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
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.