Despite these recent advances, there remains a pressing need to develop new and highly effective regimens for the treatment of TB that have broad activity (capable of treating both rifampicin- susceptible and resistant organisms) and that may permit a significant reduction in the duration of treatment (e.g., to ≤ 4 months).
This randomized, open-label, multi-center, seamless Phase 2B (regimen selection) and 2C(treatment duration), multi-arm, multi-stage, Platform clinical Trial, evaluates multiple regimens and durations of treatment in pulmonary tuberculosis (TB).
The main aim is to identify novel drug regimen(s) with acceptable safety profile, non-inferior efficacy and shortened treatment duration compared to the standard-of-care 24-week HRZE regimen that could be used to treat people with rifampicin susceptible and rifampicin resistant TB.
In stage 1 the new drug combinations will first be compared to the established standard-of-care (SOC) first-line drug combination. Each new drug combination will be taken for a period of 4 months and the established treatment combination will be taken for a usual period of 6 months. The drug combinations that look most promising in the “phase 2B trial” will then advance to the second stage for testing in a new group of people with drug-susceptible TB.
The adaptive trial approach used in the PARADIGM4TB (UNITE4TB-01) trial is new and innovative. Integrating 2 stages, the phase 2B and phase 2C, within the same trial, will minimise the long delays arising from testing combinations in separate trials.
Expected impact: Safe and efficacious new TB treatment options with shorter duration for drug-susceptible and drug-resistant TB.
