Efficacy and Safety of Treatment with an Anti-M2e Monoclonal Antibody in Experimental Human InfluenzaOctober 19, 2014 2:35 pm
Journal of Infectious Diseases, 3 October 2014
Background. The efficacy of TCN-032, a human mAb 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 single dose of 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. While the primary objective of reducing the proportion of subjects developing any Grade 2 or greater influenza symptom, or pyrexia, was not achieved, TCN-032-treated subjects showed 35% reduction (p=0.047) in median total symptom AUC (Days 1-7) and 2.2 log reduction in median viral load AUC (Days 2-7) by qPCR (p=0.095) compared to placebo subjects. TCN-032 was safe and well tolerated with no additional safety signals following administration of oseltamivir. Serum cytokine levels (IFN-γ, TNF-α, IL-8, IL-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 support 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.
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