A new dawn in the fight against Tuberculosis
UNITE4TB, the largest public-private collaboration in tuberculosis drug development, announces start of clinical trials.
Today, UNITE4TB, an international public-private partnership striving to fast-track the development of innovative tuberculosis (TB) treatments, announced the start of its phase-IIb/c-clinical trial programme with the first participant enrolled at its trial site in Cape Town, South Africa. The announcement is a major milestone for the project and the tuberculosis community as a whole, helping to advance tuberculosis science and to enhance the efficiency with which new treatments are delivered.
The tuberculosis challenge
Tuberculosis (TB) is a major threat to public health, being among the leading causes of death worldwide. According to the World Health Organisation, the disease claimed 1.3 million lives in 2022, making it the second leading infectious killer after COVID-19. Drug-resistant TB and long treatment regimens have increased the urgency for action and investment in TB research.
For people affected by TB, the most important outcome is rapid access to better regimens of shorter treatment duration and with fewer side effects. UNITE4TB is engaging with key societal stakeholders to ensure that its novel regimens will be made available as efficiently as possible.
Exploring new frontiers
UNITE4TB’s innovative phase-IIb/c-trials will test 14 combinations of nine existing drugs, as well as two newly developed drug candidates (BTZ-043 and GSK656). The ultimate aim is to create regimens that can further improve multidrug-resistant (MDR) treatment and also be effective for drug-sensitive TB.
The German Center for Infection Research (DZIF) and its member institution LMU University Hospital Munich are playing a central role in the UNITE4TB consortium. The LMU University Hospital Munich is the sponsor of one of two UNITE4TB clinical trials, DECISION (BTZ-043 Dose Evaluation in CombInation and SelectION), which is coordinated and overseen by the Division of Infectious Diseases and Tropical Medicine at LMU University Hospital Munich. DECISION (UNITE4TB-02) is a phase-IIb, dose-finding study comparing the safety and efficacy of different doses of BTZ-043 administered with a backbone of bedaquiline and delamanid in participants with drug-sensitive tuberculosis.
UNITE4TB’s explorative regimens have been constructed by combining the novel compounds BTZ-043 and GSK656 with the most recently licensed drug classes—diarylquinoline (bedaquiline) and nitroimidazoles (delamanid or pretonamid). Apart from the DECISION study, the UNITE4TB trial programme includes PARADIGM4TB, a phase-IIB/C platform trial to evaluate multiple regimens and durations of treatment in pulmonary tuberculosis. PARADIGM4TB will establish which fourth drug (either moxifloxacin, linezolid, or pyrazinamide) can be added as the optimal component to a bedaquiline, delamanid, BTZ-043 or GSK656 regimen. The trial will also explore the efficacy of a totally new combination of BTZ-043 and GSK656 together with bedaquiline and delamanid.
About BTZ-043
BTZ-043 is the first antibiotic to be developed in Germany in decades. It was discovered by researchers at the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI) in Jena. Since 2014, the Leibniz-HKI and the Tropical Institute at the LMU University Hospital Munich have joined forces in a research collaboration to advance the preclinical development of the novel compound. "The drug candidate belongs to a new class of antibiotics. It inhibits an enzyme in tuberculosis pathogens that is needed to build the bacterial cell wall," says Professor Axel Brakhage, director of the Leibniz-HKI in Jena. "This inhibition causes the cell to dissolve and ultimately the pathogen to die."
By the time the second phase of clinical development is completed, the project will have cost about 60 million euros. The German Federal Ministry of Education and Research (BMBF) is providing around 50 percent of this funding either directly or through the German Center for Infection Research (DZIF). Further funding is provided by the European-African "European & Developing Countries Clinical Trials Partnership" (EDCTP), the European "Innovative Medicines Initiative" (IMI), the Bavarian State Ministry of Science and the Arts, and the Free State of Thuringia.
Expert insights
Commenting on the trial design, UNITE4TB Scientific Leader, Prof. Michael Hoelscher of LMU University Hospital Munich and coordinator of the DZIF research area Tuberculosis said: “There are three major steps in TB regimen development: the establishment of the optimal dose for each individual drug, the identification of the right combination of four different drugs and the shortest possible treatment duration of the regimen of choice. In UNITE4TB, we are addressing these aspects via the most efficient trial designs possible.”
The South African trial site, part of the clinical research institute TASK, where the first participant in the UNITE4TB trial programme has been enrolled, is one of several selected for the project. The sites were chosen based on TB prevalence. Other high-burden countries on the trial site list include Tanzania, Uganda, Vietnam, and the Philippines.
Prof. Andreas Diacon, Chairman and CSO TASK and CEO TASK Europe, said: “At TASK, we conduct all stages of clinical trials, from first in human trials all the way through to licensing. We are thrilled to be kicking off the UNITE4TB clinical trial programme here in Cape Town and are proud to be part of this important clinical research project."
Reflecting on this latest milestone, Prof. Martin Boeree, UNITE4TB project coordinator from Radboudumc said: “Today’s announcement marks an exciting moment for TB research. The world needs new drugs for TB but also new ways to run clinical studies. Our public-private partnership sets a new standard in this regard. If successful, our work will deliver a new treatment regimen of shorter duration that can be used to fight all types of tuberculosis.”
For more details on the clinical studies, please see the press release of the UNITE4TB Consortium. A video on the UNITE4TB Phase-IIb/c-clinical trial programme can be found here.
