<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/NCT04453293</url>
  </required_header>
  <id_info>
    <org_study_id>2019-01</org_study_id>
    <secondary_id>BAA 170090</secondary_id>
    <nct_id>NCT04453293</nct_id>
  </id_info>
  <brief_title>Immunization With BCG Vaccine to Prevent Tuberculosis Infection</brief_title>
  <acronym>TIPI</acronym>
  <official_title>A Proof-of Concept, Randomized, Controlled Study of Tuberculosis Immunization With BCG to Prevent Infection in Healthy Adults (TIPI Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Henry M. Jackson Foundation for the Advancement of Military Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United States Department of Defense</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Uniformed Services University of the Health Sciences</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Henry M. Jackson Foundation for the Advancement of Military Medicine</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>
      The purpose of this research is to find out if a single dose of pre-travel vaccination with&#xD;
      BCG can lessen tuberculosis (TB) infection by producing an immune response when given to&#xD;
      adults traveling to countries with a high burden of TB. BCG will be compared with a placebo&#xD;
      (an inactive vaccine). BCG (Japan) is used globally but is not approved for use in the United&#xD;
      States, therefore it is considered experimental. Participants choosing to take part in this&#xD;
      research study, will be randomly assigned (this is like a coin flip) to BCG or placebo. 2000&#xD;
      eligible volunteers will be enrolled.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a multi-center, prospective, randomized, placebo-controlled, participant and&#xD;
      laboratory-blinded clinical trial to evaluate a single pre-travel vaccination with&#xD;
      investigational freeze-dried glutamate BCG (Japan) to prevent Mycobacterium tuberculosis&#xD;
      complex (Mtb) infection in healthy adult travelers, 18-65 years of age, exposed to persons&#xD;
      with TB in high burden countries.&#xD;
&#xD;
      The goals of this study are both public health and scientific. The public health goal of this&#xD;
      study is to offer possible protection against TB to US workers traveling abroad to work in&#xD;
      countries with a high burden of TB where there is a risk for multidrug resistant/extensively&#xD;
      drug resistant TB exposure and where effective TB infection control interventions are&#xD;
      infrequently fully implemented. A long-term scientific goal is to test the hypothesis that TB&#xD;
      vaccination prevents primary TB infection as measured by peripheral blood TB interferon gamma&#xD;
      release assay (IGRA) conversion at return from travel visit, as well as sustained conversion&#xD;
      at approximately 4-6 months post-return from travel. Rates of IGRA conversion in&#xD;
      BCG-vaccinated recipients as compared to placebo recipients will be evaluated. Additionally,&#xD;
      this study will collect information regarding exposure to and infection with TB, assessing&#xD;
      risk factors for TB infection during the participant's travel.&#xD;
&#xD;
      This study will recruit two types of travelers: Type 1 travelers (Short-term travelers) that&#xD;
      will be limited to health care workers traveling for 4 weeks, but less than 6 months and Type&#xD;
      2 travelers (Long-term travelers) that will include those planning to reside in the country&#xD;
      for 6 months or more (but ≤ 2.5 years duration), regardless of occupational group.&#xD;
&#xD;
      High TB burden countries for this study are defined as countries identified in the World&#xD;
      Health Organization (WHO) Global Tuberculosis Report 2020 to have a TB incidence of&#xD;
      ≥70/100,000. Targeted participant population of travelers at-risk for high TB exposure will&#xD;
      work specifically in one or more of the 74 highest ranked TB burden countries as recognized&#xD;
      by the WHO 2020 report.&#xD;
&#xD;
      Participants enrolled will be required to complete typically 4, but up to 6 study visits&#xD;
      composed of: screening and eligibility assessments, vaccination with study vaccine (BCG or&#xD;
      placebo), a subsequent post-vaccination follow-up assessment visit to identify potential&#xD;
      adverse event occurrences, a post-travel follow-up visit to assess the risk factors for Mtb&#xD;
      infection and assess the primary endpoint (IGRA conversion from negative to positive), and if&#xD;
      applicable, an additional visit for those participants who are found to have a borderline&#xD;
      IGRA result. For participants found to have post-travel IGRA conversion results, an&#xD;
      additional visit will be requested for assessment of sustained TB IGRA conversion and&#xD;
      reversion.&#xD;
&#xD;
      Different evaluations, tests and/or procedures to be performed during study visits include:&#xD;
      interviews relevant to their medical history and general well-being between study visits;&#xD;
      physical examinations and vital signs; completion of a pre-travel questionnaire and&#xD;
      post-travel questionnaires to collect information regarding exposure to TB and risk factors&#xD;
      for infection, as well as any information regarding development of active TB disease, both&#xD;
      pulmonary and/or extrapulmonary and evaluation for the presence and severity of self-reported&#xD;
      symptomatic all-cause respiratory infection occurrences while traveling abroad; keeping a&#xD;
      record to assess for occurrence of local reactions at the injection site and incidence of&#xD;
      selected symptoms for the first 14 days post-vaccination; and blood draws (2 up to 4&#xD;
      depending on what previous blood test results reveal).&#xD;
&#xD;
      The study design is endpoint driven; designed to observe 56 total IGRA conversions.&#xD;
      Therefore, enrollment into this study will be stopped if the target endpoint (56 IGRA&#xD;
      conversions) are met earlier than expected.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 1, 2021</start_date>
  <completion_date type="Anticipated">May 14, 2025</completion_date>
  <primary_completion_date type="Anticipated">May 14, 2025</primary_completion_date>
  <phase>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>Randomized, controlled trial of BCG (Tokyo 172) vaccine single dose given intradermally compared to placebo vaccine (diluent) given intradermally single dose</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>The participant and the laboratory (endpoint measurement) will be masked</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in TB IGRA blood test results from baseline pre-travel and post-travel return</measure>
    <time_frame>At baseline, and 4-10 weeks post-travel return</time_frame>
    <description>Conversion change of TB IGRA from pre-travel baseline value of negative to positive post-travel, using FDA-approved breakpoints as a measure of Mycobacterium tuberculosis infection. Response will be assessed using technology of the T-SPOT.TB test method. Specifically, the test measures the number of spots from T cells sensitized to TB infection on a plate containing 4 different antigens: nil (negative control), 2 TB antigens (ESAT-6 and CFP-10, also called Panel A and Panel B), and phytohemagglutinin (positive control). Results are interpreted by subtracting the spot count in the negative (NIL) control from the spot count in Panels A and B:&#xD;
Positive ≥ 8 spots&#xD;
Negative ≤ 4 spots&#xD;
Borderline 5, 6, or 7 spots&#xD;
Invalid</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with sustained conversion and reversion in the TB IGRA converters</measure>
    <time_frame>4-6 months from return post-travel</time_frame>
    <description>Participants identified as having positive TB IGRA blood test results will undergo a TB IGRA re-test to determine sustained (positive result) conversion and reversion (defined as negative/borderline) using the T-SPOT.TB test method. The rate of conversion for each study group will be calculated as the number of conversions divided by person-months of travel</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with history of TB disease/symptoms while deployed</measure>
    <time_frame>Through final IGRA testing, expected average time 4-10 weeks post-travel return</time_frame>
    <description>Participants with response of symptoms suggestive of TB disease (i.e., bloody cough, cough ≥ 2 weeks, chest pain, fever ≥ 2 weeks, night sweats, and unintentional weight loss), development of active TB disease (possible, probable, or definite) and TB treatment that may have occurred during travel to high burden TB country or up to the time of IGRA testing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identify potential risk factors for Mtb infection in the targeted study population collected on Post-Travel Questionnaire</measure>
    <time_frame>Through final IGRA testing, expected average time 4-10 weeks post-travel return</time_frame>
    <description>Questionnaire responses from participants after travel will collect information regarding exposure to TB and risk factors for infection, as well as any information regarding risk reduction activities taken (i.e. personal protective measures) that may have occurred during travel to countries with high burden TB identified in the 2014 World Health Organization (WHO) TB report. Travelers will be asked if they had contact with anyone known to have TB disease or if they worked with populations at risk for HIV while abroad. They will also be asked about accommodations, daily routine, and if they used public transportation such as mini-buses and if so, how frequently. A final open-ended question e.g., &quot;Do you have reason to believe you were exposed?&quot; will be asked of all travelers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with treatment-related adverse effects following intradermal administration of BCG vaccine</measure>
    <time_frame>Baseline (pre-administration of vaccine), within 30 minutes of vaccination, 14-days post-vaccination, and 2 to 6 weeks post-vaccination (Visit 3)</time_frame>
    <description>Post-vaccination response to assess for occurrence of selected local injection site reactions (pain/tenderness, redness, ulceration, drainage, vesicle [blister], induration [swelling] and scarring), axillary/ cervical lymphadenopathy, and selected systemic symptoms (fever, headache, chills, dizziness, tiredness, nausea, gastrointestinal problems, rash, muscle and joint pain and general well-being) using the 2007 U.S. FDA guidance Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. For each reaction, the highest grade will be determined for each traveler. Participants will be provided with a memory aid card to record any occurrences of selected local reactions and systemic symptoms that may occur during the first 14-days post-vaccination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with self-reported symptoms of all-cause respiratory infections acquired while traveling abroad</measure>
    <time_frame>Through final IGRA testing, expected average time 4-10 weeks post-travel return</time_frame>
    <description>Questionnaire responses obtained from participants will assess self-reported symptomatic all-cause respiratory infection symptoms in five domains (nose, throat, chest, systemic, neurological) for presence, frequency of occurrence and severity, impact of acute symptoms on functional activities or productivity, and medical care encounters and treatment as a result of respiratory illness while traveling abroad.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">2000</enrollment>
  <condition>Tuberculosis Infection</condition>
  <arm_group>
    <arm_group_label>BCG vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Freeze-dried Glutamate Bacillus Calmette-Guérin (BCG) (Tokyo 172) vaccine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Vaccine diluent [sodium glutamate]</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BCG (Tokyo 172) vaccine</intervention_name>
    <description>Freeze-Dried Glutamate Bacillus Calmette-Guérin BCG Vaccine (Japan BCG Laboratory), 0.1 mL given as single dose by intradermal injection over the outer lower aspect of the deltoid region</description>
    <arm_group_label>BCG vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo vaccine diluent, 0.1 mL given as single dose by intradermal injection over the outer lower aspect of the deltoid region</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>sodium glutamate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants will be eligible for study participation if they meet all of the&#xD;
             following criteria:&#xD;
&#xD;
               1. Participant is willing to participate in the study as evidenced by providing&#xD;
                  voluntary written informed consent and Health Insurance Portability and&#xD;
                  Accountability Act (HIPAA) authorization prior to conducting any trial related&#xD;
                  procedures&#xD;
&#xD;
               2. Participant is male or female, age ≥ 18 years and ≤ 65 years at time of consent&#xD;
&#xD;
               3. Participant is in good general health, confirmed by medical history, laboratory&#xD;
                  screening, and physical examination&#xD;
&#xD;
               4. Participant has no known history of Mtb infection&#xD;
&#xD;
               5. Participant has no prior history of BCG vaccination, or previous receipt of an&#xD;
                  investigational Mtb vaccine&#xD;
&#xD;
               6. Participant is assessed to be at risk for TB exposure (particularly drug&#xD;
                  resistant TB) during planned travel and has planned to work in high TB burden&#xD;
                  countries for a duration of &gt;4 weeks and &lt;6 months for HCW, or ≥6 months and ≤2.5&#xD;
                  years if long term traveler and/or/HCW&#xD;
&#xD;
               7. Participant presents at least 4 weeks prior to travel departure&#xD;
&#xD;
               8. Participant is willing to forego any periodic tuberculin skin test screening&#xD;
                  procedures for 6 months after receiving BCG/placebo vaccine&#xD;
&#xD;
               9. Participant is willing to wait after receiving a COVID-19 vaccine for 7 days&#xD;
                  before receiving BCG/placebo vaccine&#xD;
&#xD;
              10. Participant is willing to complete all study visits as required by the protocol&#xD;
                  and is reachable by telephone or email during the study&#xD;
&#xD;
              11. Participant agrees to medical record access for purposes of relevant medical&#xD;
                  history collection&#xD;
&#xD;
                  For Females of Childbearing Potential Only:&#xD;
&#xD;
              12. Participant has a negative urine pregnancy test prior to starting study treatment&#xD;
&#xD;
              13. Participant is willing to use effective contraception for at least 30 days before&#xD;
                  and 6 weeks after BCG/placebo vaccination&#xD;
&#xD;
              14. Lactating female that is willing to refrain from breast-feeding for 6 weeks&#xD;
                  post-vaccination&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants will be ineligible for study participation if they meet any of the&#xD;
             following criteria:&#xD;
&#xD;
               1. Participant has known positive tuberculin skin test (&gt;10 mm) or positive IGRA&#xD;
&#xD;
               2. Participant has medical condition for which BCG vaccination is contraindicated&#xD;
                  (e.g., HIV or other immunocompromised conditions)&#xD;
&#xD;
               3. Participant is currently receiving (within last 30 days) immune-compromising&#xD;
                  treatments, such as TNF-α blockade&#xD;
&#xD;
               4. Participant has history of chronic (≥ 30 days) oral steroid use or intravenous&#xD;
                  (IV) steroids within the last 90 days&#xD;
&#xD;
               5. Participant has received radiation therapy or chemotherapy within the last 180&#xD;
                  days&#xD;
&#xD;
               6. Participant has received BCG treatment for bladder cancer&#xD;
&#xD;
               7. Participant is female and is pregnant (as defined by positive urine βHCG test) or&#xD;
                  intends to become pregnant in next 3 months, or is breast-feeding at screening or&#xD;
                  vaccination visit&#xD;
&#xD;
               8. Participant is unwilling to complete all required study elements (e.g., HIV&#xD;
                  testing)&#xD;
&#xD;
               9. Participant has received 2 or more live vaccinations (e.g., measles and yellow&#xD;
                  fever) within 30 days prior to receipt of BCG/placebo vaccine (Visit 2)&#xD;
&#xD;
              10. Participant has known or suspected hypersensitivity to BCG vaccine or related&#xD;
                  products&#xD;
&#xD;
              11. Participant has positive/borderline IGRA test at screening&#xD;
&#xD;
              12. Participant has positive/indeterminate HIV test at screening&#xD;
&#xD;
              13. Participant has a history of life-threatening adverse event following receipt of&#xD;
                  any immunization&#xD;
&#xD;
              14. Participant is known to have a behavioral, cognitive, or psychiatric disease that&#xD;
                  in the opinion of the investigator affects the ability of the participant to&#xD;
                  understand or cooperate with the requirements of the study protocol&#xD;
&#xD;
              15. Participant has other concurrent condition(s) that in the opinion of the&#xD;
                  investigator would jeopardize the safety or rights of a participant participating&#xD;
                  in the trial or would render the participant unable to comply with the protocol&#xD;
                  and/or compromise study objectives&#xD;
&#xD;
              16. Participant has had tuberculin skin testing performed within 1 month prior to&#xD;
                  Visit 1&#xD;
&#xD;
              17. Participant has received a COVID-19 vaccine within 7 days prior to BCG/placebo&#xD;
                  vaccine&#xD;
&#xD;
              18. Participant has had a probable exposure to TB (defined as to someone with&#xD;
                  suspected or confirmed pulmonary TB who is likely infectious) within 8-10 weeks&#xD;
                  of Visit 1&#xD;
&#xD;
              19. Participant has prior history of nontuberculous mycobacterial disease, not&#xD;
                  colonization only&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Naomi E. Aronson, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Uniformed Services University of the Health Sciences</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Merlin L. Robb, MD</last_name>
    <role>Study Director</role>
    <affiliation>Henry M. Jackson Foundation for the Advancement of Military Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kelly A. Hummer, RN, BSN</last_name>
    <phone>703-408-6273</phone>
    <email>kelly.hummer.ctr@usuhs.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marianne Spevak</last_name>
    <phone>240-694-2067</phone>
    <email>mspevak@hjf.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The UAB Alabama Vaccine Research Clinic</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kimberly Simmons, RN, BSN</last_name>
      <phone>205-975-2842</phone>
      <email>kpsimmons@uabmc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Savanna Spaulding, RN</last_name>
      <phone>(205) 975-8657</phone>
      <email>sspaulding@uabmc.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Paul Goepfert, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sonya Heath, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Heather Logan, CRNP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Savanna Spaulding, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kristen Spriggins, MPH</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>William Tingle, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurie Andrews, RN, MPH</last_name>
      <phone>203-785-3557</phone>
      <email>laurie.andrews@yale.edu</email>
    </contact>
    <contact_backup>
      <last_name>Anousheh Behnegar, MD</last_name>
      <phone>203) 737-6372</phone>
      <email>Anousheh.behnegar@yale.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Sheela Shenoi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Laurie Andrews, RN, MPH</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Anousheh Behnegar, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Grace Igiraneza, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Linda Ryall, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Terese Critch-Gilfillan, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hope Clinic of the Emory University Vaccine Center, Emory University</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tim Thurman</last_name>
      <phone>404-712-1479</phone>
      <email>timothy.b.thurman@emory.edu</email>
    </contact>
    <contact_backup>
      <last_name>Emily Osborne, RN</last_name>
      <phone>404) 712-1433</phone>
      <email>Emily.claire.osborne@emory.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Daniel Graciaa, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Srilatha Edupuganti, MD, MPH</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nadine Rouphael, MD, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Matthew Collins, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Cassie Grimsley-Ackerley, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Colleen Kelley, MD, MPH</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Paulina Rebolledo, MD, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Zanithia Wiley, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kristen Unterberger, PA-C</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mary Atha, MSN, ACNP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sharon Curate-Ingram, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Renata Dennis, RN, MPH</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Garett Michael</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ehsaywah Paw</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Brigham and Women's Hospital Center for Clinical Investigation</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sam Wong, BS</last_name>
      <phone>617-525-7654</phone>
      <email>swong1@bwh.harvard.edu</email>
    </contact>
    <contact_backup>
      <last_name>Haley Kondo</last_name>
      <phone>617) 525-7638</phone>
      <email>hekondo@bwh.harvard.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Edward Nardell, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>PENN Prevention Unit, University of Pennsylvania Division of Infectious Diseases</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chianti Wade-Bowers, RN</last_name>
      <phone>713-798-2147</phone>
      <email>Chianti.Wade-Bowers@bcm.edu</email>
    </contact>
    <contact_backup>
      <last_name>Chanei Henry</last_name>
      <phone>713-798-6957</phone>
      <email>ccoleman@bcm.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Hana El Sahly, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jennifer Whitaker, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Wendy Keitel, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Robert Atmar, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>C. Mary Healy, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Debbie Mathew, APRN, FNP-C</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Brandie Phillips, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Courtney Lymuel</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Janey John, APRN, FNP-C</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Dawn Turner, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kimberly Vu, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jessica Woods, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>JBR Clinical Research</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sam Gaufin</last_name>
      <phone>801-261-2000</phone>
      <phone_ext>2323</phone_ext>
      <email>s.gaufin@cenexel.com</email>
    </contact>
    <contact_backup>
      <last_name>Jenny Hunt</last_name>
      <phone>801) 261-2000</phone>
      <phone_ext>2313</phone_ext>
      <email>j.hunt@cenexel.com</email>
    </contact_backup>
    <investigator>
      <last_name>Todd M. Bertoch, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Stephen F. Richardson, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ryan M. Black, DO</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nancy M. Veit, NP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 17, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>April 27, 2023</last_update_submitted>
  <last_update_submitted_qc>April 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BCG Vaccine</keyword>
  <keyword>Tuberculosis vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Tuberculosis</mesh_term>
    <mesh_term>Latent Tuberculosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 22, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT04453293/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04453293
org study id: 2019-01
secondary id: BAA 170090
nct id: NCT04453293
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this research is to find out if a single dose of pre-travel vaccination with
      BCG can lessen tuberculosis (TB) infection by producing an immune response when given to
      adults traveling to countries with a high burden of TB. BCG will be compared with a placebo
      (an inactive vaccine). BCG (Japan) is used globally but is not approved for use in the United
      States, therefore it is considered experimental. Participants choosing to take part in this
      research study, will be randomly assigned (this is like a coin flip) to BCG or placebo. 2000
      eligible volunteers will be enrolled.
This study is a multi-center, prospective, randomized, placebo-controlled, participant and
      laboratory-blinded clinical trial to evaluate a single pre-travel vaccination with
      investigational freeze-dried glutamate BCG (Japan) to prevent Mycobacterium tuberculosis
      complex (Mtb) infection in healthy adult travelers, 18-65 years of age, exposed to persons
      with TB in high burden countries.

      The goals of this study are both public health and scientific. The public health goal of this
      study is to offer possible protection against TB to US workers traveling abroad to work in
      countries with a high burden of TB where there is a risk for multidrug resistant/extensively
      drug resistant TB exposure and where effective TB infection control interventions are
      infrequently fully implemented. A long-term scientific goal is to test the hypothesis that TB
      vaccination prevents primary TB infection as measured by peripheral blood TB interferon gamma
      release assay (IGRA) conversion at return from travel visit, as well as sustained conversion
      at approximately 4-6 months post-return from travel. Rates of IGRA conversion in
      BCG-vaccinated recipients as compared to placebo recipients will be evaluated. Additionally,
      this study will collect information regarding exposure to and infection with TB, assessing
      risk factors for TB infection during the participant's travel.

      This study will recruit two types of travelers: Type 1 travelers (Short-term travelers) that
      will be limited to health care workers traveling for 4 weeks, but less than 6 months and Type
      2 travelers (Long-term travelers) that will include those planning to reside in the country
      for 6 months or more (but ≤ 2.5 years duration), regardless of occupational group.

      High TB burden countries for this study are defined as countries identified in the World
      Health Organization (WHO) Global Tuberculosis Report 2020 to have a TB incidence of
      ≥70/100,000. Targeted participant population of travelers at-risk for high TB exposure will
      work specifically in one or more of the 74 highest ranked TB burden countries as recognized
      by the WHO 2020 report.

      Participants enrolled will be required to complete typically 4, but up to 6 study visits
      composed of: screening and eligibility assessments, vaccination with study vaccine (BCG or
      placebo), a subsequent post-vaccination follow-up assessment visit to identify potential
      adverse event occurrences, a post-travel follow-up visit to assess the risk factors for Mtb
      infection and assess the primary endpoint (IGRA conversion from negative to positive), and if
      applicable, an additional visit for those participants who are found to have a borderline
      IGRA result. For participants found to have post-travel IGRA conversion results, an
      additional visit will be requested for assessment of sustained TB IGRA conversion and
      reversion.

      Different evaluations, tests and/or procedures to be performed during study visits include:
      interviews relevant to their medical history and general well-being between study visits;
      physical examinations and vital signs; completion of a pre-travel questionnaire and
      post-travel questionnaires to collect information regarding exposure to TB and risk factors
      for infection, as well as any information regarding development of active TB disease, both
      pulmonary and/or extrapulmonary and evaluation for the presence and severity of self-reported
      symptomatic all-cause respiratory infection occurrences while traveling abroad; keeping a
      record to assess for occurrence of local reactions at the injection site and incidence of
      selected symptoms for the first 14 days post-vaccination; and blood draws (2 up to 4
      depending on what previous blood test results reveal).

      The study design is endpoint driven; designed to observe 56 total IGRA conversions.
      Therefore, enrollment into this study will be stopped if the target endpoint (56 IGRA
      conversions) are met earlier than expected.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, controlled trial of BCG (Tokyo 172) vaccine single dose given intradermally compared to placebo vaccine (diluent) given intradermally single dose
primary purpose: Prevention
masking: Single (Participant)
masking description: The participant and the laboratory (endpoint measurement) will be masked
measure: Change in TB IGRA blood test results from baseline pre-travel and post-travel return
time frame: At baseline, and 4-10 weeks post-travel return
description: Conversion change of TB IGRA from pre-travel baseline value of negative to positive post-travel, using FDA-approved breakpoints as a measure of Mycobacterium tuberculosis infection. Response will be assessed using technology of the T-SPOT.TB test method. Specifically, the test measures the number of spots from T cells sensitized to TB infection on a plate containing 4 different antigens: nil (negative control), 2 TB antigens (ESAT-6 and CFP-10, also called Panel A and Panel B), and phytohemagglutinin (positive control). Results are interpreted by subtracting the spot count in the negative (NIL) control from the spot count in Panels A and B:
Positive ≥ 8 spots
Negative ≤ 4 spots
Borderline 5, 6, or 7 spots
Invalid
measure: Number of Participants with sustained conversion and reversion in the TB IGRA converters
time frame: 4-6 months from return post-travel
description: Participants identified as having positive TB IGRA blood test results will undergo a TB IGRA re-test to determine sustained (positive result) conversion and reversion (defined as negative/borderline) using the T-SPOT.TB test method. The rate of conversion for each study group will be calculated as the number of conversions divided by person-months of travel
measure: Number of Participants with history of TB disease/symptoms while deployed
time frame: Through final IGRA testing, expected average time 4-10 weeks post-travel return
description: Participants with response of symptoms suggestive of TB disease (i.e., bloody cough, cough ≥ 2 weeks, chest pain, fever ≥ 2 weeks, night sweats, and unintentional weight loss), development of active TB disease (possible, probable, or definite) and TB treatment that may have occurred during travel to high burden TB country or up to the time of IGRA testing
measure: Identify potential risk factors for Mtb infection in the targeted study population collected on Post-Travel Questionnaire
time frame: Through final IGRA testing, expected average time 4-10 weeks post-travel return
description: Questionnaire responses from participants after travel will collect information regarding exposure to TB and risk factors for infection, as well as any information regarding risk reduction activities taken (i.e. personal protective measures) that may have occurred during travel to countries with high burden TB identified in the 2014 World Health Organization (WHO) TB report. Travelers will be asked if they had contact with anyone known to have TB disease or if they worked with populations at risk for HIV while abroad. They will also be asked about accommodations, daily routine, and if they used public transportation such as mini-buses and if so, how frequently. A final open-ended question e.g., "Do you have reason to believe you were exposed?" will be asked of all travelers
measure: Number of Participants with treatment-related adverse effects following intradermal administration of BCG vaccine
time frame: Baseline (pre-administration of vaccine), within 30 minutes of vaccination, 14-days post-vaccination, and 2 to 6 weeks post-vaccination (Visit 3)
description: Post-vaccination response to assess for occurrence of selected local injection site reactions (pain/tenderness, redness, ulceration, drainage, vesicle [blister], induration [swelling] and scarring), axillary/ cervical lymphadenopathy, and selected systemic symptoms (fever, headache, chills, dizziness, tiredness, nausea, gastrointestinal problems, rash, muscle and joint pain and general well-being) using the 2007 U.S. FDA guidance Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. For each reaction, the highest grade will be determined for each traveler. Participants will be provided with a memory aid card to record any occurrences of selected local reactions and systemic symptoms that may occur during the first 14-days post-vaccination
measure: Number of Participants with self-reported symptoms of all-cause respiratory infections acquired while traveling abroad
time frame: Through final IGRA testing, expected average time 4-10 weeks post-travel return
description: Questionnaire responses obtained from participants will assess self-reported symptomatic all-cause respiratory infection symptoms in five domains (nose, throat, chest, systemic, neurological) for presence, frequency of occurrence and severity, impact of acute symptoms on functional activities or productivity, and medical care encounters and treatment as a result of respiratory illness while traveling abroad.
arm group label: BCG vaccine
arm group type: Experimental
description: Freeze-dried Glutamate Bacillus Calmette-Guérin (BCG) (Tokyo 172) vaccine
arm group label: Placebo
arm group type: Placebo Comparator
description: Vaccine diluent [sodium glutamate]
intervention type: Biological
intervention name: BCG (Tokyo 172) vaccine
description: Freeze-Dried Glutamate Bacillus Calmette-Guérin BCG Vaccine (Japan BCG Laboratory), 0.1 mL given as single dose by intradermal injection over the outer lower aspect of the deltoid region
arm group label: BCG vaccine
intervention type: Drug
intervention name: Placebo
description: Placebo vaccine diluent, 0.1 mL given as single dose by intradermal injection over the outer lower aspect of the deltoid region
arm group label: Placebo
other name: sodium glutamate
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Naomi E. Aronson, MD
role: Study Chair
affiliation: Uniformed Services University of the Health Sciences
last name: Merlin L. Robb, MD
role: Study Director
affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine
last name: Kelly A. Hummer, RN, BSN
phone: 703-408-6273
email: kelly.hummer.ctr@usuhs.edu
last name: Marianne Spevak
phone: 240-694-2067
email: mspevak@hjf.org
facility: 
status: Recruiting
contact: 
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status: Recruiting
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status: Not yet recruiting
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status: Withdrawn
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status: Recruiting
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status: Recruiting
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country: United States
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Tuberculosis
mesh term: Latent Tuberculosis
sharing ipd: No
provided document: 