Replacing serum with dried blood microsampling for pharmacokinetics, viral neutralisation and immunogenicity bioanalysis supporting future paediatric development of RSM01, a candidate respiratory syncytial virus neutralising monoclonal antibody

Abstract

Background: Virus neutralising antibodies in serum are considered key correlates of protection for vaccines and monoclonal antibodies against respiratory syncytial virus (RSV). RSM01 is a novel, highly-potent, half-life-extended and fully-human monoclonal antibody candidate targeting the RSV prefusion F protein. Currently in Phase 1 development, RSM01 is primarily being developed to potentially provide an effective and affordable RSV prevention strategy in low- and middle-income countries. To evaluate the ability of dried blood collection to generate data sets and conclusions comparable to serum collection, we compared pharmacokinetics (PK) of RSM01, immunogenicity, and virus neutralisation for dried capillary blood samples with serum samples. Methods: RSM01 PK, anti-drug antibodies (ADA), and RSV-neutralising antibodies from the Phase 1 trial were analyzed and compared between matched serum and dried blood samples. Deming regression analysis was performed using baseline-corrected values to evaluate correlation between measurements in liquid serum versus dried blood. Results: The analysis showed good correlation (R2 > 0.95) between individual RSM01 concentrations measured in both serum and capillary blood. Analysis of RSM01 PK parameters in capillary blood yielded equivalent conclusions as from serum. A strong correlation (R2 > 0.95) was observed between RSV neutralising activity measured in both serum and capillary blood. In addition, RSV neutralising activity was correlated with RSM01 concentrations in both serum and capillary blood data sets. For ADA, individual sample results had 96% agreement (290/302) and overall participant ADA status had 93% agreement (52/56). Conclusions: Both RSM01 concentrations and RSV neutralising activity showed a strong correlation between the serum and blood measurements. ADA measurements also had an agreement of > 90% for individual samples and overall participant status. Our results demonstrate that dried blood is a suitable specimen type for collection and evaluation in the RSM01 clinical development program and shows promise as a useful approach to reduce patient burden in clinical trials, particularly for infants in low- and middle-income countries. Trial Registration: Clinicaltrials.gov NCT05118386 November 12, 2021.