RNA Interference Therapy With ARC-520 Results in Prolonged Hepatitis B Surface Antigen Response in Patients With Chronic Hepatitis B Infection
DC Field | Value | Language |
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dc.contributor.author | Yuen M.-F. | - |
dc.contributor.author | Schiefke I. | - |
dc.contributor.author | Yoon J.-H. | - |
dc.contributor.author | Ahn S.H. | - |
dc.contributor.author | Heo J. | - |
dc.contributor.author | Kim J.H. | - |
dc.contributor.author | Lik Yuen Chan H. | - |
dc.contributor.author | Yoon K.T. | - |
dc.contributor.author | Klinker H. | - |
dc.contributor.author | Manns M. | - |
dc.contributor.author | Petersen J. | - |
dc.contributor.author | Schluep T. | - |
dc.contributor.author | Hamilton J. | - |
dc.contributor.author | Given B.D. | - |
dc.contributor.author | Ferrari C. | - |
dc.contributor.author | Lai C.-L. | - |
dc.contributor.author | Locarnini S.A. | - |
dc.contributor.author | Gish R.G. | - |
dc.date.available | 2020-07-30T01:35:26Z | - |
dc.date.created | 2020-05-06 | - |
dc.date.issued | 2020-07 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/71684 | - |
dc.description.abstract | Background and Aims: ARC-520, the first an RNA interference (RNAi) therapeutic, was designed to reduce all RNA transcripts derived from covalently closed circular DNA, leading to a reduction in viral antigens and hepatitis B virus (HBV) DNA. Approach and Results: We aimed to evaluate the depth of hepatitis B surface antigen (HBsAg) decline in response to multiple doses of ARC-520 compared to placebo (PBO) in two randomized, multicenter studies in nucleoside/nucleotide analogue reverse-transcriptase inhibitor (NUC)–experienced patients with hepatitis B early antigen (HBeAg)–negative (E-neg) or HBeAg-positive (E-pos) disease. A total of 58 E-neg and 32 E-pos patients were enrolled and received four monthly doses of PBO (n = 20 E-neg, 11 E-pos), 1 mg/kg ARC-520 (n = 17 E-neg, 10 E-pos), or 2 mg/kg ARC-520 (n = 21 E-neg, 11 E-pos) concomitantly with NUC. HBsAg change from baseline to 30 days after the last ARC-520 dose were compared to PBO. Both E-neg and E-pos high-dose groups significantly reduced HBsAg compared to PBO, with mean reductions of 0.38 and 0.54 log IU/mL, respectively. HBsAg reductions persisted for approximately 85 days and >85 days after the last dose in E-neg and E-pos patients, respectively. The low-dose groups did not reach statistical significance in either study. E-pos patients showed a dose-dependent reduction in HBeAg from baseline. Mean maximum reduction was 0.23 and 0.69 log Paul Ehrlich IUs/mL in the low-dose and high dose ARC-520 groups respectively. ARC-520 was well tolerated, with only two serious adverse events of pyrexia possibly related to study drug observed. Conclusions: ARC-520 was active in both E-neg and E-pos, NUC-experienced HBV patients; but absolute HBsAg reductions were moderate, possibly due to expression of HBsAg from integrated HBV DNA, indicating the need for RNAi therapeutics that can target viral transcripts regardless of origin. © 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | John Wiley and Sons Inc. | - |
dc.relation.isPartOf | Hepatology | - |
dc.title | RNA Interference Therapy With ARC-520 Results in Prolonged Hepatitis B Surface Antigen Response in Patients With Chronic Hepatitis B Infection | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000528490500001 | - |
dc.identifier.doi | 10.1002/hep.31008 | - |
dc.identifier.bibliographicCitation | Hepatology, v.72, no.1, pp.19 - 31 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85080930575 | - |
dc.citation.endPage | 31 | - |
dc.citation.startPage | 19 | - |
dc.citation.title | Hepatology | - |
dc.citation.volume | 72 | - |
dc.citation.number | 1 | - |
dc.contributor.affiliatedAuthor | Kim J.H. | - |
dc.type.docType | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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