{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:44:24Z","timestamp":1786977864653,"version":"build-2736575974"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>RO7062931 is an N\u2010acetylgalactosamine (GalNAc)\u2010conjugated single\u2010stranded locked nucleic acid oligonucleotide complementary to HBV RNA. GalNAc conjugation targets the liver through the asialoglycoprotein receptor (ASGPR). This two\u2010part phase\u00a01 study evaluated the safety, pharmacokinetics, and pharmacodynamics of RO7062931 in healthy volunteers and patients with chronic hepatitis\u00a0B (CHB) who were virologically suppressed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      Part\u00a01 was a single ascending dose study in healthy volunteers randomized to receive a single RO7062931 dose (0.1\u20104.0\u00a0mg\/kg), or placebo. Part\u00a02 was a multiple ascending dose study in patients with CHB randomized to receive RO7062931 at 0.5, 1.5, or 3.0\u00a0mg\/kg or placebo every month for a total of 2\u00a0doses (Part\u00a02a) or RO7062931 at 3.0\u00a0mg\/kg every 2\u00a0weeks, 3.0\u00a0mg\/kg every week (QW), or 4.0\u00a0mg\/kg QW or placebo for a total of 3\u20105\u00a0doses (Part\u00a02b). Sixty healthy volunteers and 59\u00a0patients received RO7062931 or placebo. The majority of adverse events (AEs) reported were mild in intensity. Common AEs included self\u2010limiting injection site reactions and influenza\u2010like illness. Supradose\u2010proportional increases in RO7062931 plasma exposure and urinary excretion occurred at doses \u22653.0\u00a0mg\/kg. In patients with CHB, RO7062931 resulted in dose\u2010dependent and time\u2010dependent reduction in HBsAg versus placebo. The greatest HBsAg declines from baseline were achieved with the 3.0\u00a0mg\/kg QW dose regimen (mean nadir ~0.5\u00a0log\n                      <jats:sub>10<\/jats:sub>\n                      \u00a0IU\/mL) independent of HBeAg status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RO7062931 is safe and well tolerated at doses up to 4.0\u00a0mg\/kg QW. Supradose\u2010proportional exposure at doses of 3.0\u20104.0\u00a0mg\/kg was indicative of partial saturation of the ASGPR\u2010mediated liver uptake system. Dose\u2010dependent declines in HBsAg demonstrated target engagement with RO7062931.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.31920","type":"journal-article","created":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T06:28:01Z","timestamp":1622010481000},"page":"1795-1808","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":40,"title":["Clinical Study of Single\u2010Stranded Oligonucleotide RO7062931 in Healthy Volunteers and Patients With Chronic Hepatitis B"],"prefix":"10.1097","volume":"74","author":[{"given":"Edward","family":"Gane","sequence":"first","affiliation":[{"name":"Auckland Clinical Studies,Auckland,New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man\u2010Fung","family":"Yuen","sequence":"additional","affiliation":[{"name":"Queen Mary Hospital,The University of Hong Kong,Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong 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