JNJ-64530440（一种新型衣壳组装调节剂）的安全性、抗病毒活

StephenW

JNJ-64530440（一种新型衣壳组装调节剂）的安全性、抗病毒活性和药代动力学，作为 4 周单药治疗初治慢性乙型肝炎病毒感染患者
Ed J Gane 1、Christian Schwabe 2、Elina Berliba 3 4、Pisit Tangkijvanich 5、Alina Jucov 3 4、Nelea Ghicavii 3、Thierry Verbinnen 6、Oliver Lenz 6、Willem Talloen 6、Thomas N Kakuda 7、Chris Westland 7、Megha Patel 7、Jeysen Z Yogaratnam 7、Leonard Dragone 7、Pieter Van Remoortere 8
隶属关系
隶属关系

    1
    新西兰奥克兰大学新西兰肝移植中心。
    2
    奥克兰临床研究，奥克兰，新西兰。
    3
    ARENSIA 探索医学，共和国临床医院，基希讷乌，摩尔多瓦。
    4
    摩尔多瓦基希讷乌国立医药大学 N. Testemitanu。
    5
    泰国曼谷朱拉隆功大学医学院肝炎和肝癌卓越中心。
    6
    Janssen Pharmaceutica, NV, Beerse, 比利时。
    7
    Janssen BioPharma Inc.，美国加利福尼亚州南旧金山。
    8
    Janssen Pharmaceuticals，美国新泽西州泰特斯维尔。

    PMID：35040959 DOI：10.1093/jac/dkab491

抽象的

目的：我们研究了 JNJ-64530440（一种乙型肝炎病毒衣壳组装调节剂）在慢性乙型肝炎 (CHB) 患者中的安全性、抗病毒活性和药代动力学（1b 期，NCT03439488）。

方法：20 名初治、HBeAg 阳性或阴性 CHB 患者被随机分配到 JNJ-64530440 750 mg 每天一次或两次，或安慰剂治疗 28 天。

结果：所有患者（平均年龄 43.8 岁；85% 男性；70% 白人；20% HBeAg 阳性）完成给药/28 天随访。 3/4（安慰剂）、6/8（每天一次）和 4/8（每天两次）的患者出现轻度至中度治疗中出现的不良事件；主要是疲劳、丙氨酸氨基转移酶升高、中性粒细胞计数减少和头痛。乙型肝炎病毒 (HBV) DNA 大幅减少；第 29 天与基线的平均（范围）变化为：-3.2（-2.4 至 -3.9）（每天一次）和 -3.3（-2.6 至 -4.1）（每天两次）log10 IU/mL；安慰剂 0.1（0.7 至 -0.6）log10 IU/mL。 5/8（每天一次）和 3/8（每天两次）患者的 HBV DNA 水平低于定量下限 (LLOQ)。对于可检测到基线 HBV RNA 的患者，第 29 天时 HBV RNA 与基线的平均 (SE) 变化分别为：-2.65 (0.81)（每天一次）和 -2.94 (0.33)（每天两次）log10 拷贝/mL。 4/6（每天一次）和 3/7（每天两次）患者的 HBV RNA 水平是“未检测到目标”。 JNJ-64530440 在 CHB 患者中的药代动力学与健康志愿者相当。

结论：JNJ-64530440 750 mg 每天一次或每天两次，持续 28 天，在 CHB 患者中具有良好的耐受性并达到了有效的抗病毒活性。

© 作者 2022。牛津大学出版社代表英国抗菌化疗学会出版。

StephenW

Safety, antiviral activity and pharmacokinetics of JNJ-64530440, a novel capsid assembly modulator, as 4 week monotherapy in treatment-naive patients with chronic hepatitis B virus infection
Ed J Gane  1 , Christian Schwabe  2 , Elina Berliba  3   4 , Pisit Tangkijvanich  5 , Alina Jucov  3   4 , Nelea Ghicavii  3 , Thierry Verbinnen  6 , Oliver Lenz  6 , Willem Talloen  6 , Thomas N Kakuda  7 , Chris Westland  7 , Megha Patel  7 , Jeysen Z Yogaratnam  7 , Leonard Dragone  7 , Pieter Van Remoortere  8
Affiliations
Affiliations

    1
    New Zealand Liver Transplant Unit, University of Auckland, Auckland, New Zealand.
    2
    Auckland Clinical Studies, Auckland, New Zealand.
    3
    ARENSIA Exploratory Medicine, Republican Clinical Hospital, Chisinau, Moldova.
    4
    State University of Medicine and Pharmacy N. Testemitanu, Chisinau, Moldova.
    5
    Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
    6
    Janssen Pharmaceutica, NV, Beerse, Belgium.
    7
    Janssen BioPharma Inc., South San Francisco, CA, USA.
    8
    Janssen Pharmaceuticals, Titusville, NJ, USA.

    PMID: 35040959 DOI: 10.1093/jac/dkab491

Abstract

Objectives: We investigated JNJ-64530440 (a hepatitis B virus capsid assembly modulator) safety, antiviral activity and pharmacokinetics in patients with chronic hepatitis B (CHB) (Phase 1b, NCT03439488).

Methods: Twenty treatment-naive, HBeAg-positive or -negative CHB patients were randomized 4‍:‍1 to JNJ-64530440 750 mg once or twice daily, or placebo for 28 days.

Results: All patients (mean age 43.8 years; 85% male; 70% White; 20% HBeAg positive) completed dosing/28 day follow-up. Mild-to-moderate treatment-emergent adverse events occurred in 3/4 (placebo), 6/8 (once-daily) and 4/8 (twice-daily) patients; mostly fatigue, increased alanine aminotransferase, decreased neutrophil count, and headache. Hepatitis B virus (HBV) DNA was substantially reduced; mean (range) changes from baseline at day 29 were: -3.2 (-2.4 to -3.9) (once-daily) and -3.3 (-2.6 to -4.1) (twice-daily) log10 IU/mL; placebo 0.1 (0.7 to -0.6) log10 IU/mL. HBV DNA levels were below the lower limit of quantification (LLOQ) in 5/8 (once-daily) and 3/8 (twice-daily) patients. For patients with detectable baseline HBV RNA, mean (SE) changes versus baseline in HBV RNA at day 29 were: -2.65 (0.81) (once-daily) and -2.94 (0.33) (twice-daily) log10 copies/mL. HBV RNA levels were 'target not detected' in 4/6 (once-daily) and 3/7 (twice-daily) patients. JNJ-64530440 pharmacokinetics in CHB patients were comparable with those in healthy volunteers.

Conclusions: JNJ-64530440 750 mg once-daily or twice-daily for 28 days was well tolerated and achieved potent antiviral activity in CHB patients.

© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.