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

TitleSafety and antiviral activity of the HCV entry inhibitor ITX5061 in treatment-naive HCV-infected adults: a randomized, double-blind, phase 1b study.
Publication TypeJournal Article
Year of Publication2014
AuthorsSulkowski MS, Kang M, Matining R, Wyles D, Johnson VA, Morse GD, Amorosa V, Bhattacharya D, Coughlin K, Wong-Staal F, Glesby MJ
Corporate AuthorsAIDS Clinical Trials Group A5277 Protocol Team
JournalJ Infect Dis
Volume209
Issue5
Pagination658-67
Date Published2014 Mar 1
ISSN1537-6613
KeywordsAntiviral Agents, Double-Blind Method, Female, Hepacivirus, Hepatitis C, Chronic, Humans, Male, Middle Aged, Phenylenediamines, Sulfonamides
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.

DOI10.1093/infdis/jit503
Alternate JournalJ. Infect. Dis.
PubMed ID24041792
PubMed Central IDPMC3923538
Grant List5-P30-AI-045008-15 / AI / NIAID NIH HHS / United States
5UM1-AI069484-07 / AI / NIAID NIH HHS / United States
5UM1AI069415-07 / AI / NIAID NIH HHS / United States
5UO1 AI069502 / AI / NIAID NIH HHS / United States
AI-069467-07 / AI / NIAID NIH HHS / United States
AI-069513 / AI / NIAID NIH HHS / United States
AI69432 / AI / NIAID NIH HHS / United States
AI69465 / AI / NIAID NIH HHS / United States
K24 AI078884 / AI / NIAID NIH HHS / United States
K24 DA034621 / DA / NIDA NIH HHS / United States
K24DA00432 / DA / NIDA NIH HHS / United States
NIH UL1RR025005 / RR / NCRR NIH HHS / United States
NIH/NIAID 7UM1AI068636 / / PHS HHS / United States
R01 DA016065 / DA / NIDA NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
U01AI069452 / AI / NIAID NIH HHS / United States
UAB CFAR P30AI27767-24 / AI / NIAID NIH HHS / United States
UL1 RR 025005 / RR / NCRR NIH HHS / United States
UL1 RR024160 / RR / NCRR NIH HHS / United States
UL1 TR000042 / TR / NCATS NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
UL1TR00165 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069419 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069511 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UMI AI069511 / AI / NIAID NIH HHS / United States