File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Conference Paper: Viral response and safety following discontinuation of treatment with the core inhibitor vebicorvir and a nucleos (t)ide reverse transcriptase inhibitor in patients with HBeAg positive or negative chronic hepatitis B virus infection

TitleViral response and safety following discontinuation of treatment with the core inhibitor vebicorvir and a nucleos (t)ide reverse transcriptase inhibitor in patients with HBeAg positive or negative chronic hepatitis B virus infection
Authors
Issue Date2021
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
The International Liver Congress 2021 (ILC 2021): Beating Liver Disease Together, Virtual Conference, 23-26 June 2021, In Journal of Hepatology, 2021, v. 75 n. Suppl. 2, p. S736 How to Cite?
AbstractBackground and aims: Vebicorvir (VBR) is a 1st-generation core inhibitor being developed for chronic HBV infection (cHBV). In Study 201, NrtI-suppressed eAg pos or eAg neg cHBV patients (pts) with F0- F2 fibrosis were randomized to VBR or placebo +NrtI for 24 wks. Eligible pts then received VBR+NrtI in Study 211. VBR+NrtI resulted in deep on-treatment viral suppression assessed by high sensitivity assays. VBR+NrtI was discontinued if total HBV nucleic acid (DNA +pgRNA) was <20 U/ml and eAg negative or levels ≤5 IU/ml for ≥6 mths at Wk 52 or later. Here we report off-treatment (off-Rx) viral response and safety after VBR+NrtI discontinuation (DC) in Study 211. Method: The primary end point in Study 211 was sustained virologic response (SVR; HBV DNA <20 IU/ml, COBAS TaqMan v2.0) 24 wks off treatment. eAg and sAg were measured by Abbott Architect (LLOQ = 0.11 IU/ml, 0.05 IU/ml, respectively) and crAg by Lumipulse G (LOD = 1 kU/ml). Safety was assessed by adverse events (AEs) and labs. NrtI was restarted per protocol-specified criteria or investigator/pt preference. Results: Of the pts in Study 211, 18 of 43 eAg pos and 23 of 26 eAg neg pts discontinued VBR+NrtI. In these 41 pts, the mean age was 46 yrs, 71% male, 78% Asian, 80% on TFV and 20% on ETV. At time of DC, the mean duration of VBR treatment was 76 wks and NrtI was 6 yrs; the eAg pos pts had mean eAg 1.1 IU/ml, crAg 247 kU/ml and sAg 6595 IU/ml and the eAg neg pts had mean crAg 7.0 kU/ml and sAg 2808 IU/ml. No pt achieved SVR. Of the 18 eAg pos pts, 17 (94%) relapsed early at off-treatment (off-Rx) Wk 4 and 1 pt (6%) relapsed at off-Rx Wk 12. Of the 23 eAg neg pts, 16 (70%) relapsed early at off-Rx Wk 4, and 3 (13%) and 4 (17%) pts relapsed later at off-Rx Wk 12 and 16, respectively. Univariate logistic regression identified ETV use (p < 0.001) and lower crAg (p = 0.03) as associated with later relapse after off-Rx Wk 4. The current mean time off-Rx was 19 wks with 29/41 (71%) pts restarting NrtI with subsequent decline in HBV DNA. Off-Rx, 14/41 (34%) pts had AEs, most Grade 1 or 2. The most common AE was ALT elevation in 4/41 (10%) pts. No pt had confirmed ALT flare (≥10xULN) or hepatic decompensation. Two unrelated SAEs were reported, hemorrhage following surgery and seizure. Conclusion: While VBR+NrtI DC was well-tolerated, SVR was not achieved. Data suggest crAg level may be important in future DC criteria. Other studies with VBR+NrtI in multi-drug combinations will evaluate potential finite treatment regimens.
DescriptionLate breaker posters: Poster presentation: PO-482
Persistent Identifierhttp://hdl.handle.net/10722/305521
ISSN
2020 Impact Factor: 25.083
2020 SCImago Journal Rankings: 7.112

 

DC FieldValueLanguage
dc.contributor.authorGane, E-
dc.contributor.authorSulkowskI, M-
dc.contributor.authorMa, X-
dc.contributor.authorNguyen, T-
dc.contributor.authorHann, HW-
dc.contributor.authorHassanein, T-
dc.contributor.authorElkhashab, M-
dc.contributor.authorChan, S-
dc.contributor.authorNahass, R-
dc.contributor.authorBennett, M-
dc.contributor.authorPark, J-
dc.contributor.authorJacobson, I-
dc.contributor.authorBonacini, M-
dc.contributor.authorMa, J-
dc.contributor.authorYan, R-
dc.contributor.authorKnox, SJ-
dc.contributor.authorStamm, L-
dc.contributor.authorRamji, A-
dc.contributor.authorHan, SHB-
dc.contributor.authorAyoub, W-
dc.contributor.authorRavendhran, N-
dc.contributor.authorKwo, PY-
dc.contributor.authorDieterich, D-
dc.contributor.authorBae, H-
dc.contributor.authorSchiff, ER-
dc.contributor.authorLalezari, J-
dc.contributor.authorFung, S-
dc.contributor.authorYuen, RMF-
dc.date.accessioned2021-10-20T10:10:35Z-
dc.date.available2021-10-20T10:10:35Z-
dc.date.issued2021-
dc.identifier.citationThe International Liver Congress 2021 (ILC 2021): Beating Liver Disease Together, Virtual Conference, 23-26 June 2021, In Journal of Hepatology, 2021, v. 75 n. Suppl. 2, p. S736-
dc.identifier.issn0168-8278-
dc.identifier.urihttp://hdl.handle.net/10722/305521-
dc.descriptionLate breaker posters: Poster presentation: PO-482-
dc.description.abstractBackground and aims: Vebicorvir (VBR) is a 1st-generation core inhibitor being developed for chronic HBV infection (cHBV). In Study 201, NrtI-suppressed eAg pos or eAg neg cHBV patients (pts) with F0- F2 fibrosis were randomized to VBR or placebo +NrtI for 24 wks. Eligible pts then received VBR+NrtI in Study 211. VBR+NrtI resulted in deep on-treatment viral suppression assessed by high sensitivity assays. VBR+NrtI was discontinued if total HBV nucleic acid (DNA +pgRNA) was <20 U/ml and eAg negative or levels ≤5 IU/ml for ≥6 mths at Wk 52 or later. Here we report off-treatment (off-Rx) viral response and safety after VBR+NrtI discontinuation (DC) in Study 211. Method: The primary end point in Study 211 was sustained virologic response (SVR; HBV DNA <20 IU/ml, COBAS TaqMan v2.0) 24 wks off treatment. eAg and sAg were measured by Abbott Architect (LLOQ = 0.11 IU/ml, 0.05 IU/ml, respectively) and crAg by Lumipulse G (LOD = 1 kU/ml). Safety was assessed by adverse events (AEs) and labs. NrtI was restarted per protocol-specified criteria or investigator/pt preference. Results: Of the pts in Study 211, 18 of 43 eAg pos and 23 of 26 eAg neg pts discontinued VBR+NrtI. In these 41 pts, the mean age was 46 yrs, 71% male, 78% Asian, 80% on TFV and 20% on ETV. At time of DC, the mean duration of VBR treatment was 76 wks and NrtI was 6 yrs; the eAg pos pts had mean eAg 1.1 IU/ml, crAg 247 kU/ml and sAg 6595 IU/ml and the eAg neg pts had mean crAg 7.0 kU/ml and sAg 2808 IU/ml. No pt achieved SVR. Of the 18 eAg pos pts, 17 (94%) relapsed early at off-treatment (off-Rx) Wk 4 and 1 pt (6%) relapsed at off-Rx Wk 12. Of the 23 eAg neg pts, 16 (70%) relapsed early at off-Rx Wk 4, and 3 (13%) and 4 (17%) pts relapsed later at off-Rx Wk 12 and 16, respectively. Univariate logistic regression identified ETV use (p < 0.001) and lower crAg (p = 0.03) as associated with later relapse after off-Rx Wk 4. The current mean time off-Rx was 19 wks with 29/41 (71%) pts restarting NrtI with subsequent decline in HBV DNA. Off-Rx, 14/41 (34%) pts had AEs, most Grade 1 or 2. The most common AE was ALT elevation in 4/41 (10%) pts. No pt had confirmed ALT flare (≥10xULN) or hepatic decompensation. Two unrelated SAEs were reported, hemorrhage following surgery and seizure. Conclusion: While VBR+NrtI DC was well-tolerated, SVR was not achieved. Data suggest crAg level may be important in future DC criteria. Other studies with VBR+NrtI in multi-drug combinations will evaluate potential finite treatment regimens.-
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.ispartofThe International Liver Congress 2021 (ILC 2021)-
dc.titleViral response and safety following discontinuation of treatment with the core inhibitor vebicorvir and a nucleos (t)ide reverse transcriptase inhibitor in patients with HBeAg positive or negative chronic hepatitis B virus infection-
dc.typeConference_Paper-
dc.identifier.emailYuen, RMF: mfyuen@hku.hk-
dc.identifier.authorityYuen, RMF=rp00479-
dc.description.natureabstract-
dc.identifier.hkuros326607-
dc.identifier.volume75-
dc.identifier.issueSuppl. 2-
dc.identifier.spageS736-
dc.identifier.epageS736-
dc.publisher.placeNetherlands-
dc.identifier.partofdoi10.1016/S0168-8278(21)01843-2-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats