Scientific paper 110 – Efficacy and Safety of Treatment With an Anti-M2e Monoclonal Antibody in Experimental Human Influenza

November 8, 2016 8:48 am

Authors – Eleanor L. Ramos,1,a Jennifer L. Mitcham,1,a Teri D. Koller,1,a Aurelio Bonavia,1,a Dale W. Usner,2 Ganesh Balaratnam,3 Paul Fredlund,1 and Kristine M. Swiderek1

published in Journal of Infectious Diseases (JID), 2015; 211:1038-44

1. Theraclone Sciences, Seattle, Washington;2. Statistics and Data Corporation, Tempe, Arizona;3. hVIVO plc formerly Retroscreen Virology Ltd, London, United Kingdom

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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 ≥2 influenza 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 benefit in 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.

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