Tuberculosis (TB) today rivals HIV/AIDS as the leading cause of death from infectious diseases.
The number of TB patients has never been higher and the growing proportion of drug-resistant TB is threatening control strategies both in the developing and developed world, Eastern Europe being a particularly worrying point in case.
The anTBiotic consortium aims to fuel the long-term TB clinical pipeline while immediately offering new options to clinicians when confronted with multidrug-resistant (MDR)-TB.
More specifically, the proposed studies aim to:
a) Establish the proof of concept of anti-TB efficacy in humans of a pioneering, first-in-class, low-dose GSK oxaborole clinical drug candidate;
b) Identify a combination of β-lactam antibiotics suitable for the treatment of MDR TB orally or as a once daily intravenous or intramuscular application and
c) Through the use of β-lactams and in particular meropenem, explore personalized treatment with biomarker-guided duration.
The anti-TB activity in humans will be established in a two-week EBA clinical studies that combine established (CFU, TTP) and new clinical markers (biomarkers, PET/CT).
These datasets will help ascertain anti-TB efficacy in humans and generate confidence on their validity in longer-term drug combination trials. A variety of modelling approaches to predict optimal dosing will be used.
Finally, our recently achieved proof of concept for β-lactams as a novel class of anti-TB drugs has been confirmed and refined in additional studies and has led to the incorporation of a β-lactam to WHO guidelines for drug-resistant TB treatment. Building upon the good results in the PoC studies, we next want to compare therapy outcomes of MDR-TB patients (receiving β-lactam-containing treatment) with biomarker defined therapy durations vs. standard of care, aiming for individualized treatment shortening.