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Conference Paper: Antiviral activity, pharmacokinetics and safety of the second-generation hepatitis B core inhibitor ABI-H2158 in Phase 1b study of patients with HBeAg-positive chronic hepatitis B infection

TitleAntiviral activity, pharmacokinetics and safety of the second-generation hepatitis B core inhibitor ABI-H2158 in Phase 1b study of patients with HBeAg-positive chronic hepatitis B infection
Authors
Issue Date2020
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
Digital International Liver Congress (Digital ILC 2020), 27-29 August 2020. In Journal of Hepatology, 2020, v. 73 n. Suppl. 1, p. S125 How to Cite?
AbstractBackground and aims: The HBV core protein plays an integral role in multiple steps of the HBV lifecycle. ABI-H2158 is a second-generation HBV core inhibitor in development for the treatment of chronic hepatitis B infection. Here we report the antiviral activity, pharmacokinetics (PK) and safety from a Phase 1b study in which patients (pts) were treated with ABI-H2158. Method: In each cohort, 9 pts (7 active, 2 placebo [Pbo]) were randomized in a blinded manner to receive either ABI-H2158 100, 300 or 500 mg or Pbo once daily for 14 days. Eligible pts were males or females aged ≥18 and ≤65 years, HBV treatment naive, HBeAg positive with HBV DNA ≥2 × 105 IU/mL and Metavir F0-F2. HBV DNA, pgRNA, HBeAg, HBsAg and HBcrAg were measured on Days 1, 8 and 15. PK was assessed on Days 1 and 14. Safety was evaluated by treatment-emergent adverse events (AEs) and laboratory parameters. Results: Across the cohorts, the mean (range) age of pts was 36 (19– 51) years, with the majority being male (59%), Asian (96%) and HBV genotype C (59%). At baseline, the mean (range) HBV DNA was 8.0 log10 (4.7–9.1) IU/mL, pgRNA was 6.8 log10 (5.2–7.9) U/mL and ALT was 40 (14–124) U/L. Change in HBV DNA and pgRNA from baseline to Day 15 and PK data are shown in the Table 1. AEs were reported for 38% (8/21) of pts receiving ABI-H2158 and 50% (3/6) receiving PBO. The majority of AEs were Grade 1; none were Grade 3 or 4, serious or led to treatment discontinuation. Headache was the only AE reported by more than 1 pt receiving ABI-H2158 (2 pts). Graded laboratory abnormalities were observed in 71% (15/21) of pts receiving ABI-H2158 and 50% (3/6) receiving Pbo, the majority of which were Grade 1. Transient increases in ALT were observed in 24% (5/21) of pts receiving ABI-H2158 (all Grade 1) and in 33% (2/6) receiving Pbo (1 Grade 1; 1 Grade 3). Conclusion: Results from this Phase 1b study demonstrate that ABIH2158 has potent antiviral activity and a favourable safety profile when administered once daily for 14 days supporting further evaluation in combination with nucleos(t)ide analogues in Phase 2.
DescriptionPoster presentation - Late Breaker: Posters - no. LBP05
Persistent Identifierhttp://hdl.handle.net/10722/289891
ISSN
2019 Impact Factor: 20.582
2015 SCImago Journal Rankings: 4.570

 

DC FieldValueLanguage
dc.contributor.authorAgarwal, K-
dc.contributor.authorNiu, J-
dc.contributor.authorDing, Y-
dc.contributor.authorGane, E-
dc.contributor.authorNguyen, T-
dc.contributor.authorAlves, K-
dc.contributor.authorEvanchick, M-
dc.contributor.authorZayed, H-
dc.contributor.authorHuang, Q-
dc.contributor.authorKnox, S-
dc.contributor.authorStamm, L-
dc.contributor.authorColonno, R-
dc.contributor.authorHassanein, T-
dc.contributor.authorKim, DJ-
dc.contributor.authorLim, YS-
dc.contributor.authorYuen, RMF-
dc.date.accessioned2020-10-22T08:18:57Z-
dc.date.available2020-10-22T08:18:57Z-
dc.date.issued2020-
dc.identifier.citationDigital International Liver Congress (Digital ILC 2020), 27-29 August 2020. In Journal of Hepatology, 2020, v. 73 n. Suppl. 1, p. S125-
dc.identifier.issn0168-8278-
dc.identifier.urihttp://hdl.handle.net/10722/289891-
dc.descriptionPoster presentation - Late Breaker: Posters - no. LBP05-
dc.description.abstractBackground and aims: The HBV core protein plays an integral role in multiple steps of the HBV lifecycle. ABI-H2158 is a second-generation HBV core inhibitor in development for the treatment of chronic hepatitis B infection. Here we report the antiviral activity, pharmacokinetics (PK) and safety from a Phase 1b study in which patients (pts) were treated with ABI-H2158. Method: In each cohort, 9 pts (7 active, 2 placebo [Pbo]) were randomized in a blinded manner to receive either ABI-H2158 100, 300 or 500 mg or Pbo once daily for 14 days. Eligible pts were males or females aged ≥18 and ≤65 years, HBV treatment naive, HBeAg positive with HBV DNA ≥2 × 105 IU/mL and Metavir F0-F2. HBV DNA, pgRNA, HBeAg, HBsAg and HBcrAg were measured on Days 1, 8 and 15. PK was assessed on Days 1 and 14. Safety was evaluated by treatment-emergent adverse events (AEs) and laboratory parameters. Results: Across the cohorts, the mean (range) age of pts was 36 (19– 51) years, with the majority being male (59%), Asian (96%) and HBV genotype C (59%). At baseline, the mean (range) HBV DNA was 8.0 log10 (4.7–9.1) IU/mL, pgRNA was 6.8 log10 (5.2–7.9) U/mL and ALT was 40 (14–124) U/L. Change in HBV DNA and pgRNA from baseline to Day 15 and PK data are shown in the Table 1. AEs were reported for 38% (8/21) of pts receiving ABI-H2158 and 50% (3/6) receiving PBO. The majority of AEs were Grade 1; none were Grade 3 or 4, serious or led to treatment discontinuation. Headache was the only AE reported by more than 1 pt receiving ABI-H2158 (2 pts). Graded laboratory abnormalities were observed in 71% (15/21) of pts receiving ABI-H2158 and 50% (3/6) receiving Pbo, the majority of which were Grade 1. Transient increases in ALT were observed in 24% (5/21) of pts receiving ABI-H2158 (all Grade 1) and in 33% (2/6) receiving Pbo (1 Grade 1; 1 Grade 3). Conclusion: Results from this Phase 1b study demonstrate that ABIH2158 has potent antiviral activity and a favourable safety profile when administered once daily for 14 days supporting further evaluation in combination with nucleos(t)ide analogues in Phase 2.-
dc.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep-
dc.relation.ispartofJournal of Hepatology-
dc.relation.ispartofDigital International Liver Congress (Digital ILC 2020)-
dc.titleAntiviral activity, pharmacokinetics and safety of the second-generation hepatitis B core inhibitor ABI-H2158 in Phase 1b study of patients with HBeAg-positive chronic hepatitis B infection-
dc.typeConference_Paper-
dc.identifier.emailYuen, RMF: mfyuen@hku.hk-
dc.identifier.authorityYuen, RMF=rp00479-
dc.description.natureabstract-
dc.identifier.doi10.1016/S0168-8278(20)30767-4-
dc.identifier.hkuros315872-
dc.identifier.volume73-
dc.identifier.issueSuppl. 1-
dc.identifier.spageS125-
dc.identifier.epageS125-
dc.publisher.placeNetherlands-

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