This presentation will provide an overview of patient-centric sampling application in Islatravir (ISL) clinical trials. ISL is under development for treatment and prevention of HIV-1 infection. Concentrations of the pharmacologically active anabolite, ISL triphosphate (ISL-TP), are measured in PBMCs. However, PBMC collection involves a complex isolation and stabilization procedure limiting its applicability in late-phase trials. To address this challenge, microsampling of venous and capillary blood using VAMS and Tasso-M20 were explored for in-clinic and at-home settings. Novel methodologies to measure total ISL in dried blood were developed, representing circulating ISL and intracellular ISL-TP levels. Bioanalytical challenges associated with assay sensitivity, analyte stability and device material impact were addressed, and fit-for-purpose validation was conducted in light of regulatory guidance. Correlation analysis for clinical PK data obtained with traditional PBMC sampling versus microsampling was conducted to assess proof-of-concept for using total ISL in dried blood as surrogate read-out for ISL-TP in PBMCs.
Learning Objectives:
Upon completion, participant will learn an application of microsampling to address the unique needs of ISL trials related to acquiring intracellular ISL-TP PK with reduced patient burden and simplified collection.
Upon completion, participant will learn the approaches to address bioanalytical challenges for VAMS and Tasso-M20 dried blood method development, assay validation and sample analysis in a regulated bioanalytical environment.
Upon completion, participant will develop an understanding of VAMS and Tasso-M20 technologies for in-clinic and at-home PK sampling and considerations for implementation in clinical trials.
