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Article: Safety, pharmacokinetics and antiviral activity of ABI-H2158, a hepatitis B virus core inhibitor: A randomized, placebo-controlled phase 1 study

TitleSafety, pharmacokinetics and antiviral activity of ABI-H2158, a hepatitis B virus core inhibitor: A randomized, placebo-controlled phase 1 study
Authors
Keywordsantiviral
core inhibitor
hepatitis B virus
pharmacokinetics
phase 1 study
Issue Date12-Jan-2023
PublisherWiley
Citation
Journal of Viral Hepatitis, 2023, v. 30, n. 3, p. 209-222 How to Cite?
AbstractTreatment for chronic hepatitis B virus infection (cHBV) is mostly indefinite, with new finite-duration therapies needed. We report safety, pharmacokinetics and antiviral activity of the investigational HBV core inhibitor ABI-H2158. This Phase 1a/b study (NCT03714152) had three parts: Part A, participants received a single ascending oral dose of ABI-H2158 (5-500 mg) or placebo; Part B, participants received multiple doses of ABI-H2158 300 mg once (QD) or twice (BID) daily or placebo, for 10 days; Part C, cHBV patients received ABI-H2158 (100, 300, or 500 mg QD or 300 mg BID) or placebo, for 14 days. Ninety-three participants enrolled. In Parts A/B, there were no serious adverse events (SAEs) or deaths, and all treatment-emergent AEs (TEAEs) were Grade 1. In Part C, two patients had Grade 3 TEAEs unrelated to ABI-H2158; there were no deaths, SAEs or Grade 4 TEAEs. In Part A, median time to maximum ABI-H2158 plasma concentration (T-max) and mean terminal elimination half-life (t(1/2)) were 1-4 and 9.8-20.7 h, and area under the plasma concentration-time curve increased dose proportionally. In Part B, Day 10 T-max was 2 h, mean t(1/2) was 15.5-18.4 h, and exposure accumulated 1.7- to 3.1-fold. In Part C, Day 14 T-max was 1 h, exposure accumulated 1.4- to 1.8-fold, and ABI-H2158 was associated with >2 log(10) declines in HBV nucleic acids. In conclusion, ABI-H2158 in cHBV patients following 14 days of dosing was well tolerated and demonstrated potent antiviral activity. Safety and pharmacokinetics supported future QD dosing.
Persistent Identifierhttp://hdl.handle.net/10722/340812
ISSN
2023 Impact Factor: 2.5
2023 SCImago Journal Rankings: 1.078
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorAgarwal, K-
dc.contributor.authorXu, J-
dc.contributor.authorGane, EJ-
dc.contributor.authorNguyen, TT-
dc.contributor.authorDing, YH-
dc.contributor.authorKnox, SJ-
dc.contributor.authorAlves, K-
dc.contributor.authorEvanchik, M-
dc.contributor.authorZomorodi, K-
dc.contributor.authorMa, JL-
dc.contributor.authorYan, R-
dc.contributor.authorHuang, Q-
dc.contributor.authorColonno, R-
dc.contributor.authorStamm, LM-
dc.contributor.authorHassanein, TI-
dc.contributor.authorKim, DJ-
dc.contributor.authorLim, YS-
dc.contributor.authorYuen, MF-
dc.date.accessioned2024-03-11T10:47:27Z-
dc.date.available2024-03-11T10:47:27Z-
dc.date.issued2023-01-12-
dc.identifier.citationJournal of Viral Hepatitis, 2023, v. 30, n. 3, p. 209-222-
dc.identifier.issn1352-0504-
dc.identifier.urihttp://hdl.handle.net/10722/340812-
dc.description.abstractTreatment for chronic hepatitis B virus infection (cHBV) is mostly indefinite, with new finite-duration therapies needed. We report safety, pharmacokinetics and antiviral activity of the investigational HBV core inhibitor ABI-H2158. This Phase 1a/b study (NCT03714152) had three parts: Part A, participants received a single ascending oral dose of ABI-H2158 (5-500 mg) or placebo; Part B, participants received multiple doses of ABI-H2158 300 mg once (QD) or twice (BID) daily or placebo, for 10 days; Part C, cHBV patients received ABI-H2158 (100, 300, or 500 mg QD or 300 mg BID) or placebo, for 14 days. Ninety-three participants enrolled. In Parts A/B, there were no serious adverse events (SAEs) or deaths, and all treatment-emergent AEs (TEAEs) were Grade 1. In Part C, two patients had Grade 3 TEAEs unrelated to ABI-H2158; there were no deaths, SAEs or Grade 4 TEAEs. In Part A, median time to maximum ABI-H2158 plasma concentration (T-max) and mean terminal elimination half-life (t(1/2)) were 1-4 and 9.8-20.7 h, and area under the plasma concentration-time curve increased dose proportionally. In Part B, Day 10 T-max was 2 h, mean t(1/2) was 15.5-18.4 h, and exposure accumulated 1.7- to 3.1-fold. In Part C, Day 14 T-max was 1 h, exposure accumulated 1.4- to 1.8-fold, and ABI-H2158 was associated with >2 log(10) declines in HBV nucleic acids. In conclusion, ABI-H2158 in cHBV patients following 14 days of dosing was well tolerated and demonstrated potent antiviral activity. Safety and pharmacokinetics supported future QD dosing.-
dc.languageeng-
dc.publisherWiley-
dc.relation.ispartofJournal of Viral Hepatitis-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectantiviral-
dc.subjectcore inhibitor-
dc.subjecthepatitis B virus-
dc.subjectpharmacokinetics-
dc.subjectphase 1 study-
dc.titleSafety, pharmacokinetics and antiviral activity of ABI-H2158, a hepatitis B virus core inhibitor: A randomized, placebo-controlled phase 1 study-
dc.typeArticle-
dc.identifier.doi10.1111/jvh.13764-
dc.identifier.pmid36302125-
dc.identifier.scopuseid_2-s2.0-85146332209-
dc.identifier.volume30-
dc.identifier.issue3-
dc.identifier.spage209-
dc.identifier.epage222-
dc.identifier.eissn1365-2893-
dc.identifier.isiWOS:000912735700001-
dc.publisher.placeHOBOKEN-
dc.identifier.issnl1352-0504-

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