Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China.
Gynecology and Obstetrics Center, the First Hospital of Jilin University, Changchun, China.
BMC Med. 2023 Mar 16;21(1):98. doi: 10.1186/s12916-023-02814-w.
Hepatitis B virus (HBV) core protein-targeting antivirals (CpTAs) are promising therapeutic agents for treating chronic hepatitis B (CHB). In this study, the antiviral activity, pharmacokinetics (PK), and tolerability of ZM-H1505R (Canocapavir), a chemically unique HBV CpTA, were evaluated in patients with CHB.
This study was a double-blind, randomized, placebo-controlled phase 1b trial in Chinese CHB patients. Noncirrhotic and treatment-naive CHB patients were divided into three cohorts (10 patients per cohort) and randomized within each cohort in a ratio of 4:1 to receive a single dose of 50, 100, or 200 mg of Canocapavir or placebo once a day for 28 consecutive days.
Canocapavir was well tolerated, with the majority of adverse reactions being grade I or II in severity. There were no serious adverse events, and no patients withdrew from the study. Corresponding to 50, 100, and 200 mg doses of Canocapavir, the mean plasma trough concentrations of the drug were 2.7-, 7.0-, and 14.6-fold of its protein-binding adjusted HBV DNA EC (135 ng/mL), respectively, with linear PK and a low-to-mild accumulation rate (1.26-1.99). After 28 days of treatment, the mean maximum HBV DNA declines from baseline were -1.54, -2.50, -2.75, and -0.47 log IU/mL for the 50, 100, and 200 mg of Canocapavir or placebo groups, respectively; and the mean maximum pregenomic RNA declines from baseline were -1.53, -2.35, -2.34, and -0.17 log copies/mL, respectively.
Canocapavir treatment is tolerated with efficacious antiviral activity in CHB patients, supporting its further development in treating HBV infection.
ClinicalTrials.gov, number NCT05470829).
乙型肝炎病毒（HBV）核心蛋白靶向抗病毒药物（CpTAs）是治疗慢性乙型肝炎（CHB）的有前途的治疗药物。在这项研究中，评估了 ZM-H1505R（Canocapavir）在 CHB 患者中的抗病毒活性、药代动力学（PK）和耐受性，ZM-H1505R 是一种化学上独特的 HBV CpTA。
这是一项在中国 CHB 患者中进行的双盲、随机、安慰剂对照的 1b 期研究。非肝硬化和未经治疗的 CHB 患者分为三个队列（每个队列 10 名患者），并在每个队列内按 4:1 的比例随机分为接受 50、100 或 200 mg 卡那卡培韦或安慰剂，每天一次，连续 28 天。
Canocapavir 耐受性良好，大多数不良反应严重程度为 1 级或 2 级。无严重不良事件，无患者退出研究。与 50、100 和 200 mg Canocapavir 剂量相对应，药物的平均血浆谷浓度分别为其蛋白结合调整 HBV DNA EC（135 ng/mL）的 2.7、7.0 和 14.6 倍，具有线性 PK 和低至中度蓄积率（1.26-1.99）。治疗 28 天后，与安慰剂组相比，Canocapavir 组的平均最大 HBV DNA 从基线下降分别为 -1.54、-2.50、-2.75 和 -0.47 log IU/mL；平均最大前基因组 RNA 从基线下降分别为 -1.53、-2.35、-2.34 和 -0.17 log 拷贝/mL。
Canocapavir 治疗 CHB 患者耐受良好，具有有效的抗病毒活性，支持其进一步开发用于治疗 HBV 感染。
ClinicalTrials.gov，编号 NCT05470829）。
