01.08.2025
UNITE4TB flagship trial completes first wave recruitment
Tuberculosis (TB) is a major threat to public health and is among the leading causes of death worldwide, according to the World Health Organization. The emergence of drug-resistant TB and current standard of long treatment regimens have increased the urgent need for new, more effective therapies. The multi-arm multi-stage flagship PARADIGM4TB (UNITE4TB-01) trial, part of the UNITE4TB consortium, is testing 14 drug regimens to accelerate development of new treatments for TB.
UNITE4TB (academia and industry united innovation and treatment for tuberculosis) is the largest public-private partnership focused on clinical TB drug development in the history of the European Union, with representation from academic institutions, small- and medium-sized enterprises (SMEs), public organizations, and pharmaceutical companies.
PARADIGM4TB (UNITE4TB-01) has successfully completed recruitment for the first stage of the trial evaluating an initial 10 drug regimens. The 400th participant was enrolled on 17 July 2025, marking a significant milestone for the TB research community. This achievement reflects the dedication of the trial teams and the trust of the trial participants.
PARADIGM4TB is a multi-arm, multi-stage Phase 2 platform trial within the UNITE4TB Consortium, designed to evaluate multiple drug combinations and treatment durations for pulmonary TB. The trial is assessing whether new TB drug regimens are at least as safe and effective as current treatments. It is also exploring the potential for shorter treatments that can also benefit a wider range of people with TB, including those with drug-resistant TB.
As a platform trial, PARADIGM4TB allows for the introduction of new drugs as they become available. The first “regimen selection” stage includes two waves to assess the effectiveness and safety of fourteen combination regimens, all administered for 16 weeks, and containing at least one new drug combined with already licensed medications. The first wave includes ten regimens containing ganfeborole (a leucyl‑tRNA synthetase inhibitor) developed by GSK and/or BTZ‑043 (a DprE1 inhibitor) developed by LMU University Hospital Munich. The second wave, set to start in August 2025, will include four regimens which feature quabodepistat (another DprE1 inhibitor) developed by Otsuka and delpazolid (an oxazolidinone) developed by LigaChemBio. The licensed TB drugs being used in PARADIGM4TB regimens are bedaquiline, delamanid/pretomanid, linezolid, moxifloxacin, and pyrazinamide.
Contact
Prof. Dr. med. Dr. h.c. Christoph Lange
DZIF TTU TB (ClinTB)
T +49 4537 / 188-3010 (Sekretariat)
F +49 4537 / 188-6030
clange@fz-borstel.de
The most promising drugs combinations from the first regimen selection wave will advance into a “duration-selection” stage, which will find the optimal length of therapy by studying treatment durations ranging from 8 to 20 weeks. The most effective regimen(s) with the right duration can be then be taken forward to separate, large-scale Phase 3 trials, an essential step before they can be implemented in clinical practice worldwide.
Thanks to its adaptive and efficient trial design, PARADIGM4TB can identify the most effective and safest drug combinations more quickly, accelerating progress towards shorter and more manageable TB treatments. The PARADIGM4TB trial launched in January 2024 and, so far, it has enrolled participants across 14 sites in South Africa, Tanzania, Uganda, Vietnam and Moldova. With the planned expansion of the trial in 2025 and 2026, PARADIGM4TB will be active in over 30 sites across four continents.
PARADIGM4TB is sponsored by the MRC Clinical Trials Unit at UCL, and is part of UNITE4TB, the largest collaboration between academic partners and pharmaceutical companies working together to speed up the development of new tuberculosis treatments. This is a very important milestone achievement sys Professor Christoph Lange, Medical Director of the Research Center Borstel and Clinical Lead of the UNITE4TB project.
Further Information: