IAVI announces enrollment of cohort of people without tuberculosis (TB) infection in Phase 2b trial of TB vaccine candidate MTBVAC

IAVI is pleased to announce the first vaccination administered in a new cohort of participants in the IMAGINE clinical trial of the TB vaccine candidate MTBVAC. This cohort will enroll 1,200 participants who have never been exposed to Mycobacterium tuberculosis (M.tb), the bacterium that causes TB disease. Individuals in this new cohort will have a negative Interferon Gamma Release Assay (IGRA) blood test that measures immune memory to M.tb. A positive IGRA test result indicates TB infection, but not progression to TB disease. Enrollment will take place at 16 clinical research centers in South Africa, Kenya, and Tanzania. The initial vaccinations took place at TASK Delft in Cape Town, South Africa.

The IMAGINE trial is a Phase 2b, large-scale efficacy trial that will test the safety and immunogenicity of MTBVAC in adults and adolescents. The study, sponsored by IAVI, is funded by Coefficient Giving, the Gates Foundation, Wellcome, and the German Federal Ministry of Research, Technology and Space through the KfW Development Bank. The inclusion of M.tb unexposed participants in an IGRA negative cohort for safety and immunogenicity assessments will complement the IMAGINE trial’s initial enrollment cohort, which is seeking to enroll 4,300 participants with prior M.tb exposure (IGRA positive) but not TB disease, also referred to as people with TB infection or latent TB. Funding for the IGRA negative cohort was provided by an additional grant from Coefficient Giving.

MTBVAC is a single-shot vaccine delivered via intradermal delivery. It does not require an adjuvant and is well-suited for use in difficult-to-reach locations. MTBVAC was designed by the Spanish researcher Carlos Martin, from the University of Zaragoza, and Brigitte Gicquel, Ph.D., of Institut Pasteur, and was industrially developed and in-licensed by Biofabri (Zendal Group). It is the only live-attenuated TB vaccine candidate derived from M.tb in current trials. This is a notable difference from BCG, the only approved TB vaccine, which is derived from Mycobacterium bovis, the bovine form of tuberculosis.

The addition of 1,200 additional participants in the IMAGINE trial in an IGRA negative cohort could hold significant value for speeding the pathway to future licensure of MTBVAC. The expanded enrollment allows for robust safety and immunological data to be collected, which will be utilized for an assessment of whether MTBVAC is safe and immunogenic across IGRA negative and IGRA positive populations, and will allow for an assessment of immunologic markers of protection in a population with no known TB infection. While the trial is not powered to assess efficacy in people without TB infection (IGRA negative), immunological results will still strongly increase our understanding of how the vaccine would be expected to work in all populations.