(T1130-02-06) Using Tasso-M20 Microsampling Device to Support a Clinical PK Study

Purpose: Microsampling technologies have drawn significant interest in patient-centric clinical studies. Compared with the traditional venous blood sampling, the advantages include reduced patient burden allowing smaller sampling volume and less invasive collection procedure. Specifically, the Tasso-M20 micro-volumetric sampling device collects dried capillary blood and enables at-home collection which enhances patient comfort and reduces anxiety associated with blood draws. Additionally, the Tasso-M20 device supports decentralized healthcare models, making it easier to gather data across diverse populations and improve access to essential lab testing. The device is also significant for its potential to increase patient participation in monitoring their health, which is essential for chronic disease management and preventive care. This device was evaluated for pharmacokinetic (PK) sampling in a subset of clinical study for Com-A program. This approach involved for the first time the use of a novel M20 LBA method at the company to quantify Com-A in dried blood. The data was used for evaluating the correlation of Com-A concentrations obtained between dried capillary blood sampling and conventional serum PK sampling.

Methods: The ligand binding assay (LBA) assay format for quantitation of Com-A in dried human blood from Tasso-M20 employed an electrochemiluminescence (ECL) immunoassay on the MSD Sector S 600 platform. This method utilized 96-well streptavidin coated plate with biotinylated monoclonal antibody against Com-A as the capture reagent and sulfo-TAG labeled monoclonal antibody against Com-A as the detection reagent. The calibration range in 100% dried human blood was 3.13 to 200 ng/mL. Each M20 Tasso tip collects 17.5 μL of capillary blood. The Tasso-M20 tip of standards, QCs, and samples were detached from the devices and submerged into 350 μL of 1% BSA/PBST on a Protein LoBind deep well plate and agitated on Thermomixer C at 1200 rpm for 2 hours at Room temperature. The eluate of samples, standards, and quality controls were diluted by 2-fold with 1%BSA/PBST. The final minimum required dilution (MRD) was 1:40 (equivalent to 2.5% blood). The lower limit of quantitation (LLOQ) is 3.13 ng/mL. A 4PL (MARQUARDT,1/Y2) regression model was applied. Tasso-M20 dried blood samples were stored at controlled room temperature prior to analysis.

Results: An LBA method for the determination of Com-A concentrations in human dried blood collected by an M20 device using Meso-Scale Discovery (MSD) electrochemiluminescence (ECL) has been developed and validated for use in support of clinical PK studies. The results demonstrated the method is sensitive, selective, accurate, and reproducible. Storage stability at controlled room temperature was assessed to cover the duration from study sample collection until completion of sample analysis. Accelerated stability testing at 40°C/75%RH was also conducted to assess the impact of sample collection deviations at the clinical site. A total of 128 clinical M20 samples were analyzed. Incurred sample reanalysis (ISR) showed a passing rate of 93.3%, suggesting robust assay performance. Sample collection issues at the clinical site were encountered and may impact sample quality. The observed issues include 1) incomplete drying by failure to remove the film on the device; 2) blood under-fill or over-fill leading to inaccurate sampling volumes.

Conclusion: The M20 bioanalytical assay performed well with high precision and accuracy. However, sample collection deviations at the clinical site may cause analyte degradation and impact the correlation with traditional serum PK sampling. The experience gained from this study will help inform future application of Tasso M20 sampling.

Acknowledgements: Garrett Nieddu, Alex Becker, Iris Xie, Rana Ramdass


Figure 1. Com-A-013 Study Schematic


Table 1. Analytical Performance of Com-A Quality Control Samples in Human Dried Blood M20 (Study Com-A 013)


Figure 3. Tasso PK and serum PK concentration correlation difference. Period 1: Tasso sample collection deviations observed at clinical site. Period 2: Tasso sample collection issue corrected at clinical site