An Integrated Nonclinical and Clinical Risk Assessment of the Effects of Investigational ATRi Tuvusertib on QTc Interval in Patients With Solid Tumors

This publication highlights how pharmacometric modeling, supported by Certara, was used to inform dose selection for clazakizumab, an anti–IL-6 monoclonal antibody, in patients with end-stage kidney disease on dialysis. Leveraging data from a Phase 2 trial, Certara scientists developed population pharmacokinetic (popPK) and PK–PD models to characterize drug exposure and its impact on reducing inflammation, measured by hs-CRP. The analysis demonstrated that clazakizumab follows a two-compartment model with linear elimination and reduces hs-CRP through an indirect mechanism by inhibiting its production. Despite limited differentiation across dose levels due to strong responses, Certara’s modeling and simulation approach enabled robust evaluation of exposure–response relationships and supported selection of an optimal dosing regimen of 5 mg IV every 4 weeks for Phase 3 studies. This work underscores the critical role of Certara’s model-informed drug development expertise in enabling confident, data-driven decisions when traditional approaches are limited.