September 23, 2013

Safety and Antiviral Activity of the HCV Entry Inhibitor ITX5061 in Treatment-Naïve HCV- Infected Adults: A Randomized, Double-Blind, Phase 1b Study

J Infect Dis. (2013) doi: 10.1093/infdis/jit503 First published online: September 16, 2013

Mark S. Sulkowski1, Minhee Kang2, Roy Matining2, David Wyles3, Victoria A. Johnson4, Gene D. Morse5, Valerianna Amorosa6, Debika Bhattacharya7, Kristine Coughlin8, Flossie Wong-Staal9, Marshall J. Glesby10, for the AIDS Clinical Trials Group A5277 Protocol Team

+ Author Affiliations

To whom correspondence should be addressed: Mark S. Sulkowski, MD, 1830 Building, Room 445, 600 North Wolfe Street, Baltimore, Maryland 21287; Phone: 410 583-2736; Fax: 410 583-2654; Email:


Background. 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, non-cirrhotic, 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 de-escalate dose (150 to 75 to 25 mg) based on pre-defined criteria for safety and activity (≥4 of 8 subjects with HCV RNA decline≥1 log10 IU/mL).

Results. Thirty subjects enrolled in three 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 seven C150 subjects (14.3%, 95% CI 0.7%-55.4%) had≥1 log10 IU/mL decline in HCV RNA (1.49 log10 IU/mL) whereas none of the six placebo, eight A150 or eight 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.

Received June 30, 2013. Revision received August 15, 2013. Accepted August 27, 2013.


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