A seamless, staged Phase II/III, open-label, multicenter, non-inferiority trial, to compare the efficacy and safety of 4 weeks of bedaquiline (BDQ) versus a a standard regimen for preventing regimen for preventing confirmed or probable tuberculosis disease (TBD) during 72 weeks of follow-up among people living with HIV (PLHIV) and high-risk Close Contacts (CC) of adults with Drug Susceptible (DS) or Rifampin Resistant (RR) TB.
A diagnosis of bacteriologically proven pulmonary TB
Initiated on treatment for pulmonary TB within the past 90 days
Have at least one close contact that is likely to be eligible for the study
On a dolutegravir-based or other approved integrase inhibitor antiretroviral therapy (ART) regimen that does not interact with bedaquiline or rifapentine.
Severe renal impairment (DAIDS Grade 4) or end-stage renal disease requiring hemodialysis or peritoneal dialysis
Severe hepatic impairment (Child-Pugh C)
Evidence of acute hepatitis, such as abdominal pain, jaundice, dark urine, and/or light stools within 90 days prior to enrollment
Severe cardiac arrythmia requiring medication
Parallel
Bedaquiline
DrugCCs (Close Contacts) of DS-TB Index Patients and PLHIV at high risk of developing TBD 1. Children 0 to \<5 years old who are HIV negative, regardless of latent tuberculosis infection (LTBI) result by TST (tuberculin skin test) or IGRA (interferon-gamma release assay) 2. Adults, pregnant people, adolescents, and children ≥5 years old who are HIV negative and LTBI positive (by IGRA) 3. Adults and adolescents ≥15 years of age who are living with HIV regardless of LTBI status, regardless of whether the participant is a CC CCs of RR-TB Index Patients at high risk of developing TBD 1. Children 0 to \<5 years old, regardless of HIV status or LTBI result (by TST or IGRA) 2. Adults, adolescents, and children ≥5 years old who are HIV negative and LTBI positive (by IGRA) 3. Adults, pregnant people, adolescents, and children ≥5 years old who are living with HIV regardless of LTBI status Bedaquiline based on weight and/or age at Enrollment daily for four weeks (28 doses)
Isoniazid, rifapentine
Combination productCCs of DS-TB Index Patients and PLHIV at high risk of developing TBD 1. Children 0 to \<5 years old who are HIV status negative, regardless of latent tuberculosis infection (LTBI) result (WHO-recommended skin test or interferon-gamma release assay \[IGRA\]) 2. Adults, adolescents, and children ≥5 years old who are HIV status negative and LTBI positive (by IGRA) 3. Adults and adolescents ≥15 years of age who are living with HIV regardless of LTBI status, regardless of whether they are a CC 3HP: 3 months of weekly isoniazid (H) and rifapentine (P) (12 doses)
Levofloxacin
DrugCCs of RR-TB Index Patients at high risk of developing TBD 1. Children 0 to \<5 years old, regardless of HIV status or LTBI result (by TST or IGRA) 2. Adults, adolescents, and children ≥5 years old who are HIV status negative and LTBI positive (by IGRA) 3. Adults, pregnant people, adolescents, and children ≥5 years old who are living with HIV regardless of LTBI status Levofloxacin (LFX) based on weight at Enrollment daily for 6 months (182 doses)
Safety DS-TB CCs and PLHIV (Stage 1): Proportion of participants who permanently discontinue the randomized study drug due to a treatment-related adverse event by 18 weeks
Estimate of the safety of 1BDQ and 3HP among adult, adolescent, and child CCs of DS-TB Index Patients at high risk of developing TBD, as well as adult and adolescent PLHIV in high TB-burden settings
Safety for RR-TB CCs (Stage 1): Proportion of participants who permanently discontinue the randomized study drug due to a treatment-related adverse event by 36 weeks
Estimate of the safety of 1BDQ and 6 months of levofloxacin (6L) among adult, adolescent, and child CCs of RR-TB Index Patients at high risk of developing TBD
Treatment Completion - PLHIV & CCs of DS-TB (Stage 1): Proportion of participants completing assigned treatment within window prescribed in protocol
Estimate on-time treatment completion of 1BDQ \& 3HP in adult, adolescent, \& child CCs of DS-TB Index Patients at high risk of developing TBD, \& adult and adolescent PLHIV in high TB-burden countries
Treatment Completion - CCs of RR-TB (Stage 1): Proportion of participants completing assigned treatment within window prescribed in protocol
Estimate on-time treatment completion of 1BDQ and 6 months of levofloxacin (6L) among adult, adolescent, and child CCs of RR-TB Index Patients at high risk of developing TBD
Stage 1: Proportion of participants who permanently discontinue the randomized study drug due to a treatment-related adverse event by 18 weeks
To compare the safety of 1BDQ to 3HP among adult, adolescent, and child CCs of DS-TB Index Patients at high risk of developing TBD as well as adult and adolescent PLHIV in high TB-burden settings
Stage 1: Proportion of participants who permanently discontinue the randomized study drug due to a treatment-related adverse event by 36 weeks
To compare the safety of 1BDQ to 6 months of levofloxacin (6L) among adult, adolescent, and child CCs of RR-TB Index Patients at high risk of developing TBD
Stage 1: Proportion of participants completing assigned treatment within window prescribed in protocol
To compare on-time treatment completion of 1BDQ to 6 months of levofloxacin (6L) among adult, adolescent, and child CCs of RR-TB Index Patients at high risk of developing TBD
Stage 1: Proportion of individuals who experience a grade 3 or higher AE, compared between the comparator arm and investigational (1BDQ) arm at 18 weeks
To compare the safety of 1BDQ to 3HP among adult, adolescent, and child CCs of DS-TB Index Patients at high risk of developing TBD, as well as adult and adolescent PLHIV in high TB-burden settings
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Johns Hopkins University
Lead sponsor
Elizabeth Glaser Pediatric AIDS Foundation
Collaborator
US Department of State
Collaborator