BCG Vaccination Delivered Intradermally, Orally and by Combined Routes
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will assess the safety of a Bacillus Calmette-Guérin (BCG) vaccine against
      tuberculosis (TB) and will evaluate if giving the vaccine by mouth, injection, or by both
      methods produces greater results. BCG vaccine and/or placebo (substance containing no
      medication) will be given by mouth and/or by injection into the skin. This study, conducted
      at Saint Louis University, will enroll 60 (up to 80) healthy volunteers, 18-40 years old, who
      are negative for a TB test (QuantiFERON®-Gold) and human immunodeficiency virus (HIV). Study
      procedures will include a physical exam; review of TB exposure history and medical history;
      collection of multiple samples of blood, urine, stool, tears, and nose fluid; and skin and
      blood tests for TB. Volunteers may participate for about 24 months.
    

Detailed description: 
      Vaccination with Bacillus Calmette-Guérin (BCG) is used as part of tuberculosis (TB) control
      strategies in most of the world outside of the United States and constitutes the most widely
      implemented vaccination strategy worldwide. However, despite widespread use of BCG, TB
      remains a leading infectious cause of death worldwide and it is estimated that one-third of
      the world's population is chronically and asymptomatically (latently) infected with
      Mycobacterium tuberculosis (Mtb), the causative agent of TB. This is a phase I,
      single-center, randomized, vaccine trial including six double-blind, placebo-controlled
      groups and one open-label group. Approximately 68 (up to 80) healthy male and female subjects
      18-40 years old, inclusive, who are negative for QuantiFERON®-TB Gold and human
      immunodeficiency virus will be enrolled. The expected total duration of the volunteer
      enrollment, vaccination, and follow-up (volunteer participation) for this study is 30 months.
      All volunteers are expected to be enrolled over a period of 9 months and on study for 24
      months. Detailed immune studies with frozen samples will be expected to continue after
      collection of all samples and after the protocol has been completed. Eligibility will be
      determined by volunteer's health at prescreening and eligible subjects will give study
      specific main study informed consent for enrollment in the study. Subjects randomized to
      Groups A-F will receive, at Day 0 and 1 year later, BCG intradermally, orally, or by both
      routes. PBS (PO) and Sauton medium (injectable) placebo will be used to blind the study.
      Subjects randomized to Group G will receive BCG intradermally at Day 0 only. The primary
      study objectives are the assessment of the safety of combined and individual intradermal (ID)
      and oral (PO) vaccination with Statens Serum Institut (SSI) BCG in healthy, immunologically
      naïve volunteers; comparisons of mycobacteria-specific interferon-gamma responses and mucosal
      immunoglobulin-A induced by SSI BCG vaccination given intradermally, orally and by both
      routes combined; and comparison of safety and immunogenicity of Danish and Connaught BCG
      given intradermally. The secondary study objectives are the assessment of purified protein
      derivative skin test responses as an indication of cutaneous T cell trafficking after
      vaccination with SSI BCG; and quantitation of BCG replication in Sanofi Pasteur ID BCG
      ulcerative lesions after ID BCG vaccination. The exploratory study objectives are comparisons
      of intracellular killing activity induced by SSI BCG vaccination given intradermally, orally,
      and by both routes combined; and characterization of mycobacteria-specific T cells induced
      intradermally, orally, or both routes by vaccination with SSI BCG using dendritic cells as
      antigen-presenting cells and stored peripheral blood mononuclear cells as a source for
      matched T cells collected before and after vaccination. Parent protocol to sub-study 12-0110
      and 10-0026.
    

Intervention name(s): BCG strain Connaught; BCG strain Danish; BCG strain Danish; Placebo; Placebo
Intervention type(s): Biological; Biological; Biological; Other; Other
Intervention description(s): Connaught strain Bacillus Calmette-Guerin (BCG), 8-32 x 10^5 CFU vaccine for intradermal administration.; Bacillus Calmette-Guerin (BCG) strain Danish from the Statens Serum Institute (SSI BCG). 1.2 X 10^8 colony-forming units (CFU) oral (PO) in 60 mililiters phosphate buffered saline (PBS).; Bacillus Calmette-Guerin (BCG) strain Danish from the Statens Serum Institute (SSI BCG). 2-8 X 10^5 colony-forming units (CFU) intradermal in 100 microliters diluent.; 0.1 mL of sterile Sauton medium for intradermal administration.; 60 mL of sterile phosphate buffered saline (PBS) for oral administration.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Bacillus Calmette-Guérin; parent protocol; tuberculosis