Immunization With BCG Vaccine to Prevent Tuberculosis Infection

Overview

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.

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 or moderate 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 health care workers (public health workers or students in training status) traveling to countries with a high or moderate burden of TB where there is a risk for multidrug resistant/extensively drug resistant (MDR/XDR) for a minimum of 10 days up through 6 months, with planned exposure to the local population such as patient care activities. Performance sites will not enroll anyone traveling for greater than 6 months or longer. High or moderate 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 ≥20/100,000. Targeted participant population of travelers at-risk for high TB exposure will work specifically in one or more of the 131 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.