A5409: A Phase 2 Randomized, Adaptive, Dose-Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis (RAD-TB)

The standard of care (SOC) treatment of tuberculosis (TB) was developed over 40 years ago, and the treatment is long (6 months) and hard. In many settings, the medicine does not work well because people stop taking it or miss doses, which leads to TB returning. For some people, the SOC treatment can cause negative side effects.

This study will evaluate new medication regimens for the treatment of TB. This study is adaptive, which means, as new medication regimens are identified for the treatment of TB, some of them will be selected for testing in this study. Therefore, there may be different drug regimens being used as part of the study at different times.

• To see if various experimental medication regimens for the treatment of drug-susceptible pulmonary TB are safe and whether they work better than the SOC TB treatment.

• Age 18 years or older
• Living with or without HIV
• Have TB infection (in persons who have never had TB) that is confirmed by a laboratory test within 7 days before study entry
• Have pulmonary TB that is sensitive to certain TB medications

At study entry, participants will be randomly assigned (like flipping a coin or rolling dice) to one of six treatment arms (five experimental arms and one SOC arm, with twice the allocation).

The study regimen provided will be either an experimental TB drug regimen or the current SOC TB treatment.

Participants will be in this study for about 52 weeks. This includes a total of 26 weeks of TB treatment. If assigned to the experimental arm, participants will have 8 weeks of experimental treatment, followed by 18 weeks of SOC treatment. If assigned to the SOC arm, participants will have 26 weeks of SOC treatment.