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.
RCT Entities:
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, tumornecrosis 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: Jacqueline M McBride; Jeremy J Lim; Tracy Burgess; Rong Deng; Michael A Derby; Mauricio Maia; Priscilla Horn; Omer Siddiqui; Daniel Sheinson; Haiyin Chen-Harris; Elizabeth M Newton; Dimitri Fillos; Denise Nazzal; Carrie M Rosenberger; Maikke B Ohlson; Rob Lambkin-Williams; Hosnieh Fathi; Jeffrey M Harris; Jorge A Tavel Journal: Antimicrob Agents Chemother Date: 2017-10-24 Impact factor: 5.191
Authors: Jacqueline M McBride; Jeremy J Lim; Tracy Burgess; Rong Deng; Michael A Derby; Mauricio Maia; Priscilla Horn; Omer Siddiqui; Daniel Sheinson; Haiyin Chen-Harris; Elizabeth M Newton; Dimitri Fillos; Denise Nazzal; Carrie M Rosenberger; Maikke B Ohlson; Rob Lambkin-Williams; Hosnieh Fathi; Jeffrey M Harris; Jorge A Tavel Journal: Antimicrob Agents Chemother Date: 2017-12-21 Impact factor: 5.191
Authors: Usama Ashraf; Laura Tengo; Laurent Le Corre; Guillaume Fournier; Patricia Busca; Andrew A McCarthy; Marie-Anne Rameix-Welti; Christine Gravier-Pelletier; Rob W H Ruigrok; Yves Jacob; Pierre-Olivier Vidalain; Nicolas Pietrancosta; Thibaut Crépin; Nadia Naffakh Journal: Proc Natl Acad Sci U S A Date: 2019-05-10 Impact factor: 11.205