File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Conference Paper: Antiviral activity and safety of the hepatitis B core inhibitor ABI-H0731 administered with a nucleos(t)ide reverse transcriptase inhibitor in patients with HBeAg-positive chronic hepatitis B infection in a long-term extension study

TitleAntiviral activity and safety of the hepatitis B core inhibitor ABI-H0731 administered with a nucleos(t)ide reverse transcriptase inhibitor in patients with HBeAg-positive chronic hepatitis B infection in a long-term extension study
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. S140 How to Cite?
AbstractBackground and aims: ABI-H0731 (731) is a first-generation HBV core inhibitor in development for the treatment of chronic hepatitis B infection (CHB). In the Phase 2a studies 202 and 201, treatment naïve (TN) and virally suppressed (VS) HBeAg-positive patients (pts) with CHB were randomized 1:1 to 731 or placebo (Pbo) with NrtI in a blinded manner for 24 weeks. The combination of 731+NrtI was well tolerated and demonstrated faster and greater reductions in HBV DNA and pgRNA than NrtI alone. Following study completion, eligible pts entering an open-label extension study 211 received 731+NrtI for up to an additional 76 weeks. Here we report the updated data from study 211 through the current last reported observation. Method: For TN pts, HBV DNA was measured by COBAS TaqMan 2.0 (LLOQ = 20 IU/mL) and pgRNA by an in-house quantitative PCR assay (LLOQ = 135 U/mL). For VS pts, HBV DNA was measured by an inhouse semi-quantitative PCR assay (LLOD = 5 IU/mL) and pgRNA by an in-house semi-quantitative RT-PCR assay (LLOD = 5 IU/mL). For all pts, quantitative HBeAg and HBsAg were measured by Abbott Architect (LLOQ = 0.11 IU/mL and 0.05 IU/mL, respectively) and HBcrAg by Lumipulse G (LLOD = 1 kU/mL). Safety was assessed by adverse events (AEs) and laboratory parameters. Results: Of the 23 TN pts from study 202, median (range) treatment duration 57 (36–83) weeks, 21 pts have DNA declines to <100 IU/mL and 6 pts have pgRNA declines to <500 U/mL. Declines of ≥1 log or at 5% was upper respiratory tract infection (4 pts, 6%). Most laboratory abnormalities were Grade 1 or 2. Transient or intermittent Grade 3 elevations in ALT were observed in 2 pts (3%), both of whom continue on study drug. Conclusion: Results from the ongoing Phase 2a extension study demonstrate continued declines in HBV DNA, pgRNA and viral antigens in pts treated with 731+NrtI. 731 continues to exhibit a favorable safety and tolerability profile in pts treated for over 1 year. The data support the continued development of 731.
DescriptionPoster presentation - Late Breaker: Posters - no. LBP30
Persistent Identifierhttp://hdl.handle.net/10722/290213
ISSN
2019 Impact Factor: 20.582
2015 SCImago Journal Rankings: 4.570

 

DC FieldValueLanguage
dc.contributor.authorYuen, RMF-
dc.contributor.authorAgarwal, K-
dc.contributor.authorMa, X-
dc.contributor.authorNguyen, T-
dc.contributor.authorSchiff, ER-
dc.contributor.authorHann, HW-
dc.contributor.authorDieterich, D-
dc.contributor.authorNahass, R-
dc.contributor.authorPark, J-
dc.contributor.authorChan, S-
dc.contributor.authorHan, SH-
dc.contributor.authorGane, E-
dc.contributor.authorBennett, M-
dc.contributor.authorAlves, K-
dc.contributor.authorZayed, H-
dc.contributor.authorHuang, Q-
dc.contributor.authorColonno, R-
dc.contributor.authorKnox, S-
dc.contributor.authorStamm, L-
dc.contributor.authorBonacini, M-
dc.contributor.authorJacobson, I-
dc.contributor.authorAyoub, W-
dc.contributor.authorWeilert, F-
dc.contributor.authorRavendhran, N-
dc.contributor.authorRamji, A-
dc.contributor.authorKwo, P-
dc.contributor.authorElkhashab, M-
dc.contributor.authorHassanein, T-
dc.contributor.authorBae, H-
dc.contributor.authorLalezari, J-
dc.contributor.authorFung, S-
dc.contributor.authorSulkowski, M-
dc.date.accessioned2020-10-22T08:23:37Z-
dc.date.available2020-10-22T08:23:37Z-
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. S140-
dc.identifier.issn0168-8278-
dc.identifier.urihttp://hdl.handle.net/10722/290213-
dc.descriptionPoster presentation - Late Breaker: Posters - no. LBP30-
dc.description.abstractBackground and aims: ABI-H0731 (731) is a first-generation HBV core inhibitor in development for the treatment of chronic hepatitis B infection (CHB). In the Phase 2a studies 202 and 201, treatment naïve (TN) and virally suppressed (VS) HBeAg-positive patients (pts) with CHB were randomized 1:1 to 731 or placebo (Pbo) with NrtI in a blinded manner for 24 weeks. The combination of 731+NrtI was well tolerated and demonstrated faster and greater reductions in HBV DNA and pgRNA than NrtI alone. Following study completion, eligible pts entering an open-label extension study 211 received 731+NrtI for up to an additional 76 weeks. Here we report the updated data from study 211 through the current last reported observation. Method: For TN pts, HBV DNA was measured by COBAS TaqMan 2.0 (LLOQ = 20 IU/mL) and pgRNA by an in-house quantitative PCR assay (LLOQ = 135 U/mL). For VS pts, HBV DNA was measured by an inhouse semi-quantitative PCR assay (LLOD = 5 IU/mL) and pgRNA by an in-house semi-quantitative RT-PCR assay (LLOD = 5 IU/mL). For all pts, quantitative HBeAg and HBsAg were measured by Abbott Architect (LLOQ = 0.11 IU/mL and 0.05 IU/mL, respectively) and HBcrAg by Lumipulse G (LLOD = 1 kU/mL). Safety was assessed by adverse events (AEs) and laboratory parameters. Results: Of the 23 TN pts from study 202, median (range) treatment duration 57 (36–83) weeks, 21 pts have DNA declines to <100 IU/mL and 6 pts have pgRNA declines to <500 U/mL. Declines of ≥1 log or at <LLOQ in HBeAg, HBcrAg and HBsAg have been observed in 6, 8 and 3 pts, respectively. Of the 43 VS pts from study 201, median (range) treatment duration 58 (30–81) weeks, 34 and 21 pts have now achieved DNA and pgRNA <5 IU/mL, respectively. In addition, 29 pts have HBeAg <5 IU/mL, 27 pts have HBcrAg <500 kU/mL and 4 pts have HBsAg <1000 IU/mL. During the first 24 weeks of study 211, AEs were reported by 47% (31/66) pts, most of which were Grade 1 or 2. There were no SAEs or AEs leading to study drug discontinuation. The only AE reported by >5% was upper respiratory tract infection (4 pts, 6%). Most laboratory abnormalities were Grade 1 or 2. Transient or intermittent Grade 3 elevations in ALT were observed in 2 pts (3%), both of whom continue on study drug. Conclusion: Results from the ongoing Phase 2a extension study demonstrate continued declines in HBV DNA, pgRNA and viral antigens in pts treated with 731+NrtI. 731 continues to exhibit a favorable safety and tolerability profile in pts treated for over 1 year. The data support the continued development of 731.-
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 and safety of the hepatitis B core inhibitor ABI-H0731 administered with a nucleos(t)ide reverse transcriptase inhibitor in patients with HBeAg-positive chronic hepatitis B infection in a long-term extension study-
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)30790-X-
dc.identifier.hkuros315873-
dc.identifier.volume73-
dc.identifier.issueSuppl. 1-
dc.identifier.spageS140-
dc.identifier.epageS140-
dc.publisher.placeNetherlands-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats