A Multicenter, Randomized, Controlled, Open-label Phase IIb Study to Assess Efficacy and Safety of HH-003 Injection in Subjects With Chronic Hepatitis Delta Virus Infection

This is a multicenter, randomized, controlled, open-label, Phase IIb study of HH-003 injection, HH-003 injection is a monoclonal antibody targeting Hepatitis B virus. This study aims to assess efficacy and safety in subjects with chronic hepatitis delta virus infection.

开始日期2023-06-16

申办/合作机构

华辉安健（北京）生物科技有限公司

CTR20231354 / Active, not recruiting临床2期

一项在慢性丁型肝炎病毒感染者中评估HH-003注射液的疗效和安全性的多中心、随机、对照的开放性IIb期临床研究

根据主要终点评估HH-003注射液不同剂量组相较对照组治疗慢性HDV感染者的有效性

开始日期2023-05-23

申办/合作机构

华辉安健（北京）生物科技有限公司

NCT05734807 / Completed临床2期

A Multicenter, Randomized, Controlled Phase IIa Study to Evaluate the Antiviral Activity and Safety of HH-003 in Nucleos(t)Ide Analogues-treated Chronic Hepatitis B Subjects With Low-Level Viremia

This is a multicenter, randomized, controlled Phase IIa study of HH-003 to evaluate the antiviral activity and safety in nucleos(t)ide analogues-treated chronic hepatitis B subjects with low-level viremia. HH-003 is a human monoclonal antibody targeting the pre-S1 domain of the HBV large envelope protein. It blocks engagement of preS1 with sodium taurocholate co-transporting polypeptide (NTCP), the cellular receptor for HBV.

开始日期2022-07-20

申办/合作机构

华辉安健（北京）生物科技有限公司

100 项与 HBV pre-S1 相关的临床结果

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100 项与 HBV pre-S1 相关的转化医学

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0 项与 HBV pre-S1 相关的专利（医药）

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项与 HBV pre-S1 相关的文献（医药）

2015-08-10·Current Pharmaceutical Biotechnology4区 · 医学

Isolation of the neutralization ScFvs against HBV infection from the immunized population

4区 · 医学

Article

作者: Xu, Pengfei ; Qi, Jianying ; Li, Deshan ; Bai, Yin ; Chen, Yanmin ; Zhao, Jingzhuang ; Wang, Wenfei ; Yuan, Qingyan ; Zhang, Nan ; Wang, Fuxiang ; Ren, Guiping ; Guo, Xiaochen

For a long time, researchers have attempted to replace human plasmaderived immunoglobulin against HBV with recombinant HBV antibodies for therapeutic purposes, but failed to develop the products. One of the reasons may be lack of high throughput antibody screening tool. In this study, we screened an antibody library from immunized subjects by a powerful bacterial display technology. The capacity of the ScFv library was 10(9), 117 individual clones against HBV pre- S1 were initially selected and sequenced, the homology of these clones ranged from 59.7% -68.7%. Ten clones were randomly selected based on florescence intensity by FACS. The ScFv antibodies were expressed in E.coli and purified to examine their neutralization ability. First, we tested the ability of these clones to block the binding of the pre-S1 polypeptide to the HBV sensitive cells Chang liver cells and HepG2 cells, then, we examined the ability of these clones to inhibit the infection of the Change liver cells by HBV released from HepG2.2.15 cells by detection of viral DNA and hepatitis B virus e antigen (HBeAg) in the supernatant of Chang liver cells. Results showed that 4 (clone 3, 7, 9 and 31) out of the ten clones could significantly reduce the binding of pre-S1 polypeptide to Chang liver cells in a dose-dependent manner. Treatment with the same clones (clone 3, 7, 9 and 31) could dramatically reduce the contents of HBV DNA in the media of the infected Chang liver cells by 29.4, 7.89, 58.8, 76.9, respectively, and the amount of HBeAg by 60.2%, 32.6%, 66.1% and 68.1%, respectively. These results suggest that these clones can neutralize HBV infection and have the potential to become therapeutic antibodies against HBV infection to replace the human plasma-derived immunoglobulin.

2010-02-15·Journal of Virology2区 · 医学

Fine Mapping of Pre-S Sequence Requirements for Hepatitis B Virus Large Envelope Protein-Mediated Receptor Interaction

2区 · 医学

Article

作者: Schieck, Alexa ; Schulze, Andreas ; Mier, Walter ; Ni, Yi ; Urban, Stephan

ABSTRACT Previous studies showed that the N-terminal 75 amino acids of the pre-S1 domain of the hepatitis B virus (HBV) L protein are essential for HBV and hepatitis delta virus (HDV) infectivity. Consistently, synthetic lipopeptides encompassing this sequence or only parts of it efficiently block HBV and HDV infection, presumably through specific interference with a cellular receptor. Crucial for both virus infectivity and the inhibitory activity of the peptides are N-terminal myristoylation and a highly conserved motif within the N-terminal 48 amino acids. To refine the sequence requirements, we synthesized a series of HBV pre-S1 peptides containing deletions, point mutations, d -amino acid exchanges, or genotype-specific sequence permutations. Using the HepaRG cell line and a genotype D-derived virus, we determined the specific inhibitory activities of the peptides and found that (i) lipopeptides with an artificial consensus sequence inhibit HBV genotype D infection more potently than the corresponding genotype D peptides; (ii) point mutations, d -amino acid exchanges, or deletions introduced into the highly conserved part of the pre-S1 domain result in an almost complete loss of activity; and (iii) the flanking sequences comprising amino acids 2 to 8, 16 to 20, and, to a less pronounced extent, 34 to 48 gradually increase the inhibitory activity, while amino acids 21 to 33 behave indifferently. Taken together, our data suggest that HBV pre-S1-mediated receptor interference and, thus, HBV receptor recognition form a highly specific process. It requires an N-terminal acyl moiety and a highly conserved sequence that is present in primate but not rodent or avian hepadnaviruses, indicating different entry pathways for the different family members.

2004-12-01·Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology

[Advance in research of hepatitis B virus pre-S1 antigen].

Review

作者: He, Hua ; Zhang, Da-Zhi