Immunization With BCG Vaccine to Prevent Tuberculosis Infection

NCT04453293 | Terminated Phase 3 DMC FDA Drug

• 2 other identifiers: 2019-01BAA 170090
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 7

Brief 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 or moderate 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.

Conditions

Tuberculosis Infection

Keywords

BCG Vaccine; Tuberculosis vaccine

Outcome Measures

Primary Outcomes (1)

• Change in TB IGRA blood test results from baseline pre-travel and post-travel return

  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 (this includes values less than zero) * Borderline 5, 6, or 7 spots * Invalid

  At baseline, and 8-10 weeks post-travel return

Secondary Outcomes (5)

• Number of Participants with sustained conversion and reversion in the TB IGRA converters

  4-6 months from return post-travel

• Number of Participants with history of TB disease/symptoms while deployed

  Through final IGRA testing, expected average time 8-10 weeks post-travel return

• Identify potential risk factors for Mtb infection in the targeted study population collected on Post-Travel Questionnaire

  Through final IGRA testing, expected average time 8-10 weeks post-travel return

• Number of Participants with treatment-related adverse effects following intradermal administration of BCG vaccine

  Baseline (pre-administration of vaccine), within 30 minutes of vaccination, 14-days post-vaccination, and 2 to 6 weeks post-vaccination (Visit 3)

• Number of Participants with self-reported symptoms of all-cause respiratory infections acquired while traveling abroad

  Through final IGRA testing, expected average time 8-10 weeks post-travel return

Study Arms (2)

BCG vaccine

EXPERIMENTAL

Freeze-dried Glutamate Bacillus Calmette-Guérin (BCG) (Tokyo 172) vaccine

Biological: BCG (Tokyo 172) vaccine

Placebo

PLACEBO COMPARATOR

Vaccine diluent \[sodium glutamate\]

Drug: Placebo

Interventions

BCG (Tokyo 172) vaccine BIOLOGICAL

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

BCG vaccine

Placebo DRUG

Placebo vaccine diluent, 0.1 mL given as single dose by intradermal injection over the outer lower aspect of the deltoid region

Also known as: sodium glutamate

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants will be eligible for study participation if they meet all of the following criteria:
• 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
• Participant is male or female, age ≥ 18 years and ≤ 65 years at time of consent
• Participant is in good general health, confirmed by medical history, laboratory screening, and physical examination
• Participant has no known history of Mtb infection
• Participant has no prior history of BCG vaccination, or previous receipt of an investigational Mtb vaccine
• Participant is assessed to be at risk for TB exposure (particularly drug resistant TB) during planned travel and has planned to work in high or moderate TB burden countries for a duration of a minimum of 10 days and not greater than 6 months for HCW
• Participant presents at least 4 weeks prior to travel departure
• Participant is willing to forego any periodic tuberculin skin test screening procedures for 6 months after receiving BCG/placebo vaccine
• Participant is willing to wait after receiving a COVID-19 vaccine for 7 days before receiving BCG/placebo vaccine
• Participant is willing to complete all study visits as required by the protocol and is reachable by telephone or email during the study
• Participant agrees to medical record access for purposes of relevant medical history collection
• For Females of Childbearing Potential Only:
• Participant has a negative urine pregnancy test prior to starting study treatment
• Participant is willing to use effective contraception for at least 30 days before and 6 weeks after BCG/placebo vaccination

You may not qualify if:

• Participants will be ineligible for study participation if they meet any of the following criteria:
• Participant has known positive tuberculin skin test (\>10 mm) or positive IGRA
• Participant has medical condition for which BCG vaccination is contraindicated (e.g., HIV or other immunocompromised conditions)
• Participant is currently receiving (within last 30 days) immune-compromising treatments, such as TNF-α blockade
• Participant has history of chronic (≥ 30 days) oral steroid use or intravenous (IV) steroids within the last 90 days
• Participant has received radiation therapy or chemotherapy within the last 180 days
• Participant has received BCG treatment for bladder cancer
• 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
• Participant is unwilling to complete all required study elements (e.g., HIV testing)
• 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)
• Participant has known or suspected hypersensitivity to BCG vaccine or related products
• Participant has positive/borderline IGRA test at screening
• Participant has positive/indeterminate HIV test at screening unless has received prior HIV vaccine
• Participant has a history of life-threatening adverse event following receipt of any immunization
• 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

Sponsors & Collaborators

• Henry M. Jackson Foundation for the Advancement of Military Medicine: lead
• United States Department of Defense: collaborator
• Uniformed Services University of the Health Sciences: collaborator

Study Sites (7)

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

MedStar Washington Hospital Center/MedStar Health Research Institute

Washington D.C., District of Columbia, 20010, United States

Location

Hope Clinic of the Emory University Vaccine Center, Emory University

Decatur, Georgia, 30030, United States

Location

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

Baltimore, Maryland, 21205, United States

Location

The Brigham and Women's Hospital Center for Clinical Investigation

Boston, Massachusetts, 02115, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84108, United States

Location

MeSH Terms

Conditions

Latent Tuberculosis

Interventions

Vaccines; Sodium Glutamate

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures; Glutamic Acid; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Naomi E. Aronson, MD

  Uniformed Services University of the Health Sciences

  STUDY CHAIR

• Merlin L. Robb, MD

  Henry M. Jackson Foundation for the Advancement of Military Medicine

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The participant and the laboratory (endpoint measurement) will be masked
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, controlled trial of BCG (Tokyo 172) vaccine single dose given intradermally compared to placebo vaccine (diluent) given intradermally single dose

Study Record Dates

• First Submitted: June 17, 2020
• First Posted: July 1, 2020
• Study Start: December 1, 2021
• Primary Completion: January 16, 2026
• Study Completion: January 16, 2026
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)