A Phase 2B, Randomized, Multi-Center, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Rencofilstat in Adult Subjects With Nonalcoholic Steatohepatitis and Advanced Liver Fibrosis

This is a randomized, double-blind, placebo-controlled, parallel-dosing, multi-center study to evaluate the efficacy and safety of Rencofilstat as evidenced by histopathological improvements in fibrosis in adult NASH subjects with F2 or F3 fibrosis (NASH CRN system). Antifibrotic biomarker activity will be evaluated on an exploratory basis.

开始日期2022-10-15

申办/合作机构

Hepion Pharmaceuticals, Inc.

EUCTR2021-005185-18-IT / Not yet recruiting临床2期

ASCEND-NASH: A PHASE 2B, RANDOMIZED, MULTI-CENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CRV431 IN ADULT SUBJECTS WITH NONALCOHOLIC STEATOHEPATITIS AND ADVANCED LIVER FIBROSIS - ASCEND-NASH

开始日期2022-10-05

申办/合作机构

Hepion Pharmaceuticals, Inc.

NCT05461105 / Completed临床2期

ALTITUDE NASH: A Phase 2, Randomized, Multi-Center, Open-Label Study to Evaluate the Safety and Efficacy of Rencofilstat in Adult Subjects With Nonalcoholic Steatohepatitis Stage 3 Fibrosis

This is a randomized, open-label, parallel-dosing, multi-center study to evaluate the safety and efficacy of rencofilstat as evidenced by assessing changes in the HepQuant Shunt Disease Severity Index Score (DSI), safety labs, and clinical events in adult NASH subjects with compensated Fibrosis stage F 2/3. Antifibrotic biomarker activity will be evaluated on an exploratory basis.

开始日期2022-03-15

申办/合作机构

Hepion Pharmaceuticals, Inc.

100 项与 CYPA x 乙肝病毒结构蛋白相关的临床结果

登录后查看更多信息

100 项与 CYPA x 乙肝病毒结构蛋白相关的转化医学

登录后查看更多信息

0 项与 CYPA x 乙肝病毒结构蛋白相关的专利（医药）

登录后查看更多信息

项与 CYPA x 乙肝病毒结构蛋白相关的文献（医药）

2016-09-01·VirusDisease

Prediction of HBF-0259 interactions with hepatitis B Virus receptors and surface antigen secretory factors

Article

作者: Memarian, Ali ; Mohebbi, Alireza ; Mohammadi, Saeed

Hepatitis B virus (HBV) is an etiological agent of viral hepatitis, which may lead to cirrhosis, and hepatocellular carcinoma. Current treatment strategies have not shown promising effect to date but various complications such as, drug toxicity-resistance have been reported. Study on newly discovered compounds, with minimal side effects, as specific HBV inhibitors is a fundamental subject introducing new biologic drugs. Here, we aimed to, by prediction, estimate interactions of HBF-0259 as a non-toxic anti-HBV compound on inhibiting the HBV through either interaction with the viral entry or HBsAg secreting factors using In Silico procedure. Molecular docking was performed by Hex 8.0.0 software to predict the interaction energy (Etot) between HBF-0259 and known cellular factors involved in HBV entry and HBsAg secreting factors. Hex 8.0.0 also employed to create protein-protein complexes. These interactions were then used to analyze the binding site of HBF-0259 within the assumed receptors by MGLTools software. Finally, the amino acid sequences involved in this interaction were aligned for any conservancy. Here, we showed that HBF-0259 Etot with CypA (-545.41 kcal/mol) and SCCA1 (499.68 kcal/mol), involved in HBsAg secretion and HBV integration, respectively, was higher than other interactions. Furthermore, HBF-0259 predicted interaction energy was even higher than those of CypA inhibitors. In addition, we claim that preS1 and/or preS2 regions within HBsAg are not suitable targets for HBF-0259. HBF-0259 has higher interaction energy with CypA and SCCA1, even more than other known receptors, co-receptors, viral ligands, and secretory factors. HBF-0259 could be introduced as potent anti-viral compound in which CypA and or SCCA1, as previously shown, are involved.

2015-02-01·Gastroenterology1区 · 医学

Alisporivir Inhibition of Hepatocyte Cyclophilins Reduces HBV Replication and Hepatitis B Surface Antigen Production

1区 · 医学

Article

作者: Riva, Antonio ; Williams, Roger ; Chokshi, Shilpa ; Chatterji, Udayan ; Gallay, Philippe ; Bobardt, Michael ; Naoumov, Nikolai V ; Phillips, Sandra

BACKGROUND & AIMSCyclophilins are host factors required for hepatitis C virus replication. Cyclophilin inhibitors such as alisporivir have shown strong anti-hepatitis C virus activity in vitro and in clinical studies. However, little is known about whether hepatocyte cyclophilins are involved in the hepatitis B virus (HBV) life cycle. We investigated the effects of 2 cyclophilin inhibitors (alisporivir and NIM811) on HBV replication and hepatitis B surface antigen (HBsAg) production in cell lines.METHODSLiver-derived cell lines producing full-length HBV and HBsAg particles, owing to stable (HepG2215) or transient (HuH-7) transfection, or infected with HBV (HepaRG cells; Invitrogen [Carlsbad, CA]), were incubated with alisporivir or NIM811 alone, or alisporivir in combination with a direct antiviral (telbivudine). The roles of individual cyclophilins in drug response was evaluated by small interfering RNA knockdown of cyclophilin (CYP)A, CYPC, or CYPD in HepG2215 cells, or CYPA knockdown in HuH-7 cells. The kinetics of antiviral activity were assessed based on levels of HBV DNA and HBsAg and Southern blot analysis.RESULTSIn HepG2215, HuH-7, and HepaRG cells, alisporivir reduced intracellular and secreted HBV DNA, in a dose-dependent manner. Knockdown of CYPA, CYPC, or CYPD (reduced by 80%) significantly reduced levels of HBV DNA and secreted HBsAg. Knockdown of CYPA significantly reduced secretion of HBsAg, leading to accumulation of intracellular HBsAg; the addition of alisporivir greatly reduced levels of HBsAg in these cells. The combination of alisporivir and telbivudine had greater antiviral effects than those of telbivudine or alisporivir alone.CONCLUSIONSAlisporivir inhibition of cyclophilins in hepatocyte cell lines reduces replication of HBV DNA and HBsAg production and secretion. These effects are potentiated in combination with direct antiviral agents that target HBV-DNA polymerase.

2007-10-01·Journal of Medical Virology4区 · 医学

Proteomic analysis of hepatitis B surface antigen positive transgenic mouse liver and decrease of cyclophilin A

4区 · 医学

Article

作者: Peng-Yuan Yang ; Yu-Mei Wen ; Long Wang ; Cai-Yun Fang ; Xiao-Chen Tian ; Chao Zhao

AbstractThe small, 22‐nm spherical particles associated with hepatitis B infection are composed of hepatitis B surface antigen (HBsAg) and usually outnumber the virions by a ratio of 102 or 103. To study the interactions and pathogenesis between liver cells and the expression of HBsAg, global protein profiles were compared by two dimensional gel‐based differential proteomics between the livers of a lineage of HBsAg positive transgenic mice and their HBsAg negative control siblings. A total of 93 proteins were identified in the HBV transgenic mice. Around 45% of these differentially expressed proteins were enzymes associated with metabolism, suggesting that the processing of lipids, carbohydrates and certain amino acids were up‐ or down‐regulated. Among these proteins, cyclophilin A (CypA), the major target for the potent immunosuppressive drug cyclosporin A, was found decreased in HBsAg positive transgenic mouse liver and in a stable cell line expressing HBsAg when compared to their controls. The decrease of intracellular CypA was accompanied by an increased secretion of this protein into the supernatant of HBsAg positive cells. Possible implications of HBsAg expression and the intracellular decrease of CypA are discussed. J. Med. Virol. 79:1478–1484, 2007. © Wiley‐Liss, Inc.