A5362: A Phase IIc Trial of Clofazimine- and Rifapentine-Containing Treatment Shortening Regimens in Drug-Susceptible Tuberculosis: The CLO-FAST Study

A5362 is a study for people with pulmonary tuberculosis (TB) without evidence of resistance to the TB drugs isoniazid (INH) or rifampin (RIF). Participants will be enrolled in one of three treatment groups. Duration of treatment will vary depending on which treatment group the participant is enrolled, but all participants will be in the study for 65 weeks.

• To determine if taking a shorter 3-month regimen of a new combination of TB drugs is better than taking a 6-month regimen that is standard of care for the treatment of TB.
• To look at the tolerability of the study drugs, the effect the drugs have on the electrical activity of the heart, and will measure the level of these drugs in blood.

People who:

• Are 18 years of age or older
• Have pulmonary TB with or without history of prior treatment, and without known resistance of INH or RIF
• Have a normal chest X-ray at screening
• For participants living with HIV: CD4 cell count ≥100 and taking or planning to take anti-HIV therapy
• Not more than 5 days of treatment directed against active TB for the current TB episode

For this three-arm study, participants will receive treatment in either:

Arm 1

Rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) high dose for 2 weeks; then PHZE + CFZ standard dose for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ standard dose 5 weeks, for a total of 13 weeks of study treatment.

Arm 2 (Standard of Care)

Rifampin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampin/isoniazid (RH) for 18 weeks, for a total of 26 weeks of study treatment.

Arm C

PHZE + CFZ standard dose for 4 weeks; switch to standard of care, completing RHZE for 4 weeks; then RH for 18 weeks.

All participants will have blood samples taken to measure the amount of anti-TB drugs in the body, and pictures taken to look for changes in skin color. All participants will undergo routine safety monitoring.  Participants will be followed in the study for 65 weeks.

Study TB medications are provided by the study. Antiretroviral medications are not provided by the study.