Prospectively predicting BPaMZ phase IIb/III trial outcomes using a translational mouse-to-human platform.

ABSTRACT: Despite known treatments, tuberculosis (TB) remains the world's top infectious killer, highlighting the pressing need for new drug regimens. To prioritize the most efficacious drugs for clinical testing, we previously developed a PK-PD translational platform with bacterial dynamics that reliably predicted short-term monotherapy outcomes in Phase IIa trials from preclinical mouse studies. In this study, we extended our platform to include PK-PD models that account for drug-drug interactions in combination regimens and bacterial regrowth in our bacterial dynamics model to predict cure at the end of treatment and relapse 6 months post-treatment. The Phase III STAND trial testing a new regimen comprised of pretomanid (Pa), moxifloxacin (M), and pyrazinamide (Z) (PaMZ) was suspended after a sep

SUBMITTER: Goh JJN 

PROVIDER: S-EPMC11459968 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature