Tuberculosis (TB) is a leading causes of morbidity and mortality worldwide.
It has historically been the most common infectious cause of death globally, surpassed only recently (and presumably temporarily) by the ongoing Covid-19 pandemic.
Current TB treatments are long, complex and often poorly tolerated; moreover, cases of the drug-resistant (rifampicin-resistant (RIF-R)) form of TB magnify this global health threat.
The WHO estimates that only 54% of patients who began RIF-R TB treatment in 2016 were cured.
In addition to these well-recognized shortcomings, current TB treatments, particularly those for RIF-R TB, leave a majority of cured patients with permanent, clinically significant lung impairment and radiographic evidence of bronchiectasis and fibrosis.
The EU-funded DRTB-HDT project will determine if two adjunctive host-directed therapies can prevent the poor outcomes of treatment in cases of RIF-R TB. Patients with RIF-R TB and other risk factors for poor outcome will participate in a randomised, controlled, three-armed multicentre trial.
All patients will receive standard multidrug TB therapy; and in the experimental arms they will additionally receive either CC-11050 or metformin.
These selected drug candidates represent two complementary host-directed therapy strategies: reducing inflammation or inducing host cell anti-microbial activity, respectively.
Our clinical sites are based in Germany, Romania, Moldova, Georgia, Mozambique and South Africa.
If successful, this ground-breaking project will increase Europe’s capacity to control RIF-R-TB by developing new treatments that increase the likelihood of cure and reduce the risk of life-long disability.
This project evaluates two adjunctive host-directed therapies in patients with rifampin-resistant tuberculosis (RIF-R-TB) in a phase 2 clinical trial. RIF-R-TB patients are at increased risk of death, treatment failure, and impaired post-TB lung function.
The trial’s two experimental arms add either CC-11050 (a type 4 phosphodiesterase inhibitor that reduces inflammation by increasing cellular levels of cyclic AMP) or metformin (an AMPK activator used to treat diabetes mellitus that alters cellular metabolism) to standard RIF-R-TB treatment.
A control arm receives standard RIF-R-TB treatment alone. The experimental arms are each compared individually to the control arm. The study’s two co-primary endpoints examine lung function (FEV1, in a superiority comparison) and sputum culture conversion (the likelihood of sputum culture conversion expressed as a hazard ratio, in a non-inferiority comparison).
Tuberculosis (TB) is a leading causes of morbidity and mortality worldwide.
It has historically been the most common infectious cause of death globally, surpassed only recently (and presumably temporarily) by the ongoing Covid-19 pandemic.
Current TB treatments are long, complex and often poorly tolerated; moreover, cases of the drug-resistant (rifampicin-resistant (RIF-R)) form of TB magnify this global health threat.
The WHO estimates that only 54% of patients who began RIF-R TB treatment in 2016 were cured.
In addition to these well-recognized shortcomings, current TB treatments, particularly those for RIF-R TB, leave a majority of cured patients with permanent, clinically significant lung impairment and radiographic evidence of bronchiectasis and fibrosis.
The EU-funded DRTB-HDT project will determine if two adjunctive host-directed therapies can prevent the poor outcomes of treatment in cases of RIF-R TB. Patients with RIF-R TB and other risk factors for poor outcome will participate in a randomised, controlled, three-armed multicentre trial.
All patients will receive standard multidrug TB therapy; and in the experimental arms they will additionally receive either CC-11050 or metformin.
These selected drug candidates represent two complementary host-directed therapy strategies: reducing inflammation or inducing host cell anti-microbial activity, respectively.
Our clinical sites are based in Germany, Romania, Moldova, Georgia, Mozambique and South Africa.
If successful, this ground-breaking project will increase Europe’s capacity to control RIF-R-TB by developing new treatments that increase the likelihood of cure and reduce the risk of life-long disability.
This project evaluates two adjunctive host-directed therapies in patients with rifampin-resistant tuberculosis (RIF-R-TB) in a phase 2 clinical trial. RIF-R-TB patients are at increased risk of death, treatment failure, and impaired post-TB lung function.
The trial’s two experimental arms add either CC-11050 (a type 4 phosphodiesterase inhibitor that reduces inflammation by increasing cellular levels of cyclic AMP) or metformin (an AMPK activator used to treat diabetes mellitus that alters cellular metabolism) to standard RIF-R-TB treatment.
A control arm receives standard RIF-R-TB treatment alone. The experimental arms are each compared individually to the control arm. The study’s two co-primary endpoints examine lung function (FEV1, in a superiority comparison) and sputum culture conversion (the likelihood of sputum culture conversion expressed as a hazard ratio, in a non-inferiority comparison).
