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A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody MK-1654 in healthy Japanese adults.

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اقرأ على الانترنت اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • المصدر:
      Publisher: WileyBlackwell Pub Country of Publication: United States NLM ID: 101474067 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1752-8062 (Electronic) Linking ISSN: 17528054 NLM ISO Abbreviation: Clin Transl Sci Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Malden, MA : WileyBlackwell Pub., 2008-
    • الموضوع:
      Respiratory Syncytial Virus Infections*/drug therapy ; Respiratory Syncytial Virus Infections*/prevention & control ; Respiratory Syncytial Virus, Human*; Adult ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal, Humanized ; Humans ; Infant ; Japan
    • نبذة مختصرة :
      Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among all infants worldwide and remains a significant cause of morbidity and mortality. To address this unmet medical need, MK-1654, a half-life extended RSV neutralizing monoclonal antibody, is in clinical development for the prevention of RSV disease in infants. This was a phase I, randomized, placebo-controlled, single-site, double-blind trial of MK-1654 in 44 healthy Japanese adults. The safety, tolerability, pharmacokinetics, antidrug antibodies (ADAs), and serum neutralizing antibody (SNA) titers against RSV were evaluated for 1 year after a single intramuscular (i.m.) or intravenous (i.v.) dose of MK-1654 or placebo in five groups (100 mg i.m., 300 mg i.m., 300 mg i.v., 1000 mg i.v., or placebo). MK-1654 was generally well-tolerated in Japanese adults. There were no serious drug-related adverse events (AEs) reported in any MK-1654 recipient and no discontinuations due to any AEs in the study. The half-life of MK-1654 ranged from 76 to 91 days across dosing groups. Estimated bioavailability was 86% for 100 mg i.m. and 77% for 300 mg i.m. One participant out of 33 (3.0%) developed detectable ADA with no apparent associated AEs. The RSV SNA titers increased in a dose-dependent manner among participants who received MK-1654. These data support the development of MK-1654 for use in Japanese infants.
      (© 2022 Merck Sharp & Dohme LLC. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
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    • الرقم المعرف:
      0 (Antibodies, Monoclonal)
      0 (Antibodies, Monoclonal, Humanized)
    • الموضوع:
      Date Created: 20220504 Date Completed: 20220718 Latest Revision: 20221014
    • الموضوع:
      20221213
    • الرقم المعرف:
      PMC9283748
    • الرقم المعرف:
      10.1111/cts.13290
    • الرقم المعرف:
      35506164