Evidence map›Paper›PMID 31654573›Full record

Trial reportHepatology (Baltimore, Md.)2020

RNA Interference Therapy With ARC-520 Results in Prolonged Hepatitis B Surface Antigen Response in Patients With Chronic Hepatitis B Infection.

Man-Fung Yuen, Ingolf Schiefke, Jung-Hwan Yoon, Sang Hoon Ahn, Jeong Heo, Ju Hyun Kim, Henry Lik Yuen Chan, Ki Tae Yoon, Hartwig Klinker, Michael Manns and 8 more

Open access · hybridAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 3 pooled it
10.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

84 citing papers in PubMed, 3 syntheses or guidelines pooled it, 128 citations in OpenAlex.

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  8. [Clinical significance and occurrence mechanism of hepatitis B virus DNA integration].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
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24 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 8 institutions in 7 countries.

Man-Fung YuenQueen Mary Hospital, The University of Hong Kong, Hong Kong, China.
Ingolf SchiefkeEugastro Gmbh, Leipzig, Germany.
Jung-Hwan YoonSeoul National University Hospital, Seoul, Republic of Korea.
Sang Hoon AhnYonsei University College of Medicine, Seoul, Republic of Korea.
Jeong HeoPusan National University and Medical Research Institute, Busan, Republic of Korea.
Ju Hyun KimGachon University Gil Hospital, Incheon, Republic of Korea.
Henry Lik Yuen ChanThe Chinese University of Hong Kong, Hong Kong, China.
Ki Tae YoonPusan National University Yangsan Hospital, Yangsan-si, Republic of Korea.
Hartwig KlinkerUniversitaetsklinikum Wuerzburg, Wuerzburg, Germany.
Michael MannsMedizinische Hochschule Hannover, Hannover, Germany.
Joerg PetersenIFI Institute at Asklepios Klinik St. Georg, Hamburg, Germany.
Thomas SchluepArrowhead Pharmaceuticals, Inc., Pasadena, CA.ORCID 0000-0002-2986-7287
James HamiltonArrowhead Pharmaceuticals, Inc., Pasadena, CA.
Bruce D GivenArrowhead Pharmaceuticals, Inc., Pasadena, CA.
Carlo FerrariUnit of Infectious Diseases and Hepatology, University of Parma, Parma, Italy.
Ching-Lung LaiQueen Mary Hospital, The University of Hong Kong, Hong Kong, China.
Stephen A LocarniniVictorian Infectious Diseases Reference Laboratory, Melbourne, Australia.
Robert G GishDivision of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Stanford, CA.
Queen Mary Hospital · CNYonsei University · KRChinese University of Hong Kong · HKDeleted InstitutionPusan National University · KRPusan National University Yangsan Hospital · KRSeoul National University Hospital · KRUniversity of Parma · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsARC-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

resultsWe 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.

conclusionsARC-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.

Indexed as

RNAi TherapeuticsAdultAgedAntiviral AgentsDouble-Blind MethodDrug CombinationsFemaleGuanineHepatitis B, ChronicHepatitis B Surface AntigensHumansMaleMiddle AgedRNA, Small InterferingTenofovirTime FactorsAntiviral AgentsARC-520Drug CombinationsentecavirGuanineHepatitis B Surface AntigensRNA, Small InterferingTenofovir

Identifiers

PMID31654573
PMCPMC7496196
OpenAlexW2981927057

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.