Trial to evaluate multiple regimes, durations of treatment for TB - "PARADGM4TB"

Ifakara Health Institute is implementing a 5-year clinical trial project titled PARADGM4TB, aiming to revolutionize the treatment of pulmonary tuberculosis (TB). Sponsored by University College London (UCL), this study seeks to evaluate multiple drug regimens and treatment durations to improve patient outcomes.

Overview of the trial
The PARADGM4TB project will be conducted at Mwananyamala Hospital in Tanzania, and at other sites in South Africa and Tanzania. Key implementing partners include MMRC, NIMR-Mwanza, and KCRI.

Led by Dr. Huglin Beno of the Ifakara Health Institute, the study will benefit from his leadership and collaboration with colleagues.

The trial will employ a seamless Phase 2B/2C design, allowing for a continuous evaluation of multiple treatment options. The objective is to identify drug regimens that offer a shorter, safer, and equally effective alternative to the current standard TB treatment.

Key goals of PARADGM4TB

1. 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/HR regimen that could be used to treat both rifampicin-susceptible and resistant TB.
2. 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/HR regimen that could be used to treat both rifampicin-susceptible and resistant TB.
3. Amongst regimens selected for progression from Phase 2B, to further evaluate the safety profile and to identify the optimal treatment duration (between 8 and 16 weeks) based on unfavorable outcomes to support advancement to future Phase 3 trials.

Trial phases, milestones
The initial Phase of the study is set to conclude by 2025, involving 23 participants, and aims to assess the feasibility of reducing treatment to 16 weeks. The recruitment of participants will occur between 2024 and 2025 and will be monitored for up to 72 weeks to evaluate long-term safety and efficacy.

The trial will include approximately 12 arms, testing various drug combinations to determine the most effective and patient-friendly treatment plan. By targeting both rifampicin-susceptible and rifampicin-resistant TB strains, the study aims to broaden the scope of treatment options available for TB management.

PARADGM4TB study is a step forward in global efforts to combat TB. With its innovative approach to reducing treatment duration and improving patient safety, this trial has the potential to reshape the future of TB care and save countless lives worldwide.

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