A5397/HVTN 603:A Phase 2a/2b Study Evaluating Safety, Immunogenicity, and Therapeutic Efficacy of ID93 + GLA-SE Vaccination in Participants with Rifampicin-Susceptible Pulmonary TB

Effective tuberculosis (TB) treatment is available and saves millions of lives, but it has not had a significant impact on the global TB epidemic. The treatment requires strict adherence to taking the medicine on schedule, and if it isn’t taken as directed people can relapse before they complete treatment. TB can recur in up to 8% of people who successfully complete TB treatment. Having an effective TB vaccine to prevent TB infection and control TB disease is essential to eliminate TB globally.

A5397/HVTN 603 will give participants 2 injections of a study vaccine called ID93+GLA-SE or a placebo at different times after they have started taking TB treatment. The researchers will compare responses in people who get the study vaccine to people who get the placebo. This study will enroll both people with and without HIV. It is the first to test ID93 + GLA-SE in people living with HIV (PLWH).

• To see if the study vaccine (ID93 + GLA-SE) is safe.
• To look at differences in immune system responses depending on the timing of giving the injections after people start using standard TB treatment.
• To see if getting the study vaccine in addition to TB treatment reduces bad TB outcomes.

People aged 18 years or older who:

• Have pulmonary TB that is sensitive to certain TB medications.
• Do not have drug resistant TB and have not been treated for TB previously.
• Started standard TB treatment (per local guidelines) within the past 7 days.
• Are living with or without HIV. (For PLWH: taking HIV treatment for at least 90 days with an undetectable viral load and a CD4 count at least 250)

Participants with TB who are receiving locally provided TB treatment according to the standard of care will be randomized to receive the study vaccine or placebo on one of 4 different schedules. They will continue to use TB treatment during the study. PLWH will also continue to use their HIV treatment throughout the study. Each group will be evaluated on the safety of a two-dose ID93 + GLA-SE vaccine regimen or placebo administered 60 days apart at 1, 2, 3, or 4 months following the initiation of TB treatment.

The ID93 + GLA-SE study vaccine and placebo injections will be provided by the study, but TB treatment and HIV treatment are not provided. Participants will continue to receive these medications and associated healthcare in the community through their usual providers.

Participants may be in the study for up to 18 months. They will be followed for a minimum of one year following completion of TB treatment.