Efficacy and Safety of Treatment with an Anti-M2e Monoclonal Antibody in Experimental Human Influenza

Background. The efficacy of TCN-032, a human monoclonal antibody targeting a conserved epitope on M2e, was explored in experimental human influenza. Methods. Healthy volunteers were inoculated with influenza A/Wisconsin/67/2005 (H3N2) and received a single dose of the study drug, TCN-032, or placebo 24 hours later. Subjects were monitored for symptoms, viral shedding, and safety, including cytokine measurements. Oseltamivir was administered 7 days after inoculation. Results. Although the primary objective of reducing the proportion of subjects developing any grade ≥ 2i nfluenza symptom or pyrexia, was not achieved, TCN-032–treated subjects showed 35% reduction (P= .047) in median total symptom area under the curve (days 1–7) and 2.2 log reduction in median viral load area under the curve (days 2–7) by quantitative polymerase chain reaction (P= .09) compared with placebo-treated subjects. TCN-032 was safe and well tolerated with no additional safety signals after administration of oseltamivir. Serum cytokine levels (interferon γ, tumor necrosis factor α, and interleukin 8 and 10) were similar in both groups. Genotypic and phenotypic analyses showed no difference between virus derived from subjects after TCN-032 treatment and parental strain. Conclusions. These data indicate that TCN-032 may provide immediate immunity and therapeutic benefi ti n influenza A infection, with no apparent emergence of resistant virus. TCN-032 was safe with no evidence of immune exacerbation based on serum cytokine expression. Clinicaltrials.gov registry number. NCT01719874.