{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T02:57:22Z","timestamp":1780541842358,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T00:00:00Z","timestamp":1595203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008897","name":"Janssen Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Four weeks of once\u2010daily oral JNJ\u201056136379 (JNJ\u20106379; 25, 75, 150 or 250\u00a0mg), a class\u2010N capsid assembly modulator (CAM\u2010N), was well tolerated with potent antiviral activity in treatment\u2010na\u00efve, chronic hepatitis B e antigen\u2013positive and hepatitis B e antigen\u2013negative patients (NCT02662712). Hepatitis B virus (HBV) genome sequence analysis, using HBV DNA next\u2010generation sequence technology, was performed, and impact of substitutions on efficacy was assessed. Analyses focused on HBV core protein amino acid positions associated with JNJ\u20106379 and\/or other CAMs in vitro resistance, and those within the CAM\u2010binding pocket. 31\/57 patients had\u00a0\u2265\u00a01 polymorphism at any of the core amino acid positions of interest, most frequently at positions 38 (32%), 105 (23%) and 109 (14%). None of these polymorphisms are known to reduce JNJ\u20106379 in vitro activity (fold change [FC] in 50% effective concentration &lt;3.0). Two JNJ\u20106379\u2010treated patients carried a Y118F baseline core polymorphism known to reduce JNJ\u20106379 activity in vitro (FC\u00a0=\u00a06.6) and had HBV DNA declines of 2.77 (75\u00a0mg) and 2.19 log<jats:sub>10<\/jats:sub> IU\/mL (150\u00a0mg) at the end of treatment. One 75\u00a0mg JNJ\u20106379\u2010treated patient had an emerging T109S substitution (FC\u00a0=\u00a01.8; HBV DNA decline 3.18 log<jats:sub>10<\/jats:sub> IU\/mL). A 25\u00a0mg JNJ\u20106379\u2010treated patient had on\u2010treatment enrichment of Y118F variant (HBV DNA decline 2.13 log<jats:sub>10<\/jats:sub> IU\/mL). In conclusion, baseline polymorphisms and enrichment of substitutions reducing JNJ\u20106379 in vitro activity were rare, with no consistent impact on virological response during a 4\u2010week phase 1b study. Emergence of resistance to longer treatments of JNJ\u20106379 will be evaluated in phase 2 studies.<\/jats:p>","DOI":"10.1111\/jvh.13351","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T16:50:35Z","timestamp":1593017435000},"page":"1127-1137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Virology analysis of chronic hepatitis B virus\u2013infected patients treated for 28 days with JNJ\u201056136379 monotherapy"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8627-400X","authenticated-orcid":false,"given":"Thierry","family":"Verbinnen","sequence":"first","affiliation":[{"name":"Janssen Research &amp; Development Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moana","family":"Hodari","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"Talloen","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Martin","family":"Berke","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Blue","sequence":"additional","affiliation":[{"name":"Janssen Biopharma Inc South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeysen","family":"Yogaratnam","sequence":"additional","affiliation":[{"name":"Janssen Biopharma Inc South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris","family":"Vandenbossche","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umesh","family":"Shukla","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceuticals Research &amp; Development Titusville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"De Meyer","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Lenz","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29800"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00436-3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14155"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01360-08"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02439-19"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00560-17"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00680-17"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-019-01017-1"},{"issue":"0016","key":"e_1_2_9_11_1","first-page":"30519","article-title":"JNJ\u201056136379, an HBV capsid assembly modulator, is well\u2010tolerated and has antiviral activity in a phase 1 study of patients with chronic infection","volume":"25","author":"Zoulim F","year":"2020","journal-title":"Gastroenterology"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa179"},{"key":"e_1_2_9_13_1","unstructured":"FDA.Submitting next generation sequencing data to the Division of Antiviral Products Guidance for Industry Technical Specifications Document Center for Drug Evaluation and Research July 2019. Available at: https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/submitting\u2010next\u2010generation\u2010sequencing\u2010data\u2010division\u2010antiviral\u2010products\u2010guidance\u2010industry\u2010technical last accessed 4 March 2020."},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2013.06.013"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00879"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00933-06"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1513803112"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(18)30251-4"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.08.063"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2006.00813.x"},{"key":"e_1_2_9_21_1","unstructured":"YuenMF BerlibaE SukeepaisarnjaroenW et al.Pharmacokinetics and antiviral activity of the capsid inhibitor AB\u2010506 in healthy subjects and chronic hepatitis B subjects. AASLD 2019 late breaking abstract LP7 available at https:\/\/www.aasld.org\/sites\/default\/files\/2019\u201010\/2019\u2010TLM\u2010LateBreakingAbstracts\u2010v2.pdf. last accessed 4 March 2020."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30346-2"},{"issue":"1","key":"e_1_2_9_23_1","first-page":"429a","article-title":"Analysis of factors influencing the efficacy and safety of GLS4 treatment in patients with chronic hepatitis B","volume":"70","author":"Zhang H","year":"2019","journal-title":"Hepatology"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.10.035"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1022"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.10.033"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn175"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.09.033"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0618-8278(19)30489-X"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-018-1502-y"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00556-10"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01444-15"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01734-18"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00082-18"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.13351","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13351","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvh.13351","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13351","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T13:07:53Z","timestamp":1693919273000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.13351"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,20]]},"references-count":33,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1111\/jvh.13351"],"URL":"https:\/\/doi.org\/10.1111\/jvh.13351","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,20]]},"assertion":[{"value":"2020-03-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}