MTBVAC Study in Adults With and Without Latent Tuberculosis Infection in South Africa

Phase 1

Completed

Brief Summary: 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.

Detailed Description: 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

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Cohort 2: MTBVAC 5 x 10^4 CFU	MTBVAC	QFT Negative, 1 dose on Day 0
Cohort 8: MTBVAC 5 x 10^6 CFU	MTBVAC	QFT Positive, 1 dose on Day 0
BCG 5 x 10^5 CFU	BCG	Both QFT positive and negative, 1 dose on Day 0
Cohort 5: MTBVAC 5 x 10^3 CFU	MTBVAC	QFT Positive, 1 dose on Day 0
Cohort 1: MTBVAC 5 x 10^3 CFU	MTBVAC	Quantiferon (QFT) negative, 1 dose on Day 0
Cohort 3: MTBVAC 5 x 10^5 CFU	MTBVAC	QFT Negative, 1 dose on Day 0
Cohort 7: MTBVAC 5 x 10^5 CFU	MTBVAC	QFT Positive, 1 dose on Day 0
Cohort 4: MTBVAC 5 x 10^6 CFU	MTBVAC	QFT Negative, 1 dose on Day 0
Cohort 6: MTBVAC 5 x 10^4 CFU	MTBVAC	QFT Positive, 1 dose on Day 0

Primary Outcome Measures

Name	Time	Method
Safety and reactogenicity of MTBVAC at escalating dose levels compared to BCG vaccine by assessing number of participants with AEs and SAEs	Study Days 0 to Day 365	Collection of systemic solicited and unsolicited adverse events; solicited and unsolicited injection site reactions; and serious adverse reactions.

Secondary Outcome Measures

Name	Time	Method
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	Study Days 0, 28, 56, 182, and 365	12 hour whole blood (WB) intracellular cytokine staining (ICS) assay
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	Screening and Study Day 365 (all cohorts); and Study Days 28, 56, 84, and 182 (Cohorts 1-4)	QFT Gold Plus assay
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	Screening and Study Day 365 (all cohorts); and Study Days 28, 56, 84, and 182 (Cohorts 1-4)	QFT Gold Plus assay

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