Clinical and virological responses to a broad-spectrum human monoclonal antibody in an influenza virus challenge study.

Autor: Sloan SE; Visterra, Inc., Waltham, MA, 02451, USA., Szretter KJ; Takeda Pharmaceuticals International, Inc., Cambridge, Massachusetts 02139, USA., Sundaresh B; Boston College, Chestnut Hill, MA, USA., Narayan KM; Visterra, Inc., Waltham, MA, 02451, USA., Smith PF; Certara, Parsippany, NJ, 07054, USA., Skurnik D; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Institut Necker-Enfants Malades, INSERM U1151, CNRS UMR, 8253, Paris, France; Université Paris Descartes, Paris, France; Service de Microbiologie, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France., Bedard S; Clin Ops Solutions, Medford, MA, USA., Trevejo JM; SmartPharm Therapeutics, Inc., Cambridge, MA, USA., Oldach D; Visterra, Inc., Waltham, MA, 02451, USA., Shriver Z; Visterra, Inc., Waltham, MA, 02451, USA. Electronic address: zshriver@visterrainc.com.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2020 Dec; Vol. 184, pp. 104763. Date of Electronic Publication: 2020 Mar 07.
DOI: 10.1016/j.antiviral.2020.104763
Abstrakt: Influenza A infections cause significant seasonal morbidity and mortality as well as periodic pandemic infections. Currently, no approved therapies exist for patients hospitalized with influenza. The efficacy of VIS410, a broadly neutralizing human immunoglobulin IgG1 monoclonal antibody engineered to bind to the stem region of group 1 and 2 influenza A hemagglutinins, was explored in experimental human influenza infection. Healthy volunteers were inoculated with influenza A/California/07/2009 (H1N1) and received a single dose of VIS410 or placebo 24 h later. Subjects were monitored for symptoms, viral shedding, and safety, including cytokine measurements. The primary efficacy endpoint was the area under the curve (AUC) of viral load (VL) in the VIS410 group versus placebo. VIS410 treatment was associated with a 76% reduction in median VL AUC as measured by qRT-PCR (p = 0.024). Similar VIS410 antiviral activity was observed by virus culture, with a 91% reduction in median VL AUC by TCID 50 (p = 0.019) compared to placebo-treated volunteers. Influenza symptoms were generally mild or moderate, with a trend toward faster resolution in VIS410-treated subjects. Treatment with VIS410 was generally safe, with an increase in gastrointestinal events that were largely mitigated by pre-treatment with oral diphenhydramine (50 mg) in combination with 600 mg of ibuprofen. Transient elevation of specific cytokines (IL-8 and TNFα) were associated with gastrointestinal adverse events. Treatment with VIS410 did not interfere with the endogenous immune response to influenza A. These data indicate that VIS410 may provide therapeutic benefit in influenza A infection. TRIAL REGISTRATION: ClinicaTtrials.gov Identification NCT02468115; https://clinicaltrials.gov/ct2/show/NCT02468115?term=NCT02468115&rank=1).
(Copyright © 2020 Visterra, Inc. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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