Vaccination with BCG to prevent tuberculosis for travelers

A Proof-of Concept, Randomized, Controlled Study of Tuberculosis Immunization With BCG to Prevent Infection in Healthy Adults (TIPI Trial)

This study is testing if a single BCG vaccine can help healthy adults aged 18-65 avoid getting tuberculosis while traveling to countries where TB is common.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 2000 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 7 sites (New Haven, Connecticut and 6 other locations)
• Trial ID: NCT04453293 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of a single pre-travel vaccination with BCG vaccine in preventing tuberculosis (TB) infection among healthy adults aged 18-65 traveling to high TB burden countries. Participants will be randomly assigned to receive either the BCG vaccine or a placebo, and the study aims to measure the immune response and rates of TB infection through blood tests. The trial will enroll 2000 volunteers and is designed to assess both public health benefits and scientific hypotheses regarding TB vaccination. The study will also gather data on participants' exposure to TB during their travels.

Who should consider this trial

Good fit: Ideal candidates are healthy adults aged 18-65 who are planning to work in high TB burden countries for more than 4 weeks.

Not a fit: Patients with a known history of TB infection or prior BCG vaccination may not benefit from this study.

Why it matters

Potential benefit: If successful, this vaccination could significantly reduce the risk of tuberculosis infection for travelers to high-burden areas.

How similar studies have performed: Other studies have shown promise in using BCG vaccination for TB prevention, but this specific approach is considered experimental in the U.S.

Eligibility criteria

Inclusion Criteria:

* Participants will be eligible for study participation if they meet all of the following criteria:

  1. Participant is willing to participate in the study as evidenced by providing voluntary written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization prior to conducting any trial related procedures
  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, laboratory screening, 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 an investigational Mtb vaccine
  6. Participant is assessed to be at risk for TB exposure (particularly drug resistant TB) during planned travel and has planned to work in high TB burden countries 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 screening procedures for 6 months after receiving BCG/placebo vaccine
  9. Participant is willing to wait after receiving a COVID-19 vaccine for 7 days before receiving BCG/placebo vaccine
  10. Participant is willing to complete all study visits as required by the protocol and is reachable by telephone or email during the study
  11. Participant agrees to medical record access for purposes of relevant medical history collection

      For Females of Childbearing Potential Only:
  12. Participant has a negative urine pregnancy test prior to starting study treatment
  13. Participant is willing to use effective contraception for at least 30 days before and 6 weeks after BCG/placebo vaccination
  14. Lactating female that is willing to refrain from breast-feeding for 6 weeks post-vaccination

Exclusion Criteria:

* Participants will be ineligible for study participation if they meet any of the following 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-compromising treatments, 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 180 days
  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 at screening or vaccination visit
  8. Participant is unwilling to complete all required study elements (e.g., HIV testing)
  9. Participant has received 2 or more live vaccinations (e.g., measles and yellow fever) within 30 days prior to receipt of BCG/placebo vaccine (Visit 2)
  10. Participant has known or suspected hypersensitivity to BCG vaccine or related products
  11. Participant has positive/borderline IGRA test at screening
  12. Participant has positive/indeterminate HIV test at screening unless has received prior HIV vaccine
  13. Participant has a history of life-threatening adverse event following receipt of any immunization
  14. Participant is known to have a behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand or cooperate with the requirements of the study protocol
  15. Participant has other concurrent condition(s) that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial or would render the participant unable to comply with the protocol and/or compromise study objectives
  16. Participant has had tuberculin skin testing performed within 1 month prior to Visit 1
  17. Participant has received a COVID-19 vaccine within 7 days prior to BCG/placebo vaccine
  18. Participant has had a probable exposure to TB (defined as to someone with suspected or confirmed pulmonary TB who is likely infectious) within 8-10 weeks of Visit 1
  19. Participant has prior history of nontuberculous mycobacterial disease, not colonization only

Where this trial is running

New Haven, Connecticut and 6 other locations

• Yale University School of Medicine — New Haven, Connecticut, United States (Active_not_recruiting)
• MedStar Washington Hospital Center/MedStar Health Research Institute — Washington, District of Columbia, United States (Recruiting)
• Hope Clinic of the Emory University Vaccine Center, Emory University — Decatur, Georgia, United States (Terminated)
• Johns Hopkins Bloomberg School of Public Health, Department of International Health, Center for Immunization Research — Baltimore, Maryland, United States (Recruiting)
• The Brigham and Women's Hospital Center for Clinical Investigation — Boston, Massachusetts, United States (Active_not_recruiting)
• Baylor College of Medicine — Houston, Texas, United States (Active_not_recruiting)
• University of Utah School of Medicine — Salt Lake City, Utah, United States (Active_not_recruiting)

Study contacts

• Study coordinator: Kelly A. Hummer, RN, BSN

Conditions Tuberculosis Infection; BCG Vaccine; Tuberculosis vaccine