MTBVAC at four dose levels: 5 x 10\^3 CFU, 5 x 10\^4 CFU, 5 x 10\^5 CFU, and 5 x 10\^6 CFU. The active control is BCG (5 x 10\^5 CFU). Participants will receive a single dose of MTBVAC or BCG revaccination administered intradermally on Study Day 0.
This is a Phase 1b/2a, double-blind, randomized, BCG-controlled, dose-escalation safety and immunogenicity study in 144 healthy adults with and without LTBI. All participants will have received previous BCG vaccination in infancy. The investigational product is MTBVAC at four dose levels: 5 x 10\^3 CFU, 5 x 10\^4 CFU, 5 x 10\^5 CFU, and 5 x 10\^6 CFU. The active control is BCG (5 x 10\^5 CFU). Participants meeting the inclusion/exclusion criteria will be randomized within a study cohort to receive a single dose of MTBVAC or BCG revaccination administered intradermally on Study Day 0. The study will be conducted at one site in South Africa. Participants will be enrolled into one of eight cohorts and followed for safety and immunogenicity endpoints through Study Day 365. The estimated time to complete enrolment is approximately 12 months. Cohorts 1-8 will include 72 QFT-negative (Cohorts 1-4) and 72 QFT-positive (Cohorts 5-8) participants. Participants will be randomized within each cohort, to receive either MTBVAC (N=96) or BCG (N=48). The cohorts will be enrolled as described in the protocol, as long as no pausing/stopping rules are triggered
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
144
SATVI: Worcester
Worcester, South Africa
Safety and reactogenicity of MTBVAC at escalating dose levels compared to BCG vaccine by assessing number of participants with AEs and SAEs
Collection of systemic solicited and unsolicited adverse events; solicited and unsolicited injection site reactions; and serious adverse reactions.
Time frame: Study Days 0 to Day 365
Difference in T cell response between MTBVAC dose levels across all post-immunization time points measured by percentage of MTBVAC-specific CD4 and CD8 T cells that produce any or a combination of relevant cytokines in ICS assay
12 hour whole blood (WB) intracellular cytokine staining (ICS) assay
Time frame: Study Days 0, 28, 56, 182, and 365
Qualitative and quantitative results from QuantiFERON® TB (QFT) test summarized using participant count (percentage) summaries conversion and reversion rates in participants receiving escalating dose levels of MTBVAC
QFT Gold Plus assay
Time frame: Screening and Study Day 365 (all cohorts); and Study Days 28, 56, 84, and 182 (Cohorts 1-4)
Qualitative and quantitative results from QFT test using percentage conversion and reversion rates of participants receiving escalating dose levels of MTBVAC compared to BCG dose levels of MTBVAC in comparison to BCG measured by QFT Gold Plus assay
QFT Gold Plus assay
Time frame: Screening and Study Day 365 (all cohorts); and Study Days 28, 56, 84, and 182 (Cohorts 1-4)
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