Recruitment for tuberculosis study completed

| by Friederike Gawlik

Doctoral student François Keiff, who was involved in the latest BTZ study, is looking at a test tube in the laboratory, which he is holding up. He is wearing a lab coat and blue rubber gloves.
Together with other colleagues, doctoral student François Keiff has discovered that modifying the C-6 position of BTZ compounds, active against tuberculosis, reduces the production of unfavorable metabolites. Photo: Anna Schroll/Leibniz-HKI

The Leibniz-HKI is pleased to announce the successful recruitment of participants for the DECISION study of the international UNITE4TB consortium, which is investigating new treatment regimens to combat drug-resistant tuberculosis. This represents a significant milestone in the fight against this deadly disease.

Tuberculosis is a bacterial infection caused by Mycobacterium tuberculosis, which usually affects the lungs. If left untreated, the disease can be fatal, especially in developing countries where access to diagnosis and treatment is often limited. To make matters worse, the number of resistant pathogens is increasing – currently available antibiotics are no longer effective. According to the WHO, around 10 million people worldwide are newly infected with tuberculosis every year, of whom around 1.6 million die. Tuberculosis is therefore one of the most common and deadliest infectious diseases. New drugs against antibiotic-resistant strains of bacteria are urgently needed.

For some years now, an active compound has been raising high hopes for treatment: BTZ-043, a new antibiotic from the group of nitro-benzothiazinones (BTZs), which was discovered by researchers at the Leibniz-HKI and has been under development since 2014 in collaboration with colleagues from the Institute of Infectious Diseases and Tropical Medicine at LMU Hospital Munich and other partners such as Hapila GmbH in Gera. BTZ-043 is the first tuberculosis antibiotic to be developed in Germany in decades and currently the only one tested in clinical trials. The active compound belongs to a new class of antibiotics that inhibit an enzyme in the tuberculosis pathogens that is necessary for building the bacterial cell wall. The novel antibiotic, which was named Leibniz Drug of the Year in 2023, is also effective against drug-resistant strains of M. tuberculosis.

To be seen is a graphic drawing of the molecular structure of the active compound BTZ-043, the only antibiotic against tuberculosis discovered in Germany that is currently undergoing clinical trials.
The molecular structure of the active compound BTZ-043, the only antibiotic against tuberculosis discovered in Germany that is currently undergoing clinical trials. Source: Florian Kloß

The drug development, which costs several million euros, is only possible thanks to joint funding from the public and private sectors: the two research consortia InfectControl and the German Center for Infection Research (DZIF), which are funded by the Federal Ministry of Education and Research (BMBF), are particularly involved in drug development. The clinical trials are taking place as part of the European-African consortium PanACEA II, funded by the European & Developing Countries Clinical Trials Partnership (EDCTP), and the research consortium “Academia and Industry United Innovation and Treatment for Tuberculosis” (UNITE4TB).

UNITE4TB is currently testing the drug as part of the DECISION study (BTZ-043 Dose Evaluation in CombInation and SelectION), which is coordinated and monitored by the Tropical Institute in Munich and sponsored by LMU Hospital Munich. DECISION is a clinical trial at an advanced stage of testing comparing the safety and efficacy of different BTZ-043 doses in patients with drug-susceptible tuberculosis. To this end, 90 participants have now been recruited at four sites in South Africa and Tanzania. “The results will help to determine the correct dose of BTZ-043 and thus make an important contribution to the global fight against tuberculosis,” says Prof. Dr. med. Michael Hoelscher, Director of the Tropical Institute at the LMU Hospital in Munich. “We are very pleased to have completed recruitment for the DECISION study. This success underlines the commitment and hard work of our global UNITE4TB team and our local study partners.”

Leibniz-HKI researchers want to further optimize the active substance

Photo of a poster showing the many phases of clinical testing that BTZ-043 must undergo before it can be used as a drug against tuberculosis.
BTZ-043 must undergo many phases of clinical trial before the active compound can be used as a drug against tuberculosis. Photo: Anna Schroll/Leibniz-HKI

Meanwhile, BTZ-043 is to be further optimized, especially with regard to the pharmacokinetic properties of the active compound. The Leibniz-HKI thus remains an important player in the global fight against tuberculosis. A current study by researchers from the Transfer Group Anti-Infectives, published in Nature Communications Chemistry, investigates how targeted chemical modifications of BTZ influence its properties and how the substance is metabolized. This gives the researchers at the Leibniz-HKI new insights into how they can design and further develop new BTZ derivatives in the future.

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Original publication

Keiff F, Bernal FA, Joch M, Jacques dit Lapierre TJW, Li Y, Liebing P, Dahse HM, Vilotijevic I, Kloss F (2024) Modulation of the Meisenheimer complex metabolism of nitro-benzothiazinones by targeted C-6 substitution. Commun Chem, https://doi.org/10.1038/s42004-024-01235-x.