New hope in the fight against tuberculosis

The LMU Klinikum München is the clinical sponsor of one of the two UNITE4TB studies, DECISION (BTZ-043 Dose Evaluation in CombInation and SelectION), i.e. the Department of Infectious Diseases and Tropical Medicine is coordinating and monitoring patient safety. In DECISION (UNITE4TB-02), the optimal dosage of BTZ-0431 in combination with two other TB drugs, bedaquiline and delamanid, is to be tested in terms of safety and efficacy. The correct dose is the prerequisite for further studies on the optimal drug combination and duration of therapy.

Tuberculosis is a major public health challenge and one of the leading causes of death worldwide. In 2021, the disease claimed 1.6 million lives, making it the second most common infectious cause of death after COVID-19.2 The emergence of antibiotic resistance and the problem of long treatment duration have led to increased investment and research activities in the field of tuberculosis.

It is crucial for people with tuberculosis to have faster access to improved therapies with shorter treatment duration and fewer side effects. UNITE4TB has therefore been working with key social stakeholders since the start of the project in order to make newly developed therapies available as efficiently as possible at a later date.

The innovative phase 2b/c studies of UNITE4TB are testing 14 combinations of nine existing drugs as well as two newly developed drug candidates (GSK-656 and BTZ-043). The aim is to develop treatment regimens that can further improve the treatment of multidrug-resistant (MDR) and drug-sensitive tuberculosis.

The regimens being investigated within UNITE4TB have been developed by combining the novel agents GSK656 and BTZ-043 with the most recently approved drug classes diarylquinoline (bedaquiline) and nitroimidazoles (delamanid or pretonamide). In addition to the DECISION study, the UNITE4TB study program includes PARADIGM4TB, a phase 2b/c platform study for the clinical evaluation of different treatment regimens and durations in pulmonary tuberculosis. PARADIGM4TB will test which fourth drug (either moxifloxacin, linezolid or pyrazinamide) can be added as an optimal component to a bedaquiline, delamanid, BTZ-043 or GSK656 regimen. The study will also investigate the efficacy of a completely new combination of GSK656 and BTZ-043 together with bedaquiline and delamanid.

The scientific director of the UNITE4TB study, Prof. Dr. med. Michael Hoelscher, Director of the Department of Infectious Diseases and Tropical Medicine at LMU Klinikum München, explains the study design:"There are three important steps in the development of tuberculosis regimens: determining the optimal dose for each individual drug, identifying the right combination of four different drugs and the shortest possible treatment duration of the regimen of choice. In UNITE4TB, we are investigating these aspects with the most efficient trial design possible."

The South African trial site at the TASK Clinical Research Institute, where the first participant in the UNITE4TB trial was enrolled, is one of several sites selected for the project. The sites were selected based on the prevalence of tuberculosis. Other study sites include Tanzania, Uganda, Vietnam and the Philippines.

Prof. Andreas Diacon, Chairman and CSO of TASK and CEO of TASK Europe, said:"At TASK we conduct all phases of clinical trials, from initial human trials through to licensing. We are very excited about the launch of the UNITE4TB clinical trial program here in Cape Town and are proud to be part of this important clinical research project."

Prof. Martin Boeree, UNITE4TB project coordinator from Radboudumc, commented on the study launch:"Today is a special moment for TB research. The world needs new drugs against tuberculosis, but also new ways to conduct clinical trials. Our collaboration between academic and private sector partners sets a new standard in this regard. If the project is successful, it will produce a new, shorter treatment regimen that can be used to fight all types of tuberculosis."