A Novel pan-TB Regimen Targeting Both Host and Microbe
Tuberculosis is a leading global cause of morbidity and mortality. Even if cured, most patients are left with permanent lung damage that impairs lung function and shortens long-term survival. These concerns are increased many-fold in rifampin-resistant (RIF-R) TB, in which cure is less likely, and long-term outcomes are more profoundly affected. This project will develop the first regimen meeting WHO criteria for a pan-TB indication, ie, without requiring knowledge of RIF susceptibility. The regimen will combine sutezolid (a linezolid analog with a superior therapeutic index and safety profile in phase 1 and 2 trials) with the approved anti-TB drugs bedaquiline and delamanid. This phase 2c trial will test sutezolid at 2 dose levels to optimize its efficacy and safety. It will also test whether the addition of N-acetylcysteine (NAC), a re-purposed host-directed WHO essential medicine, can protect the lung and liver against oxidative damage, preserve lung function, and accelerate the eradication of MTB infection by replenishing glutathione (GSH). Our modelling indicates this new regimen (SBDN) can be a highly effective intervention, preventing deaths due to treatment failure in patients with RIF-R-TB, and recovering years of life otherwise lost post-TB in all patients by preserving lung function. The project will be conducted by a consortium of public, non-profit, and private interests that bring unique knowledge, expertise, and capabilities.
Aurum is an independent non-profit institute dedicated to solving health problems of the poor through research and implementation. It is based in Johannesburg, South Africa. Aurum has overall responsibility for this project.
Ludwig Maximilian University of Munich is a German public research university. LMU is responsible for Data Management and Statistics, and will assist in spirometry training.
The Wits Health Consortium (Pty) Limited (WHC) is wholly-owned by the University of the Witwatersrand. Its Clinical HIV Research Unit will participate in clinical activities in this project.
The Instituto Nacional de Saúde (INS), Ministry of Health, Mozambique, is a public health research institution, focusing on epidemiological surveys and conduct of clinical trials. It will participate in clinical activities in this project.
The National Institute for Medical Research - Mbeya Medical Research Center is a leading institution conducting clinical trials in Africa in the areas of TB, HIV, and malaria. NIMR-MMRC will participate in clinical activities in this project.
Radboud University Medical Centre specializes in patient care, scientific research, teaching and training. Its Department of Pharmacy will perform PK analyses and PK/PD modeling for this project.
Stellenbosch University is amongst South Africa's leading tertiary research institutions. Its Division of Molecular Biology and Human Genetics will perform MTB whole genome sequencing for this project.
Sequella is a clinical-stage pharma company that develops new and better antibiotics to address drug resistant bacterial, fungal, and parasitic infections.
This project RIA2019AMR-2647 is part of the EDCTP2 programme of of the European Union.