Safety and antiviral activity of the HCV entry inhibitor ITX5061 in treatment-naive HCV-infected adults: A randomized, double-blind, phase 1b study

Mark S. Sulkowski, Minhee Kang, Roy Matining, David Wyles, Victoria A. Johnson, Gene D. Morse, Valerianna Amorosa, Debika Bhattacharya, Kristine Coughlin, Flossie Wong-Staal, Marshall J. Glesby

Research output: Contribution to journalArticle

Abstract

Background. Hepatitis C virus (HCV) entry involves scavenger receptor B1 (SRB1). In vitro, SRB1 inhibition by ITX5061 impedes HCV replication.Methods. Multicenter study to assess safety/activity of ITX5061 in previously untreated, noncirrhotic, HCV genotype 1 infected adults. Design included sequential cohorts of 10 subjects with ITX5061 (n = 8) or placebo (n = 2) to escalate duration (3 to 14 to 28 days) or deescalate dose (150 to 75 to 25 mg) based on predefined criteria for safety and activity (≥4 of 8 subjects with HCV RNA decline ≥1 log10 IU/mL).Results. Thirty subjects enrolled in 3 cohorts: ITX5061 150 mg/day by mouth for 3 (A150), 14 (B150), and 28 (C150) days. Six subjects had grade ≥3 adverse events (one in placebo); none were treatment related. One of the 7 C150 subjects (14.3%, 95% confidence interval [CI],. 7%-55.4%) had ≥1 log10 IU/mL decline in HCV RNA (1.49 log10 IU/mL), whereas none of the 6 placebo, 8 A150 or 8 B150 subjects showed such decline.Conclusions. Oral ITX5061 150 mg/day for up to 28 days was safe and well tolerated. In the 28-day cohort, 1 of 7 subjects showed antiviral activity; however, predefined criteria for antiviral activity were not met at the doses and durations studied.

Original languageEnglish (US)
Pages (from-to)658-667
Number of pages10
JournalJournal of Infectious Diseases
Volume209
Issue number5
DOIs
StatePublished - Mar 2014

Keywords

  • HCV
  • SRB1
  • entry inhibitors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Sulkowski, M. S., Kang, M., Matining, R., Wyles, D., Johnson, V. A., Morse, G. D., Amorosa, V., Bhattacharya, D., Coughlin, K., Wong-Staal, F., & Glesby, M. J. (2014). Safety and antiviral activity of the HCV entry inhibitor ITX5061 in treatment-naive HCV-infected adults: A randomized, double-blind, phase 1b study. Journal of Infectious Diseases, 209(5), 658-667. https://doi.org/10.1093/infdis/jit503