The A5414 study will evaluate whether treatment for drug-susceptible pulmonary tuberculosis (TB) can be tailored according to a participant's risk of an unfavorable outcome. Participants will be assigned to lower-risk or higher-risk groups using baseline characteristics and then randomized within each group to receive either standard TB treatment or an investigational rifapentine- and moxifloxacin-containing regimen. The study will evaluate whether shorter treatment durations may be used in lower-risk participants and whether the investigational regimen may improve outcomes in higher-risk participants. Safety and tolerability will also be evaluated.
Has pulmonary tuberculosis (TB) that is likely to respond to standard TB medicines (drug-susceptible TB), based on sputum testing done within 7 days before entering the study. The test must show Mycobacterium tuberculosis is present, with no rifamycin resistance detected and no known resistance to isoniazid or fluoroquinolones.
Has a SPECTRA-TB risk score and risk group assigned during screening using the study-specific calculator.
Has a Karnofsky performance score of 50 or higher within 30 days before entering the study.
Has documented HIV-1 status (either with HIV or without HIV) based on acceptable testing.
TB bacteria are known to be resistant to 1 or more of the following medicines: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones.
Received more than 5 days of treatment for active TB within the 24 weeks before study entry.
Received more than 5 days of treatment within the 30 days before study entry with certain TB medicines or related antibiotics, including isoniazid, rifampin, rifapentine, ethambutol, moxifloxacin, pyrazinamide, aminoglycosides, fluoroquinolones, linezolid, bedaquiline, pretomanid, and other specified anti-TB drugs.
Has suspected or confirmed TB involving the brain or central nervous system, bones, joints, heart lining (pericardium), or miliary TB.
Parallel
Isoniazid
DrugAdministered orally once daily
Rifampin
DrugAdministered orally once daily
Pyrazinamide
DrugAdministered orally once daily
Ethambutol
DrugAdministered orally once daily
Rifapentine
DrugAdministered orally once daily
Moxifloxacin
DrugAdministered orally once daily
8
Treatment groupsSee each treatment group below.
Lower-risk group: Proportion of participants with sustained cure at 52 weeks after randomization
Sustained cure is defined as: participant known to be alive at or after 52 weeks after randomization; sustained culture negativity at 52 weeks after randomization, defined as the last 2 liquid cultures collected at different visits being Mtb-negative without an intervening Mtb-positive result, with the last collected no earlier than 48 weeks after randomization; no treatment failure or relapse through 52 weeks after randomization; and no retreatment or additional TB treatment beyond assigned study treatment through 52 weeks after randomization. Participants will be classified as having presence of sustained cure, absence of sustained cure, or not assessable.
Lower-risk group: Proportion of participants with at least 1 new Grade 3 to 5 adverse event through 28 weeks after randomization
Occurrence of at least 1 new Grade 3 to 5 adverse event during the 28 weeks following randomization among participants in the lower-risk group, where 28 weeks is 2 weeks beyond the longest scheduled treatment duration of 26 weeks.
Higher-risk group: Proportion of participants with sustained cure at 52 week after randomization
Sustained cure is defined as: participant known to be alive at or after 52 weeks after randomization; sustained culture negativity at 52 weeks after randomization, defined as the last 2 liquid cultures collected at different visits being Mtb-negative without an intervening Mtb-positive result, with the last collected no earlier than 48 weeks after randomization; no treatment failure or relapse through 52 weeks after randomization; and no retreatment or additional TB treatment beyond assigned study treatment through 52 weeks after randomization. Participants will be classified as having presence of sustained cure, absence of sustained cure, or not assessable.
Higher-risk group: Proportion of participants with at least 1 new Grade 3 to 5 adverse event through 28 weeks after randomization
Occurrence of at least 1 new Grade 3 to 5 adverse event during the 28 weeks following randomization among participants in the higher-risk group, where 28 weeks is 2 weeks beyond the longest scheduled treatment duration of 26 weeks.
Proportion of participants with sustained cure at 72 weeks after randomization
Sustained cure defined as for the primary efficacy outcome measure, except assessed with respect to 72 weeks.
Cumulative proportion of stable liquid mycobacterial culture conversion by 26 weeks after randomization
Stable culture conversion is defined as two negative cultures on two different days without an intervening positive culture (irrespective of positive cultures subsequent to stable culture conversion).
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National Institute of Allergy and Infectious Diseases (NIAID)
Lead sponsor
ViiV Healthcare
Collaborator
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