Immunization With BCG Vaccine to Prevent Tuberculosis Infection

Last updated: May 19, 2025
Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
Overall Status: Active - Recruiting

Phase

3

Condition

Hiv

Lung Disease

Treatment

Placebo

BCG (Tokyo 172) vaccine

Clinical Study ID

NCT04453293
2019-01
BAA 170090
  • Ages 18-65
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Participants will be eligible for study participation if they meet all of thefollowing criteria:

  1. Participant is willing to participate in the study as evidenced by providingvoluntary written informed consent and Health Insurance Portability andAccountability Act (HIPAA) authorization prior to conducting any trial relatedprocedures

  2. Participant is male or female, age ≥ 18 years and ≤ 65 years at time of consent

  3. Participant is in good general health, confirmed by medical history, laboratoryscreening, and physical examination

  4. Participant has no known history of Mtb infection

  5. Participant has no prior history of BCG vaccination, or previous receipt of aninvestigational Mtb vaccine

  6. Participant is assessed to be at risk for TB exposure (particularly drugresistant TB) during planned travel and has planned to work in high TB burdencountries for a duration of >4 weeks and <6 months for HCW, or ≥6 months and ≤2.5 years if long term traveler and/or/HCW

  7. Participant presents at least 4 weeks prior to travel departure

  8. Participant is willing to forego any periodic tuberculin skin test screeningprocedures for 6 months after receiving BCG/placebo vaccine

  9. Participant is willing to wait after receiving a COVID-19 vaccine for 7 daysbefore receiving BCG/placebo vaccine

  10. Participant is willing to complete all study visits as required by the protocoland is reachable by telephone or email during the study

  11. Participant agrees to medical record access for purposes of relevant medicalhistory collectionFor Females of Childbearing Potential Only:

  12. Participant has a negative urine pregnancy test prior to starting studytreatment

  13. Participant is willing to use effective contraception for at least 30 daysbefore and 6 weeks after BCG/placebo vaccination

  14. Lactating female that is willing to refrain from breast-feeding for 6 weekspost-vaccination

Exclusion

Exclusion Criteria:

  • Participants will be ineligible for study participation if they meet any of thefollowing criteria:

  1. Participant has known positive tuberculin skin test (>10 mm) or positive IGRA

  2. Participant has medical condition for which BCG vaccination is contraindicated (e.g., HIV or other immunocompromised conditions)

  3. Participant is currently receiving (within last 30 days) immune-compromisingtreatments, such as TNF-α blockade

  4. Participant has history of chronic (≥ 30 days) oral steroid use or intravenous (IV) steroids within the last 90 days

  5. Participant has received radiation therapy or chemotherapy within the last 180days

  6. Participant has received BCG treatment for bladder cancer

  7. Participant is female and is pregnant (as defined by positive urine βHCG test)or intends to become pregnant in next 3 months, or is breast-feeding atscreening or vaccination visit

  8. Participant is unwilling to complete all required study elements (e.g., HIVtesting)

  9. Participant has received 2 or more live vaccinations (e.g., measles and yellowfever) within 30 days prior to receipt of BCG/placebo vaccine (Visit 2)

  10. Participant has known or suspected hypersensitivity to BCG vaccine or relatedproducts

  11. Participant has positive/borderline IGRA test at screening

  12. Participant has positive/indeterminate HIV test at screening unless hasreceived prior HIV vaccine

  13. Participant has a history of life-threatening adverse event following receiptof any immunization

  14. Participant is known to have a behavioral, cognitive, or psychiatric diseasethat in the opinion of the investigator affects the ability of the participantto understand or cooperate with the requirements of the study protocol

  15. Participant has other concurrent condition(s) that in the opinion of theinvestigator would jeopardize the safety or rights of a participantparticipating in the trial or would render the participant unable to complywith the protocol and/or compromise study objectives

  16. Participant has had tuberculin skin testing performed within 1 month prior toVisit 1

  17. Participant has received a COVID-19 vaccine within 7 days prior to BCG/placebovaccine

  18. Participant has had a probable exposure to TB (defined as to someone withsuspected or confirmed pulmonary TB who is likely infectious) within 8-10 weeksof Visit 1

  19. Participant has prior history of nontuberculous mycobacterial disease, notcolonization only

Study Design

Total Participants: 2000
Treatment Group(s): 2
Primary Treatment: Placebo
Phase: 3
Study Start date:
December 01, 2021
Estimated Completion Date:
September 30, 2027

Study Description

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 82 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.

Connect with a study center

  • The UAB Alabama Vaccine Research Clinic

    Birmingham, Alabama 35294
    United States

    Site Not Available

  • Yale University

    New Haven, Connecticut 06510
    United States

    Active - Recruiting

  • Yale University School of Medicine

    New Haven, Connecticut 06510
    United States

    Site Not Available

  • MedStar Washington Hospital Center/MedStar Health Research Institute

    Washington, District of Columbia 20010
    United States

    Active - Recruiting

  • Hope Clinic of the Emory University Vaccine Center, Emory University

    Decatur, Georgia 30030
    United States

    Terminated

  • Johns Hopkins Bloomberg School of Public Health, Department of International Health, Center for Immunization Research

    Baltimore, Maryland 21205
    United States

    Active - Recruiting

  • The Brigham and Women's Hospital Center for Clinical Investigation

    Boston, Massachusetts 02115
    United States

    Site Not Available

  • PENN Prevention Unit, University of Pennsylvania Division of Infectious Diseases

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

  • Vanderbilt Clinical Research Center (Vanderbilt University Medical Center)

    Nashville, Tennessee 37232
    United States

    Site Not Available

  • Baylor College of Medicine

    Houston, Texas 77030
    United States

    Site Not Available

  • JBR Clinical Research

    Salt Lake City, Utah 84107
    United States

    Active - Recruiting

  • University of Utah School of Medicine

    Salt Lake City, Utah 84108
    United States

    Site Not Available

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