A Study to Evaluate the Efficacy, Safety and Immunogenicity of MTBVAC in Adolescents and Adults Living in a TB Endemic Region.

A Phase 2b, double-blind, randomized, placebo-controlled study to evaluate the efficacy, safety and immunogenicity of a candidate tuberculosis (TB) vaccine, MTBVAC, against TB disease in adolescents and adults aged 14-45 years, living in a TB endemic region.

Phase 2b, double-blind, randomized, placebo-controlled, safety and efficacy study in 5,500 healthy adults and adolescents. Participants will be enrolled based on IGRA status at baseline into an IGRA-positive cohort (n=4,300) or an IGRA-negative cohort (n=1,200). Most participants are likely to have received previous BCG vaccination in infancy. The investigational product is MTBVAC administered intradermally at 5x105 CFU. Participants meeting the enrolment criteria will be randomized, in a 1:1 ratio if baseline IGRA-positive or in a 3:1 ratio if baseline IGRA-negative, to receive a single dose of MTBVAC or placebo administered intradermally on Study Day 1. Participants will be followed up for efficacy following vaccination via regular visits or contacts to screen for possible TB. Participants will also be trained to recognize signs and symptoms consistent with pulmonary TB disease and to report them for clinical evaluation. Participants with clinical presumption of pulmonary TB will be assessed with confirmatory diagnostic testing using a Nucleic Acid Amplification Test (Xpert MTB/RIF Ultra assay) and microbiological culture in sputum sampled on 3 separate days within a 1 week period. Participants diagnosed with pulmonary TB will be referred for TB treatment according to local clinical practice. Only HIV-negative participants will be eligible for enrolment. Participants will be tested for HIV seroconversion at the end of each year of follow-up and at the presumptive TB visits. Participants who test positive for HIV will be referred for TB preventive treatment and antiretroviral treatment according to local clinical practice. A safety sub-cohort of approximately 660 participants (330 in each study arm) from the IGRA-positive cohort and 225 participants (150 MTBVAC and 75 placebo recipients) from the IGRA-negative cohort will be randomly selected for follow-up for solicited adverse events (AEs) and selected biochemistry and haematology. Additionally, an immunogenicity sub-cohort of approximately 90 participants (60 in the MTBVAC and 30 in the placebo arm) from the IGRA-positive cohort and 90 participants (60 in the MTBVAC and 30 in the placebo arm) from the IGRA-negative cohort will be randomly selected for specific immunogenicity assessments. All participants in the immunogenicity sub-cohort will participate in the safety sub-cohort. The sub-cohort randomization procedures will attempt to evenly distribute participants between adolescents (i.e., age 14 through 17) and adults (i.e., age 18 through 45) and among clinical research centres. The strategy for participant sub-cohort selection and randomization will be described in the Study Operations Manual (SOM) and Statistical Analysis Plan (SAP).