{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:04:54Z","timestamp":1770012294525,"version":"3.49.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T00:00:00Z","timestamp":1542585600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T00:00:00Z","timestamp":1542585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>This open\u2010label, phase IIa study assessed the safety, pharmacokinetics, and efficacy of direct\u2010acting antiviral agent (DAA) regimens in patients with chronic hepatitis C virus (HCV) infection. Multiple 6\u201012\u2010week oral regimens of 400\u2010800 mg once daily (QD) AL\u2010335 + 50\u00a0mg QD\/every other day odalasvir \u00b1 75\u2010150 mg QD simeprevir were evaluated in treatment\u2010na\u00efve, HCV genotype (GT)1\/3\u2010infected patients without cirrhosis. Safety\/pharmacokinetic parameters, HCV\u2010RNA, and sequencing data were assessed. Treatment regimens for later study cohorts were adjusted based on emerging data. In total, 112 patients were enrolled. Three serious treatment\u2010emergent adverse events occurred, one of which (a Mobitz type 1 second\u2010degree atrioventricular block [Wenckebach]) was possibly related to high odalasvir exposure and resulted in premature discontinuation of study drugs. No other clinically significant safety findings were identified. GT1\u2010infected patients receiving 3\u2010DAA for 6\u20108 weeks achieved 100% sustained virologic response 12 weeks and 24 weeks after the end of treatment (sustained virologic response [SVR12\/24]). GT1\u2010infected patients receiving 2\u2010DAA or GT3\u2010infected patients receiving 3\u2010DAA had SVR12\/24 less than 90%, whether treated for 8 weeks or 12 weeks. Virologic failure was associated with the emergence of generally persistent NS5A and\/or transient NS5B resistance\u2010associated substitutions in most patients. Pharmacokinetic characteristics of the three drugs were also elucidated. <jats:italic toggle=\"yes\">Conclusions:<\/jats:italic> In treatment\u2010na\u00efve subjects without cirrhosis, AL\u2010335 + odalasvir + simeprevir for 6\u20108 weeks was generally safe and highly efficacious against HCV GT1. However, inadequate efficacy was observed for the 2\u2010DAA regimen in GT1\u2010infected subjects and the 3\u2010DAA regimen in GT3\u2010infected subjects.<\/jats:p>","DOI":"10.1002\/hep.30126","type":"journal-article","created":{"date-parts":[[2018,8,6]],"date-time":"2018-08-06T22:16:08Z","timestamp":1533593768000},"page":"2145-2157","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":10,"title":["Short\u2010Duration AL\u2010335, Odalasvir, With or Without Simeprevir, in Patients With HCV GT1 or 3 Infection Without Cirrhosis"],"prefix":"10.1097","volume":"68","author":[{"given":"Edward J.","family":"Gane","sequence":"first","affiliation":[{"name":"Auckland Clinical Studies,Auckland,New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine A.","family":"Stedman","sequence":"additional","affiliation":[{"name":"Christchurch Hospital and University of Otago,Christchurch,New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Schwabe","sequence":"additional","affiliation":[{"name":"Auckland Clinical Studies,Auckland,New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leen","family":"Vijgen","sequence":"additional","affiliation":[{"name":"Janssen Research & Development,Janssen Pharmaceutica NV,Beerse,Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sushmita","family":"Chanda","sequence":"additional","affiliation":[{"name":"Alios BioPharma Inc. part of the Janssen Pharmaceutical Companies,South San Francisco,California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6857-2572","authenticated-orcid":false,"given":"Thomas N.","family":"Kakuda","sequence":"additional","affiliation":[{"name":"Alios BioPharma Inc. part of the Janssen Pharmaceutical Companies,South San Francisco,California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Fry","sequence":"additional","affiliation":[{"name":"Alios BioPharma Inc. part of the Janssen Pharmaceutical Companies,South San Francisco,California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence M.","family":"Blatt","sequence":"additional","affiliation":[{"name":"Alios BioPharma Inc. part of the Janssen Pharmaceutical Companies,South San Francisco,California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew W.","family":"McClure","sequence":"additional","affiliation":[{"name":"Alios BioPharma Inc. part of the Janssen Pharmaceutical Companies,South San 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