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Article: Antiviral Activity, Safety, and Pharmacokinetics of Capsid Assembly Modulator NVR 3-778 in Patients with Chronic HBV Infection

TitleAntiviral Activity, Safety, and Pharmacokinetics of Capsid Assembly Modulator NVR 3-778 in Patients with Chronic HBV Infection
Authors
KeywordsEncapsidation
Capsid Inhibitor
Hepatitis B Treatment
Clinical Trial
Issue Date2019
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastro
Citation
Gastroenterology, 2019, v. 156 n. 5, p. 1392-1403.e7 How to Cite?
AbstractBackground & Aims: NVR 3-778 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator that can inhibit HBV replication. We performed a proof-of-concept study to examine the safety, pharmacokinetics, and antiviral activity of NVR 3-778 in patients with chronic HBV infection. Methods: We performed a phase 1 study in 73 hepatitis B envelope antigen (HBeAg)-positive patients with chronic HBV infection without cirrhosis. In a 2-part study (part 1 in New Zealand and part 2 in Hong Kong, Singapore, Taiwan, Korea, and the United States), patients were randomly assigned to groups that were given oral NVR 3-778 (100 mg, 200 mg, or 400 mg daily or 600 mg or 1000 mg twice daily) or placebo for 4 weeks. Additional groups received combination treatment with pegylated interferon (pegIFN) and NVR 3-778 (600 mg twice daily) or pegIFN with placebo. Results: Reductions in serum levels of HBV DNA and HBV RNA were observed in patients receiving ≥1200 mg/d NVR 3-778. The largest mean reduction in HBV DNA was observed in the group given NVR 3-778 plus pegIFN (1.97 log10 IU/mL), compared with the groups given NVR 3-778 or pegIFN alone (1.43 log10 IU/mL and 1.06 log10 IU/mL, respectively). The mean reduction in HBV RNA was also greatest in the group given NVR 3-778 plus pegIFN (2.09 log10 copies/mL), compared with the groups given NVR 3-778 or pegIFN alone (1.42 log10 copies/mL and 0.89 log10 copies/mL, respectively). There was no significant mean reduction in HBsAg during the 4-week treatment period. There were no discontinuations and no pattern of dose-related adverse effects with NVR 3-778. Conclusions: In a phase 1 study of HBeAg-positive patients with chronic HBV infection without cirrhosis, NVR 3-778 was well tolerated and demonstrated antiviral activity. The agent reduced serum levels of HBV DNA and HBV RNA, to the greatest extent in combination with pegIFN. The observed reductions in HBV RNA confirmed the novel mechanism of NVR 3-778. Clinicaltrials.gov no. NCT02112799 (single-center) and NCT02401737 (multicenter).
Persistent Identifierhttp://hdl.handle.net/10722/275108
ISSN
2017 Impact Factor: 20.773
2015 SCImago Journal Rankings: 7.170

 

DC FieldValueLanguage
dc.contributor.authorYuen, MF-
dc.contributor.authorGane, EJ-
dc.contributor.authorKim, DJ-
dc.contributor.authorWeilert, F-
dc.contributor.authorChan, HLY-
dc.contributor.authorLalezari, J-
dc.contributor.authorHwang, SG-
dc.contributor.authorNguyen, T-
dc.contributor.authorFlores, O-
dc.contributor.authorHartman, G-
dc.contributor.authorLiaw, S-
dc.contributor.authorLenz, O-
dc.contributor.authorKakuda, TN-
dc.contributor.authorTalloen, W-
dc.contributor.authorSchwabe, C-
dc.contributor.authorKlumpp, K-
dc.contributor.authorBrown, N-
dc.date.accessioned2019-09-10T02:35:37Z-
dc.date.available2019-09-10T02:35:37Z-
dc.date.issued2019-
dc.identifier.citationGastroenterology, 2019, v. 156 n. 5, p. 1392-1403.e7-
dc.identifier.issn0016-5085-
dc.identifier.urihttp://hdl.handle.net/10722/275108-
dc.description.abstractBackground & Aims: NVR 3-778 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator that can inhibit HBV replication. We performed a proof-of-concept study to examine the safety, pharmacokinetics, and antiviral activity of NVR 3-778 in patients with chronic HBV infection. Methods: We performed a phase 1 study in 73 hepatitis B envelope antigen (HBeAg)-positive patients with chronic HBV infection without cirrhosis. In a 2-part study (part 1 in New Zealand and part 2 in Hong Kong, Singapore, Taiwan, Korea, and the United States), patients were randomly assigned to groups that were given oral NVR 3-778 (100 mg, 200 mg, or 400 mg daily or 600 mg or 1000 mg twice daily) or placebo for 4 weeks. Additional groups received combination treatment with pegylated interferon (pegIFN) and NVR 3-778 (600 mg twice daily) or pegIFN with placebo. Results: Reductions in serum levels of HBV DNA and HBV RNA were observed in patients receiving ≥1200 mg/d NVR 3-778. The largest mean reduction in HBV DNA was observed in the group given NVR 3-778 plus pegIFN (1.97 log10 IU/mL), compared with the groups given NVR 3-778 or pegIFN alone (1.43 log10 IU/mL and 1.06 log10 IU/mL, respectively). The mean reduction in HBV RNA was also greatest in the group given NVR 3-778 plus pegIFN (2.09 log10 copies/mL), compared with the groups given NVR 3-778 or pegIFN alone (1.42 log10 copies/mL and 0.89 log10 copies/mL, respectively). There was no significant mean reduction in HBsAg during the 4-week treatment period. There were no discontinuations and no pattern of dose-related adverse effects with NVR 3-778. Conclusions: In a phase 1 study of HBeAg-positive patients with chronic HBV infection without cirrhosis, NVR 3-778 was well tolerated and demonstrated antiviral activity. The agent reduced serum levels of HBV DNA and HBV RNA, to the greatest extent in combination with pegIFN. The observed reductions in HBV RNA confirmed the novel mechanism of NVR 3-778. Clinicaltrials.gov no. NCT02112799 (single-center) and NCT02401737 (multicenter).-
dc.languageeng-
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastro-
dc.relation.ispartofGastroenterology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectEncapsidation-
dc.subjectCapsid Inhibitor-
dc.subjectHepatitis B Treatment-
dc.subjectClinical Trial-
dc.titleAntiviral Activity, Safety, and Pharmacokinetics of Capsid Assembly Modulator NVR 3-778 in Patients with Chronic HBV Infection-
dc.typeArticle-
dc.identifier.emailYuen, MF: mfyuen@hku.hk-
dc.identifier.authorityYuen, MF=rp00479-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1053/j.gastro.2018.12.023-
dc.identifier.pmid30625297-
dc.identifier.scopuseid_2-s2.0-85063411210-
dc.identifier.hkuros304384-
dc.identifier.volume156-
dc.identifier.issue5-
dc.identifier.spage1392-
dc.identifier.epage1403.e7-
dc.publisher.placeUnited States-
dc.identifier.f1000734831079-

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