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.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
β. 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.
β. 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.
β. Documentation of HIV-1 infection status, as below:
β. For individuals with HIV: CD4+ cell count β₯100 cells/mm3 based on testing performed within 30 days prior to study entry.
β. For individuals with HIV: Currently being treated with dolutegravir-based antiretroviral therapy (ART), or plan to initiate dolutegravir-based ART at or before study week 8.
β. Individuals age β₯18 years.
β. The following laboratory values obtained within 7 days prior to study entry at any network-approved non-U.S. laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs:
What they're measuring
1
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
Timeframe: Weeks 0, 1, 2, 3, 4 and 6
2
Difference in the cumulative proportion of participants having at least one new Grade 3 or higher adverse event (AE) by week 8 of treatment
Timeframe: 8 weeks
Trial details
NCT IDNCT06192160
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
. For female study candidates who are of reproductive potential, negative pregnancy test (urine HCG or serum Ξ²-HCG) within 3 days (72 hours) prior to entry by any network-approved non-U.S. laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs.
Exclusion criteria
β. More than cumulative 7 days of treatment directed against active TB for the current TB episode in the 60 days preceding study entry.
β. Current extrapulmonary TB, in the opinion of the investigator.
β. QTcF interval \>450 ms within 7 days prior to study entry.
β. History of or ongoing heart failure.
β. Personal or family history of congenital QT prolongation.
β. History of known, untreated, ongoing hypothyroidism.