vebicorvir 与恩替卡韦在初治慢性乙型肝炎病毒感染患者中的安

StephenW

vebicorvir 与恩替卡韦在初治慢性乙型肝炎病毒感染患者中的安全性和有效性
Mark S Sulkowski 1、Kosh Agarwal 2、Xiaoli Ma 3、Tuan T Nguyen 4、Eugene R Schiff 5、Hie-Won L Hann 6、Douglas T Dieterich 7、Ronald G Nahass 8、James S Park 9、Sing Chan 10、Steven -Huy B Han 11、Edward J Gane 12、Michael Bennett 13、Katia Alves 14、Marc Evanchik 14、Ran Yan 14、Qi Huang 14、Uri Lopatin 14、Richard Colonno 14、Julie Ma 14、Steven J Knox 14、Luisa M斯塔姆 14 ，毛里齐奥博纳奇尼 15 ，艾拉 M 雅各布森 9 ，瓦利德 S 阿尤布 16 ，弗兰克韦勒特 17 ，纳塔拉詹 拉文德兰 18 ，阿尔诺拉姆吉 19 ，保罗伊恩郭 20 ，玛格迪埃尔卡沙布 21 ，塔雷克哈桑 22 ，何 S 裴 23 ，雅各布拉勒扎里15 , Scott K Fung 24 , Man-Fung Yuen 25
隶属关系

    PMID: 35697332 DOI: 10.1016/j.jhep.2022.05.027

抽象的

背景和目的：核苷（酸）逆转录酶抑制剂不能完全抑制慢性HBV感染（cHBV）中的乙型肝炎病毒（HBV）DNA。 Vebicorvir (VBR) 是一种在研核心抑制剂，可干扰 HBV 复制的多个方面。该 2 期试验 (NCT03577171) 评估了 VBR 与恩替卡韦 (ETV) 联合用于未接受治疗的 cHBV 患者的疗效和安全性。

方法：乙型肝炎“e”抗原阳性、未接受过治疗的无肝硬化患者以双盲方式 1:1 随机分配至每日一次 VBR 300 mg+ETV 0.5 mg 或安慰剂 (PBO)+ETV 治疗 24 周（ W)。主要终点是平均 log10 HBV DNA 从基线到 W12 和 W24 的变化。

结果：两个治疗组（PBO+ETV：12/12；VBR+ETV：13/13）的所有患者均完成了研究。在第 12 周，与 PBO+ETV（-3.30 [1.18]；p=0.0077）相比，VBR+ETV 导致 log10 IU/mL HBV DNA（-4.45 [1.03]）较基线的平均 (SD) 降低更大。在第 24 周，与 PBO+ETV（-4.20 [0.98]；p=0.0084）相比，VBR+ETV 导致 log10 IU/mL HBV DNA（-5.33 [1.59]）较基线更大幅度减少。在第 12 周和第 24 周，在接受 VBR+ETV 与 PBO+ETV 的患者中观察到前基因组 RNA 的平均减少幅度更大（p<0.0001 和 p<0.0001）。两组病毒抗原的变化相似。未观察到 VBR 和 ETV 之间的药物相互作用。两名患者在治疗期间经历了 HBV DNA 反弹，未检测到耐药性突破。 VBR+ETV 的安全性与 PBO+ETV 相似。所有治疗中出现的不良事件和实验室异常均为 1/2 级。没有死亡、严重的 AE 或药物性肝损伤的证据。

结论：在这项为期 24 周的研究中，VBR+ETV 在未接受治疗的 cHBV 患者中提供了优于 PBO+ETV 的附加抗病毒活性，具有良好的安全性和耐受性。

总结：乙型肝炎是肝脏的长期病毒感染。该研究表明，与恩替卡韦单独治疗相比，恩替卡韦联合维比可韦（一种核心抑制剂）通常是安全的、耐受性良好的，并且在慢性感染乙型肝炎病毒的初治患者中表现出更强的抗病毒活性。本研究支持继续评估 vebicorvir 治疗慢性乙型肝炎。

临床试验编号：NCT03577171。

关键词：ABI-H0731；维比可韦；慢性乙型肝炎病毒；核心抑制剂；恩替卡韦；核苷（酸）逆转录酶抑制剂；阶段2;未经治疗。

版权所有 © 2022。Elsevier B.V. 出版
相关数据

    ClinicalTrials.gov/NCT03577171

StephenW

Safety and efficacy of vebicorvir administered with entecavir in treatment-naïve patients with chronic hepatitis B virus infection
Mark S Sulkowski  1 , Kosh Agarwal  2 , Xiaoli Ma  3 , Tuan T Nguyen  4 , Eugene R Schiff  5 , Hie-Won L Hann  6 , Douglas T Dieterich  7 , Ronald G Nahass  8 , James S Park  9 , Sing Chan  10 , Steven-Huy B Han  11 , Edward J Gane  12 , Michael Bennett  13 , Katia Alves  14 , Marc Evanchik  14 , Ran Yan  14 , Qi Huang  14 , Uri Lopatin  14 , Richard Colonno  14 , Julie Ma  14 , Steven J Knox  14 , Luisa M Stamm  14 , Maurizio Bonacini  15 , Ira M Jacobson  9 , Walid S Ayoub  16 , Frank Weilert  17 , Natarajan Ravendhran  18 , Alnoor Ramji  19 , Paul Yien Kwo  20 , Magdy Elkhashab  21 , Tarek Hassanein  22 , Ho S Bae  23 , Jacob P Lalezari  15 , Scott K Fung  24 , Man-Fung Yuen  25
Affiliations

    PMID: 35697332 DOI: 10.1016/j.jhep.2022.05.027

Abstract

Background and aims: Nucleos(t)ide reverse transcriptase inhibitors do not completely suppress hepatitis B virus (HBV) DNA in chronic HBV infection (cHBV). Vebicorvir (VBR) is an investigational core inhibitor which interferes with multiple aspects of HBV replication. This phase 2 trial (NCT03577171) evaluated the efficacy and safety of VBR in combination with entecavir (ETV) in treatment-naïve patients with cHBV.

Methods: Hepatitis B "e" antigen positive, treatment-naïve patients without cirrhosis were randomised 1:1 in a double-blind manner, to once-daily VBR 300 mg+ETV 0.5 mg or placebo (PBO)+ETV for 24 weeks (W). The primary endpoint was change in mean log10 HBV DNA from Baseline to W12 and W24.

Results: All patients in both treatment groups (PBO+ETV: 12/12; VBR+ETV: 13/13) completed the study. At W12, VBR+ETV led to a greater mean (SD) reduction from Baseline in log10 IU/mL HBV DNA (-4.45 [1.03]) vs PBO+ETV (-3.30 [1.18]; p=0.0077). At W24, VBR+ETV led to a greater reduction from Baseline in log10 IU/mL HBV DNA (-5.33 [1.59]) vs PBO+ETV (-4.20 [0.98]; p=0.0084). Greater mean reductions in pregenomic RNA were observed at W12 and W24 in patients receiving VBR+ETV vs PBO+ETV (p<0.0001 and p<0.0001). Changes in viral antigens were similar in both groups. No drug interaction between VBR and ETV was observed. Two patients experienced HBV DNA rebound during treatment, with no resistance breakthrough detected. Safety of VBR+ETV was similar to PBO+ETV. All treatment-emergent adverse events and laboratory abnormalities were Grade 1/2. There were no deaths, serious AEs, or evidence of drug-induced liver injury.

Conclusions: In this 24-week study, VBR+ETV provided additive antiviral activity over PBO+ETV in treatment-naïve patients with cHBV with a favourable safety and tolerability profile.

Lay summary: Hepatitis B is a long-lasting viral infection of the liver. This study demonstrates that vebicorvir (a core inhibitor) with entecavir is generally safe, well tolerated, and demonstrates greater antiviral activity compared with entecavir alone in treatment-naïve patients chronically infected with hepatitis B virus. This study supports continued evaluation of vebicorvir in the treatment of chronic hepatitis B.

Clinical trial number: NCT03577171.

Keywords: ABI-H0731; Vebicorvir; chronic hepatitis B virus; core inhibitor; entecavir; nucleos(t)ide reverse transcriptase inhibitor; phase 2; treatment-naïve.

Copyright © 2022. Published by Elsevier B.V.
Associated data

    ClinicalTrials.gov/NCT03577171