotherapy, or other chronic debilitating disease).&#xD;
&#xD;
          5. Use of any medication that affects the immune function (e.g., corticosteroids and&#xD;
             others) within 30 days preceding the first vaccination or planned use during the&#xD;
             active study period.&#xD;
&#xD;
          6. Symptoms of Traveler's diarrhea associated with travel to countries where Shigella or&#xD;
             other enteric infections are endemic (most of the developing world) within 1 year&#xD;
             prior to dosing.&#xD;
&#xD;
          7. History of shigellosis or Shigella vaccination or challenge or a laboratory worker&#xD;
             with known exposure to Shigella within the last 6 months&#xD;
&#xD;
          8. Prior receipt of experimental Shigella vaccine or live Shigella challenge within 3&#xD;
             years.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wilbur Chen, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Maryland School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Vaccine Development (CVD), University of Maryland School of Medicine</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>January 23, 2017</study_first_submitted>
  <study_first_submitted_qc>January 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>November 16, 2017</last_update_submitted>
  <last_update_submitted_qc>November 16, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Shigella</keyword>
  <keyword>vaccine</keyword>
  <keyword>shigellosis</keyword>
  <keyword>dysentery</keyword>
  <keyword>whole cell</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dysentery, Bacillary</mesh_term>
    <mesh_term>Dysentery</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03038243
org study id: VAC-047
nct id: NCT03038243
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a research study about an experimental (investigational) oral inactivated whole cell
      Shigella flexneri 2a killed vaccine (Sf2aWC) and an adjuvant called dmLT. Sf2aWC is a killed
      vaccine that is being made to prevent disease from Shigella., which causes bloody, watery
      diarrhea. An adjuvant is something that is added to a vaccine to make it work better. The
      purpose of the study is to see if the vaccine will protect people from Shigella infection
      with or without an adjuvant called dmLT. About 72 healthy adults, ages 18-45, will
      participate in this study. The study will compare 2 different vaccination groups and 1
      control group. Volunteers have an equal chance to be in any of the 3 groups. Study procedures
      include: stool samples, blood samples and documenting side effects. Participants will be
      involved in study related procedures for about 6 months.
Despite the public health burden of Shigella spp. on travelers, deployed soldiers and, most
      significantly, young children in the developing world, there is no licensed vaccine against
      Shigella. The rationale for using Shigella flexneri 2a whole cell killed vaccine (Sf2aWC), is
      that it is expected to be especially well tolerated by subjects. This is a single site,
      2a/2b, double-blind, randomized, placebo-controlled, study in healthy adult subjects.
      Approximately 72 subjects will be enrolled into one of three vaccination groups: Sf2aWC 1011
      Sf2aWC cells plus 10 µg dmLT (Group 1, n=24), 1011 Sf2WC cells alone (Group 2, n=24); or
      placebo (Group 4, n=24). The placebo preparation will be bicarbonate buffer.

      After the vaccination phase subjects will be admitted by cohort on day 84 to an inpatient
      facility for 12 days to undergo challenge with approximately 1500 colony forming units (CFU)
      of wild type S. flexneri 2a strain 2457T (administered with NaHCO3 buffer). After 5 days of
      observation for clinical endpoints (or earlier and within 12 hours if they meet the
      definition of moderate-to-severe shigellosis as defined in the primary endpoints section
      below), subjects will receive a 5-day course of orally administered ciprofloxacin.

      The primary objective of this study are to 1) evaluate, the safety and reactogenicity of 3
      oral sequential doses of Sf2aWC with or without dmLT, 2) To measure the protective efficacy
      of 3 spaced doses of high-dose Sf2aWC vaccine with and without dmLT against
      moderate-to-severe shigellosis following experimental oral challenge with wild-type S.
      flexneri 2a 2457T
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: solicited reactions, AEs, SAEs
time frame: first vaccination through 6 months post-3rd vaccination
description: solicited reactions, AEs, SAEs assessed post-vaccination using targeted physical examinations, vital signs, and clinical laboratory tests
measure: prevention of moderate to severe shigellosis
time frame: up to 24 hours
description: prevention of moderate to severe shigellosis identified by diarrhea, fever, dysentery, and other signs/symptoms of enteric illness
arm group label: Cohort 1
arm group type: Experimental
description: Group 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water
arm group label: Cohort 2
arm group type: Experimental
description: Group 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water
arm group label: Cohort 3
arm group type: Experimental
description: Group 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water
intervention type: Biological
intervention name: Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT)
description: 2.25 x 10^11 Sf2aWC cells +10 µg dmLT administered orally on Days 0, 28, and 56
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
intervention type: Biological
intervention name: Shigella flexneri 2a whole cell (Sf2aWC) vaccine
description: 2.25 x 10^11 Sf2WC cells administered orally on Days 0, 28, and 56
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
intervention type: Other
intervention name: Placebo
description: 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Wilbur Chen, MD, MS
role: Principal Investigator
affiliation: University of Maryland School of Medicine
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dysentery, Bacillary
mesh term: Dysentery
mesh term: Vaccines
sharing ipd: No