title: Efficacy and safety of treatment with an anti-m2e monoclonal antibody in experimental human influenza.
abstract: 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.
authors.affiliation: Theraclone Sciences, Seattle, Washington.
authors.forename: Eleanor L
authors.initials: EL
authors.lastname: Ramos
authors.affiliation: Theraclone Sciences, Seattle, Washington.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Mitcham
authors.affiliation: Theraclone Sciences, Seattle, Washington.
authors.forename: Teri D
authors.initials: TD
authors.lastname: Koller
authors.affiliation: Theraclone Sciences, Seattle, Washington.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Bonavia
authors.affiliation: Statistics and Data Corporation, Tempe, Arizona.
authors.forename: Dale W
authors.initials: DW
authors.lastname: Usner
authors.affiliation: Retroscreen Virology Ltd, London, United Kingdom.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Balaratnam
authors.affiliation: Theraclone Sciences, Seattle, Washington.
authors.forename: Paul
authors.initials: P
authors.lastname: Fredlund
authors.affiliation: Theraclone Sciences, Seattle, Washington.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Swiderek
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000276:immunology*; D007251:Influenza, Human / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D053139:Oseltamivir / Q000008:administration & dosage*; D012189:Retrospective Studies; D016896:Treatment Outcome; D019562:Viral Load; D017201:Virus Shedding; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D007155:Immunologic Factors; D053139:Oseltamivir
keywords: TCN-032; anti-M2e antibody; influenza viral challenge