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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EACH-3102 is a second-generation hepatitis C virus (HCV) nonstructural 5A (NS5A) protein inhibitor with potent activity against HCV genotype (GT)-1 through GT-6. An ongoing phase 2 open-label study evaluated the safety and efficacy of 8 and 6 weeks of ACH-3102 plus sofosbuvir therapy in treatment-na\u00efve patients with chronic HCV GT-1 infection, as discussed in this article.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EViral Infections Liver Conditions\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHepatology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EViral Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHepatology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELiver Conditions\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHepatology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EACH-3102 is a second-generation hepatitis C virus (HCV) nonstructural 5A (NS5A) protein inhibitor with potent activity against HCV genotype (GT)-1 through GT-6 [Zhao et al. EASL. 2012; Yang et al. AASLD. 2011]. ACH-3102 retains activity against multiple HCV variants resistant to first-generation NS5A inhibitors [Nakamoto S et al. \u003Cem\u003EWorld J Gastroenterol\u003C\/em\u003E. 2014; Gao M. \u003Cem\u003ECurr Opin Virol\u003C\/em\u003E. 2013; Zhao et al. EASL. 2012; Yang et al. AASLD. 2011]. ACH-3422, an HCV nonstructural 5B (NS5B) uridine nucleotide polymerase inhibitor, is under development for use in combination with ACH-3102.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EEdward J. Gane, MD, Auckland Hospital, Auckland, New Zealand, presented interim results of an ongoing phase 2 open-label study of ACH-3102 plus sofosbuvir, which was used as a proxy for ACH-3422. Sofosbuvir is an HCV NS5B uridine nucleotide polymerase inhibitor that has been studied in multiple clinical trials in combination with NS5A inhibitors [Feeney ER and Chung RT. \u003Cem\u003EBMJ\u003C\/em\u003E. 2014]. The objective of this study was to evaluate the safety and efficacy of 8 and 6 weeks of ACH-3102 plus sofosbuvir therapy in treatment-na\u00efve patients with chronic HCV GT-1 infection.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003ETwo cohorts of patients were enrolled. In Cohort 1, patients were randomized to receive ACH-3102 plus sofosbuvir for 8 weeks (n = 12) or observation without treatment for 12 weeks (n = 6). Sustained viral response 4 (SVR4) results were obtained before proceeding with Cohort 2. Cohort 2 included the 6 observational patients from Cohort 1 plus 12 newly randomized patients. The 6 Cohort 1 observational patients were assigned to ACH-3102 plus sofosbuvir for 6 weeks. The additional 12 patients were randomized to ACH-3102 plus sofosbuvir for 6 weeks (n = 6) or observation for 10 weeks (n = 6).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe primary end point was SVR at 12 weeks after treatment ended (SVR12) in patients who received 8 or 6 weeks of ACH-3102 plus sofosbuvir. The secondary end points included SVR4, SVR8, rapid virologic response (RVR), end-of-treatment response (ETR), and adverse event (AE) rates.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EIn Cohort 1, all 12 patients treated with ACH-3102 plus sofosbuvir achieved HCV RNA levels \u0026lt; the lower limit of quantification (LLOQ) by week 3 and \u0026lt; the LLOQ target not detected (LLOQ\u003Csub\u003ETND\u003C\/sub\u003E) by week 5. Among patients who received 8 weeks of active treatment, 100% achieved ETR, SVR4, SVR8, and SVR12, and 83% achieved RVR. To date, 5 Cohort 2 patients who received active treatment have achieved ETR. Eight patients who completed 4 weeks of treatment have achieved HCV RNA \u0026lt; LLOQ.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003E\n         \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E shows the treatment-emergent AEs occurring in \u0026gt; 10% of Cohort 1 patients.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/15586\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/15586\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15586\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003ETreatment-Emergent Adverse Events Occurring in \u0026gt; 10% of Cohort 1 Patients Through End of Treatment +4 wk\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003ECombination therapy with ACH-3102 and sofosbuvir for 8 weeks achieved rapid sustained viral load declines with 100% SVR12. These results were observed in patients with high baseline viral loads, including 9 patients with a baseline viral load \u0026gt; 6 000 000 international units (IU)\/ mL, 7 of whom had \u0026gt; 7 log\u003Csub\u003E10\u003C\/sub\u003E IU\/mL. A rapid decline in viral load was also observed after 6 weeks of treatment. The combination treatment was well tolerated with no significant AEs, electrocardiogram findings, or laboratory abnormalities. These observations will inform future clinical trials using ACH-3102 plus ACH-3422 as an interferon- and ribavirin-free regimen for the treatment of chronic HCV infection.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/48\/9.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzoeuq\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzoeuq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}