UCSF

Optimizing Clofazimine (CFZ) for TB in Children, Systems Model of TB Including Translation from EBA Study to Clinical Trial Efficacy

The Savic Lab is taking steps to optimize the use of clofazimine (CFZ) for TB treatment in children by delivering insights for CFZ pediatric dosing and improving pediatric studies. Although it has been marketed as an anti-leprosy drug since its discovery, clofazimine is one of the five core drugs used in a standardized, shorter MDR-TB treatment regimen – published as part of the 2016 WHO treatment guidelines in an effort to reduce treatment duration from 18 months to nine to 12 months. However, no CFZ PK studies have been done in children, and the CFZ dosing regimen has not yet been optimized for children with TB.

Unlike adult patients, children with TB do not develop cavitary disease. Therefore, the standard BALB/c mouse model, which does not include cavities, can be used to mimic the effects of TB in school-aged children for CFZ-regimen optimization. Our work aims to understand the exposure-response relationship of CFZ through the study of multiple CFZ doses in a BALB/c mouse model, to provide insights regarding pediatric CFZ-dosing and the improvement of pediatric studies through the translation of the PK/PD relationship seen in the BALB/c mouse model.