A nonrandomized, open-label trial will be conducted with a total of 64 healthy male and non-pregnant females, ages 18-45 years. Participants in Group A will enroll 32 participants to receive 2x10\^6 colony- forming units CFU TICE(R) BCG vaccination on Day 1 and 4x10\^6 CFU challenge on Day 181. Once enrollment has been completed in Group A, participants in Group B will be enrolled sequentially to receive 4x10\^6 CFU challenge. The primary objectives are to evaluate the safety of intradermal (ID) TICE(R) BCG for use as a human challenge model for Mycobacterium tuberculosis (Mtb) infection and to examine BCG shedding from challenge sites in participants who had received ID vaccination with TICE(R) BCG or were not vaccinated six months prior.
A nonrandomized, open-label trial will be conducted with a total of 64 healthy male and non-pregnant females, ages 18-45 years. Participants in Group A will enroll 32 participants to receive 2x10\^6 colony- forming units (CFU) TICE(R) BCG vaccination on Day 1 and 4x10\^6 CFU challenge on Day 181. Once enrollment has been completed in Group A, participants in Group B will be enrolled sequentially to receive 4x10\^6 CFU challenge. The primary objectives are to evaluate the safety of intradermal (ID) TICE(R) BCG for use as a human challenge model for Mycobacterium tuberculosis (Mtb) infection and to examine BCG shedding from challenge sites in participants who had received ID vaccination with TICE(R) BCG or were not vaccinated six months prior. The secondary objectives are to 1) evaluate the safety of ID TICE(R) BCG after vaccination, 2) examine BCG shedding by MGIT assay from challenge sites in participants who had received ID vaccination with TICE(R) BCG or were not vaccinated six months prior, 3) examine BCG shedding from challenge sites in participants that had received ID vaccination with TICE(R) BCG or were not vaccinated six months prior using additional assays, 4) characterize the T cell responses after BCG challenge in participants that received ID vaccination with TICE(R) BCG or not vaccinated six months prior and 5) determine whether IFN-gamma correlates with levels of BCG shedding.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
BCG TICE strain is an attenuated, live culture preparation of the BCG strain of Mycobacterium bovis.
0.9% Sodium Chloride Injection
A sterile, nonpyrogenic preparation of water for injection which contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection
Distribution of the area under the curve (AUC) for repeated measures of shedding over time from mycobacteria growth indicator tube (MGIT) BACTEC assays after intradermal (ID) TICE (R) Bacille Calmette-Guerin (BCG) challenge
Time frame: Day 185 through Day 237
Serious adverse events (SAE) and/ or Medically Attended Adverse Events (MAAEs) related to intradermal (ID) TICE (R) Bacille Calmette-Guerin (BCG) challenge
Time frame: Day 181 through Day 361
The number of participants experiencing Grade 3 (severe) or higher clinical safety laboratory adverse events (AEs) following intradermal (ID) TICE(R) Bacille Calmette-Guerin (BCG) challenge
Time frame: Day 181 through Day 188
The number of participants experiencing Grade 3 (severe) or higher solicited injection site reactions following intradermal (ID) TICE(R) Bacille Calmette-Guerin (BCG) challenge
Time frame: Day 181 through Day 236
The number of participants experiencing Grade 3 (severe) or higher solicited systemic reactions following intradermal (ID) TICE(R) Bacille Calmette-Guerin (BCG) challenge
Time frame: Day 181 through Day 195
The number of participants reporting Grade 3 (severe) or higher adverse events (AEs) related to intradermal (ID) TICE (R) Bacille Calmette-Guerin (BCG) challenge
Time frame: Day 181 through Day 237
Analyze the adaptive immune responses associated with immunogenicity and reactogenicity
Measured using IFN-gamma ELISPOT assay
Time frame: Day 181 through Day 279
Comparison of area under the curve (AUC) for repeated measures of shedding over time from MGIT BACTEC assays intradermal (ID) TICE (R) Bacille Calmette-Guerin (BCG) challenge between unvaccinated and vaccinated groups.
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Time frame: Day 4 through Day 57
Distribution of the area under the curve (AUC) for repeated measures of shedding over time from colony-forming units (CFU) assays after intradermal (ID) TICE (R) Bacille Calmette-Guerin (BCG) challenge.
Time frame: Days 4 through Day 57
Distribution of the area under the curve (AUC) for repeated measures of shedding over time from quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays after intradermal (ID) TICE (R) Bacille Calmette-Guerin (BCG) challenge.
Time frame: Days 4 through Day 57
Medically Attended Adverse Events (MAAEs) and Serious adverse events related to intradermal (ID) TICE (R) Bacille Calmette-Guerin (BCG) administration after vaccination
Time frame: Day 1 through Day 181
Test correlations between interferon gamma (IFN-gamma) ELISPOT responses and Bacille Calmette-Guerin (BCG) shedding
Time frame: Day 181 through Day 279
The number of participants experiencing Grade 3 (severe) injection site reactions following intradermal (ID) TICE (R) Bacille Calmette-Guerin (BCG) vaccination.
Time frame: Day 1 through Day 30
The number of participants experiencing Grade 3 (severe) or higher clinical safety laboratory adverse events (AEs) following intradermal (ID) TICE (R) Bacille Calmette-Guerin (BCG) vaccination.
Time frame: Day 1 through Day 181
The number of participants experiencing Grade 3 (severe) or higher solicited systemic reactions following intradermal (ID) TICE (R) Bacille Calmette-Guerin (BCG) vaccination.
Time frame: Day 1 through Day 30
The number of participants reporting Grade 3 (severe) or higher adverse events (AEs) related to intradermal (ID) TICE (R) Bacille Calmette-Guerin (BCG) vaccination
Time frame: Day 1 through Day 57