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Conference Paper: First clinical experience with RNA interference [RNAI]-based triple combination therapy in chronic hepatitis B (CHB): JNJ-73763989 (JNJ-3989), JNJ-56136379 (JNJ-6379) and a nucleos(t)ide analogue (NA)

TitleFirst clinical experience with RNA interference [RNAI]-based triple combination therapy in chronic hepatitis B (CHB): JNJ-73763989 (JNJ-3989), JNJ-56136379 (JNJ-6379) and a nucleos(t)ide analogue (NA)
Authors
Issue Date2019
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
The 70th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD): The Liver Meeting 2019, Boston, MA, USA, 8-12 November 2019. In Hepatology, 2019, v. 70 n. 6, p. 1489A, abstract no. LP4 How to Cite?
AbstractBackground: JNJ-3989 (RNAi) silences HBV RNA transcripts from integrated HBV DNA and episomal cccDNA. JNJ-6379 (novel class N capsid assembly modulator [CAM-N]; normal empty capsids) blocks HBV viral replication and de novo cccDNA formation in preclinical models, and reduced HBV DNA and RNA in CHB patients (pts) (AASLD 2018). AROHBV1001 showed that 3 monthly JNJ-3989 doses (100–400mg) with a NA: achieved >1 log10 HBsAg reductions; reduced all measurable viral products; was well tolerated (EASL 2019). Combining agents with different modes of action may lead to additive/synergistic antiviral effects, possibly increasing functional cure rates after finite treatment. To help design longer term studies, a cohort was added to explore triple combination therapy of JNJ-3989, JNJ6379 and a NA. Methods: HBeAg +ve or -ve, NA-experienced (regardless of HBV DNA level) or -naïve CHB pts were enrolled. 12 pts received 3 JNJ-3989 doses (200mg subcutaneously, days [D] 1, 29 and 57) + oral JNJ-6379 250mg once daily for 12 wks. Pts started/continued NA on D1 and continued beyond JNJ-6379 dosing. Assessments included safety, qHBsAg, qHBeAg, qHBV DNA, qHBV RNA and qHBcrAg levels. Planned follow-up is 1 yr with continued NA treatment. Results: All pts were Asian; median age 46 (34–67) yrs; 8 males; HBeAg 4 +ve 8 –ve; 7 NA-experienced. All pts had 3 JNJ-3989 doses and 84 days of JNJ-6379; follow-up was 17–64 days. No deaths, discontinuations, serious or severe adverse events (AEs) or clinically significant findings on vital signs/ECG/hematology/chemistry were reported. Two AEs (mild respiratory infection, not related) were reported. The only notable laboratory findings were grade 1 transient isolated ALT elevations (n=5, 57–118 U/L), possibly therapeutic response flares. HBsAg levels declined during treatment (Fig). Mean HBsAg (SE) log10 reductions were 1.4 (0.12) on D85 (n=12) and 1.8 (0.11) in 7 pts with D113 data. In pts with >1000 IU/mL HBV DNA on D1 (n=6, 3.7–7.7 log10 IU/mL), all had a rapid decline in DNA. 9 pts had quantifiable HBV RNA (D1, 1.75–7.5 log10 IU/mL); 6 were
DescriptionLate‐Breaking Poster Abstract - no. LP4
Persistent Identifierhttp://hdl.handle.net/10722/289898
ISSN
2019 Impact Factor: 14.679
2015 SCImago Journal Rankings: 4.752

 

DC FieldValueLanguage
dc.contributor.authorYuen, RMF-
dc.contributor.authorLocarnini, S-
dc.contributor.authorGiven, B-
dc.contributor.authorSchluep, T-
dc.contributor.authorHamilton, J-
dc.contributor.authorBiermer, M-
dc.contributor.authorKalmeijer, R-
dc.contributor.authorBeumont-Mauviel, M-
dc.contributor.authorLenz, O-
dc.contributor.authorCloherty, G-
dc.contributor.authorJackson, K-
dc.contributor.authorFerrari, C-
dc.contributor.authorLai, CL-
dc.contributor.authorLiu, SHK-
dc.contributor.authorMak, LY-
dc.contributor.authorWong, DKH-
dc.contributor.authorTo, WP-
dc.contributor.authorKo, KL-
dc.contributor.authorGish, RG-
dc.date.accessioned2020-10-22T08:19:03Z-
dc.date.available2020-10-22T08:19:03Z-
dc.date.issued2019-
dc.identifier.citationThe 70th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD): The Liver Meeting 2019, Boston, MA, USA, 8-12 November 2019. In Hepatology, 2019, v. 70 n. 6, p. 1489A, abstract no. LP4-
dc.identifier.issn0270-9139-
dc.identifier.urihttp://hdl.handle.net/10722/289898-
dc.descriptionLate‐Breaking Poster Abstract - no. LP4-
dc.description.abstractBackground: JNJ-3989 (RNAi) silences HBV RNA transcripts from integrated HBV DNA and episomal cccDNA. JNJ-6379 (novel class N capsid assembly modulator [CAM-N]; normal empty capsids) blocks HBV viral replication and de novo cccDNA formation in preclinical models, and reduced HBV DNA and RNA in CHB patients (pts) (AASLD 2018). AROHBV1001 showed that 3 monthly JNJ-3989 doses (100–400mg) with a NA: achieved >1 log10 HBsAg reductions; reduced all measurable viral products; was well tolerated (EASL 2019). Combining agents with different modes of action may lead to additive/synergistic antiviral effects, possibly increasing functional cure rates after finite treatment. To help design longer term studies, a cohort was added to explore triple combination therapy of JNJ-3989, JNJ6379 and a NA. Methods: HBeAg +ve or -ve, NA-experienced (regardless of HBV DNA level) or -naïve CHB pts were enrolled. 12 pts received 3 JNJ-3989 doses (200mg subcutaneously, days [D] 1, 29 and 57) + oral JNJ-6379 250mg once daily for 12 wks. Pts started/continued NA on D1 and continued beyond JNJ-6379 dosing. Assessments included safety, qHBsAg, qHBeAg, qHBV DNA, qHBV RNA and qHBcrAg levels. Planned follow-up is 1 yr with continued NA treatment. Results: All pts were Asian; median age 46 (34–67) yrs; 8 males; HBeAg 4 +ve 8 –ve; 7 NA-experienced. All pts had 3 JNJ-3989 doses and 84 days of JNJ-6379; follow-up was 17–64 days. No deaths, discontinuations, serious or severe adverse events (AEs) or clinically significant findings on vital signs/ECG/hematology/chemistry were reported. Two AEs (mild respiratory infection, not related) were reported. The only notable laboratory findings were grade 1 transient isolated ALT elevations (n=5, 57–118 U/L), possibly therapeutic response flares. HBsAg levels declined during treatment (Fig). Mean HBsAg (SE) log10 reductions were 1.4 (0.12) on D85 (n=12) and 1.8 (0.11) in 7 pts with D113 data. In pts with >1000 IU/mL HBV DNA on D1 (n=6, 3.7–7.7 log10 IU/mL), all had a rapid decline in DNA. 9 pts had quantifiable HBV RNA (D1, 1.75–7.5 log10 IU/mL); 6 were <limit of quantification by D29. Pts positive (D1) for HBeAg (n=4) and HBcrAg (n=8) all had reductions in these parameters. Conclusion: This is the first study to investigate the safety and efficacy of a triple combination of a RNAi (JNJ-3989), a CAM-N (JNJ-6739) and a NA in CHB pts. This combination was well tolerated and pts achieved robust reductions in HBsAg as well as other measurable viral parameters.-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/-
dc.relation.ispartofHepatology-
dc.relation.ispartofThe 70th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD): The Liver Meeting 2019-
dc.titleFirst clinical experience with RNA interference [RNAI]-based triple combination therapy in chronic hepatitis B (CHB): JNJ-73763989 (JNJ-3989), JNJ-56136379 (JNJ-6379) and a nucleos(t)ide analogue (NA)-
dc.typeConference_Paper-
dc.identifier.emailYuen, RMF: mfyuen@hku.hk-
dc.identifier.emailLai, CL: hrmelcl@hkucc.hku.hk-
dc.identifier.emailLiu, SHK: drkliu@hku.hk-
dc.identifier.emailMak, LY: lungyi@hku.hk-
dc.identifier.emailWong, DKH: danywong@hku.hk-
dc.identifier.authorityYuen, RMF=rp00479-
dc.identifier.authorityLai, CL=rp00314-
dc.identifier.authorityMak, LY=rp02668-
dc.identifier.authorityWong, DKH=rp00492-
dc.description.natureabstract-
dc.identifier.hkuros317233-
dc.identifier.volume70-
dc.identifier.issue6-
dc.identifier.spage1489A, abstract no. LP4-
dc.identifier.epage1489A, abstract no. LP4-
dc.publisher.placeUnited States-
dc.identifier.partofdoi10.1002/hep.31033-

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