{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:35:33Z","timestamp":1774647333203,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T00:00:00Z","timestamp":1666396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>ATI\u20102173 is an active site polymerase inhibitor nucleotide in development as part of a potentially curative regimen for chronic hepatitis B virus (HBV) infection. This study evaluated the safety, tolerability, pharmacokinetics (PK) and antiviral activity of ATI\u20102173. This was a phase 1b, randomized, double\u2010blind, placebo\u2010controlled trial in treatment\u2010naive adults with chronic HBV infection conducted in the Republic of Moldova and Ukraine (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>: NCT04248426). Patients positive for hepatitis B surface antigen were randomized 6:2 to receive once\u2010daily oral doses of ATI\u20102173 10, 25, or 50\u2009mg (<jats:italic>n<\/jats:italic>\u00a0=\u00a06 per dose) or placebo (<jats:italic>n<\/jats:italic>\u00a0=\u00a07) for 28\u2009days, with off\u2010treatment monitoring for 24\u2009weeks. Endpoints included PK parameters of ATI\u20102173 and its metabolite clevudine, maximum reduction from baseline in HBV DNA, and safety and tolerability. Treatment\u2010emergent adverse events occurred in eight patients (47%) receiving ATI\u20102173 and five (71%) receiving placebo; headache was the most common (<jats:italic>n<\/jats:italic>\u00a0=\u00a04). ATI\u20102173 PK was generally dose proportional. Systemic clevudine exposure with ATI\u20102173 dosing was substantially reduced compared with historical values observed with clevudine administration. On Day 28, mean changes from baseline in HBV DNA were \u22122.72 to \u22122.78\u2009log<jats:sub>10<\/jats:sub>\u00a0IU\/ml with ATI\u20102173 and +0.17\u2009log<jats:sub>10<\/jats:sub>\u00a0IU\/ml with placebo. Off\u2010treatment sustained viral suppression and decreases in covalently closed circular DNA biomarkers were observed in most patients; one maintained undetectable HBV DNA at 24\u2009weeks off treatment. In this 28\u2010day monotherapy study, ATI\u20102173 demonstrated safety and antiviral activity, with sustained off\u2010treatment effects and substantially reduced systemic clevudine exposure. These results support evaluation of ATI\u20102173 with tenofovir disoproxil fumarate in phase 2 studies.<\/jats:p>","DOI":"10.1111\/jvh.13753","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T16:54:10Z","timestamp":1665075250000},"page":"19-28","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A randomized phase 1b trial of the active site polymerase inhibitor nucleotide <scp>ATI<\/scp>\u20102173 in patients with chronic hepatitis B virus infection"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1925-2921","authenticated-orcid":false,"given":"Katherine E.","family":"Squires","sequence":"first","affiliation":[{"name":"Antios Therapeutics  Doylestown Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Ogilvie","sequence":"additional","affiliation":[{"name":"Antios Therapeutics  Doylestown Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Jucov","sequence":"additional","affiliation":[{"name":"ARENSIA Exploratory Medicine Republican Clinical Hospital  Chisinau Moldova"},{"name":"Department of Infectious Diseases Nicolae Testemitanu State University of Medicine and Pharmacy  Chisinau Moldova"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Anastasiy","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nicolae Testemitanu State University of Medicine and Pharmacy  Chisinau Moldova"},{"name":"ARENSIA Exploratory Medicine  Kiev Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelli","family":"Ghicavii","sequence":"additional","affiliation":[{"name":"ARENSIA Exploratory Medicine Republican Clinical Hospital  Chisinau Moldova"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jade","family":"Huguet","sequence":"additional","affiliation":[{"name":"Altasciences, Montreal  Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebeca","family":"Melara","sequence":"additional","affiliation":[{"name":"Altasciences, Montreal  Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Constantineau","sequence":"additional","affiliation":[{"name":"Altasciences, Montreal  Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abel","family":"De La Rosa","sequence":"additional","affiliation":[{"name":"Antios Therapeutics  Doylestown Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas L.","family":"Mayers","sequence":"additional","affiliation":[{"name":"Antios Therapeutics  Doylestown Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,22]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Hepatitis B Foundation.Hepatitis B facts and figures. 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