A5409/RAD-TB is an adaptive Phase 2 randomized, controlled, open-label, dose-ranging, platform protocol to evaluate the safety and efficacy of multidrug regimens for the treatment of adults with drug-susceptible pulmonary tuberculosis (TB).
A5409 hypothesizes that novel regimens for the treatment of pulmonary tuberculosis will result in superior early efficacy, as determined by longitudinal mycobacteria growth indicator tube (MGIT) liquid culture time to positivity (TTP) measurements over the first 6 weeks of treatment, and will have acceptable safety and tolerability over 8 weeks of treatment relative to standard of care \[(SOC) isoniazid/rifampicin/pyrazinamide/ethambutol (HRZE)\].
The study will run for 52 weeks, inclusive of 26 weeks of TB treatment comprised of 8 weeks of study treatment (experimental or SOC, based on treatment arm assignment) followed by 18 weeks of SOC continuation phase treatment with 45 participants in each experimental treatment arm and at least 90 participants in the SOC arm.
Pulmonary TB (among individuals either without history of prior TB treatment or with history of TB treatment completed more than 2 years prior to study entry), identified within 7 days prior to study entry by at least one sputum specimen positive for Mtb by Xpert. Semiquantitative Mtb results of "medium" or "high" from Xpert MTB/RIF Ultra are required.
Pulmonary TB with documented INH susceptibility (by Line Probe Assay (LPA) or Xpert MTB/XDR or other validated molecular test) and with documented RIF susceptibility (by LPA or Xpert MTB/RIF or Xpert MTB/RIF Ultra or other validated molecular test) within 7 days prior to study entry.
A second antibody test from different manufacturers or based on different principles and epitopes (combination antigen-antibody-based rapid tests may be used), or
HIV-1 antigen, or
More than cumulative 7 days of treatment directed against active TB for the current TB episode in the 60 days preceding study entry.
Current extrapulmonary TB, in the opinion of the investigator.
QTcF interval >450 ms within 7 days prior to study entry.
History of or ongoing heart failure.
Parallel
Isoniazid
DrugINH 300 mg will be administered as one tablet orally once daily.
Rifampicin
DrugRIF 600 mg will be administered as two 300 mg capsules orally once daily on an empty stomach, 1 hour before or 2 hours after eating a meal.
Pyrazinamide
DrugPZA will be administered as 500 mg tablets, based on weight, orally once daily.
Ethambutol
DrugEMB will be administered as 400 mg tablets, based on weight, orally once daily.
Bedaquiline
DrugBDQ 400 mg will be administered as four 100 mg tablets orally once daily with a meal for the first 2 weeks followed by 200 mg (two 100 mg tablets) orally once daily with a meal for 6 weeks.
Pretomanid
DrugPa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
Linezolid
DrugLZD 600 mg will be administered as one 600 mg tablet orally once daily.
TBI-223
DrugTBI-223 2400 mg once daily will be administered as four 600 mg tablets orally once daily with a meal.
Sutezolid
DrugSZD 1600 mg once daily will be administered as four 400 mg tablets orally once daily with a meal.
TBI-223
DrugTBI-223 1200 mg once daily will be administered as two 600 mg tablets orally with a meal.
Sutezolid
DrugSZD 800 mg once daily will be administered as two 400 mg tablets orally once daily with a meal.
6
Treatment groupsSee each treatment group below.
Difference in mean log10 (Time to positivity (TTP)) slope from longitudinal mycobacteria growth indicator tube (MGIT) liquid culture measurements over the first 6 weeks of treatment
for each experimental treatment arm compared to the SOC treatment arm.
Difference in the cumulative proportion of participants having at least one new Grade 3 or higher adverse event (AE) by week 8 of treatment
for each experimental treatment arm compared to the SOC treatment arm.
Cumulative proportion of participants with stable sputum culture conversion by week 8 as measured by culture-negative status via MGIT liquid culture at two consecutive measurements.
Mean log10 TTP slope from longitudinal MGIT liquid culture measurements over the first 8 weeks of treatment.
Cumulative proportion of participants with a new Grade 3 or higher AE by week 26 of treatment.
Cumulative proportion of participants with permanent discontinuation of study-provided anti-TB drugs due to any reason prior to Week 8 of treatment.
Click on the lead sponsor to view all of their trials.
National Institute of Allergy and Infectious Diseases (NIAID)
Lead sponsor
TB Alliance
Collaborator