Human challenge studies in healthy volunteers: practical considerations and outcomes of influenza trials

Abstract

Event Abstract Back to Event Human challenge studies in healthy volunteers: practical considerations and outcomes of influenza trials Josué K. Mfopou1, Gaël Memoli1, Haiko Pillu1, Heidi De Swert1* and Patricia De Cock1 1 SGS Belgium NV, Clinical Pharmacology Unit Antwerpen, Belgium Background: Influenza challenge studies in healthy volunteers aim at disease modelling in strictly-regulated and controlled conditions, and testing novel antiviral/anti-inflammatory therapies. An optimal human model requires a virulent species with high infectivity, relevant symptoms without safety concerns, as well as optimal methods for virus preparation, inoculation, sample management and data analysis. We report our experience with influenza trials at our clinical site. Methods: Our challenge models included influenza A subtypes H1N1 and H3N2, inoculated (0.25 mL per nostril) with a pipette or a VaxINator device respectively. Immunity to influenza was assessed by hemagglunitation-inhibition (HAI) or microneutralisation (MNT) assays, and adventitious agents in the airways were screened using semi-quantitative PCR1. Influenza-like illness (ILI) was monitored twice daily using a 35-questions symptoms scorecard (SSC)2, qPCR and tissue culture. Results: Subjects’ selection strategy was crucial, with 29% (MNT) to 58% (HAI) volunteers being excluded for immunity to influenza and 12-13% for abnormal spirometry records. Inoculation with VaxINator device, which produces a spray of challenge agent in the airways, was much appreciated by the operational team. The SSC showed a dose-dependent ILI between 3 to 5 days post-inoculation, and this pattern correlated with viral shedding in the three dose groups (H3N2) or in the treated versus placebo groups (H1N1) as assessed by qPCR and viral culture. Conclusion: Human challenge studies are intensive processes requiring close monitoring and optimal techniques to deliver reliable data. Our influenza H1N1 and H3N2 challenge studies provided expected outcomes while following standardized methods. Another H3N2 interventional study is currently in recruitment phase.