Tuberculosis (TB) is a major cause of death worldwide. Because TB is very harmful and there are difficulties in treating and preventing it, there is a strong need for a vaccine to protect people from getting sick with TB and to help stop the spread of the disease. MTBVAC is a weakened form of human tuberculosis bacteria. It has the same genes as the bacteria but with two genes removed to stop it from causing TB disease. A company called BIOFABRI, S.L.U. in Spain made and tested MTBVAC as a freeze-dried vaccine according to strict guidelines to comply with Good Manufacturing Practices (GMP).

This study aims to check how effective this vaccine is in preventing TB disease in the lungs in adolescents and adults living in areas where TB is common and who test positive M.tb infection TB and who are HIV negative. The study will also do further checks on whether it is safe to use the vaccine in humans and how their immune system will respond to the vaccine.

In this study, neither the participants nor the researchers will know who is receiving the actual treatment or an inactive treatment (placebo). It will include 4,300 healthy adults and adolescents who have tested positive for M.tb infection  with a specific immune response blood test known as Interferon-Gamma Release Assay (IGRA). People from various locations in South and Eastern Africa will be invited to take part, and those who meet the requirements will be randomly assigned to receive either a single dose of the vaccine called MTBVAC or a placebo on the first day of the study. Before getting the vaccine, participants will undergo tests up to 30 days in advance, and they will be monitored for a minimum of 24 months and a maximum of 36 months after receiving the vaccine.

MTBVAC has been found to be safe and effective in preventing pulmonary tuberculosis in both adult and newborn animals. It has been shown to be as safe as BCG but more effective in generating an immune response. This research supports the need for human trials to further evaluate its potential in preventing tuberculosis in areas where the disease is common. The study aims to provide initial evidence of MTBVAC's effectiveness in protecting against pulmonary tuberculosis among adolescent and adult humans.

Worldwide, tuberculosis (TB) is one of the leading causes of death from a single infectious agent. Given the substantial morbidity and mortality associated with TB, challenges associated with TB treatment and limited options for prevention, a vaccine is urgently needed, to protect against the disease, including the progression from lMycobacterium Tuberculosis (M.tb) infection to active TB, and to accelerate the end of the TB epidemic.

MTBVAC is a live rationally attenuated derivative of a human M.tb isolate. It contains all the genes present in M.tb strains and two independent stable deletions in the virulence genes phoP and fadD26. The Spanish vaccine manufacturer BIOFABRI, S.L.U. has produced and characterized the live MTBVAC as a freeze-dried preparation in compliance with Good Manufacturing Practices following the European Pharmacopoeia monograph and the WHO Recommendations to Assure the Quality, Safety and Efficacy of BCG Vaccines.

MTBVAC has shown adequate attenuation and safety profile comparable to BCG, with superior immunogenicity and efficacy against pulmonary forms of TB in adult and newborn animal models supporting evaluation in human clinical trials. The study will serve as a “proof-of-concept" investigation, intended to obtain, for the first time, evidence of MTBVAC efficacy in preventing pulmonary TB disease in adolescents and adults living in TB endemic areas. Demonstration of safety and efficacy in this study will provide the basis for progression to a phase 3 licensure/registration study thus closing the gap towards new vaccine arsenals against tuberculosis disease among adolescents and adults.

The primary goal of this phase 2b study is to assess the efficacy of MTBVAC in preventing pulmonary TB disease in Interferon-Gamma Release Assay (IGRA) positive, Human Immunodeficiency Virus (HIV)-negative adolescents and adults living in areas endemic for TB. The study also will assess MTBVAC safety and immunogenicity.

The study is a double-blind, randomized, placebo-controlled, safety and efficacy study in 4,300 healthy adults with a positive IGRA test result. Participants will be enrolled by multiple Clinical Research Centres (CRCs) globally, and those meeting the enrolment criteria will be randomized in a 1:1 ratio to receive a single dose of MTBVAC or placebo administered intradermally on Study Day 1.

Participants will then be followed up for efficacy for a minimum of 24 months and a maximum of 36 months following vaccination via regular visits and contacts to screen for possible TB. The primary endpoint is  incident cases of definite pulmonary TB disease in participants with clinical suspicion of pulmonary TB disease, with M.tb identified by at least two positive diagnostic tests (microbiological culture, Xpert MTB/RIF Ultra, or both) from sputum specimens taken before initiation of TB treatment and confirmed HIV-negative at the time of TB diagnosis, over a period starting 28 days following vaccination and lasting up to 36 months post vaccination.

KEMRI Centre for Respiratory Diseases Research (CRDR) aims to enroll at least 287 participants. Victoria Biomedical Research Institute (VIBRI) plans to enroll up to 287 participants at the Clinical Research Centres (CRCs) located at Kisumu County Referral Hospital in Kisumu County and Rachuonyo County Hospital in Homabay County. Enrollment for the study is competitive and the site can enroll more.