2. Academic Validation
  3. Safety, tolerability, pharmacokinetics, and antiviral activity of the novel core protein allosteric modulator ZM-H1505R (Canocapavir) in chronic hepatitis B patients: a randomized multiple-dose escalation trial

Safety, tolerability, pharmacokinetics, and antiviral activity of the novel core protein allosteric modulator ZM-H1505R (Canocapavir) in chronic hepatitis B patients: a randomized multiple-dose escalation trial

  • BMC Med. 2023 Mar 16;21(1):98. doi: 10.1186/s12916-023-02814-w.
Haiyan Jia 1 2,  Jiajia Mai 1,  Min Wu 1,  Hong Chen 1,  Xiaojiao Li 1,  Cuiyun Li 1,  Jingrui Liu 1,  Chengjiao Liu 1,  Yue Hu 1,  Xiaoxue Zhu 1,  Xiuhong Jiang 3,  Bo Hua 3,  Tian Xia 3,  Gang Liu 3,  Aiyun Deng 3,  Bo Liang 3,  Ruoling Guo 3,  Hui Lu 3,  Zhe Wang 3,  Huanming Chen 3,  Zhijun Zhang 3,  Hong Zhang 4,  Junqi Niu 5,  Yanhua Ding 6
Affiliations

Affiliations

  • 1 Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China.
  • 2 Gynecology and Obstetrics Center, the First Hospital of Jilin University, Changchun, China.
  • 3 Shanghai Zhimeng Biopharma, Inc, 1976 Gaoke Middle Road, Suite A-302, Pudong District, Shanghai, China.
  • 4 Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China. [email protected].
  • 5 Department of Hepatology, Center of Infectious Disease and Pathogen Biology, The First Hospital of Jilin University, Changchun, China. [email protected].
  • 6 Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China. [email protected].
PMID: 36927420 DOI: 10.1186/s12916-023-02814-w
Abstract

Background: 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.

Methods: 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.

Results: 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 EC50 (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 log10 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 log10 copies/mL, respectively.

Conclusions: Canocapavir treatment is tolerated with efficacious Antiviral activity in CHB patients, supporting its further development in treating HBV Infection.

Trial registration: ClinicalTrials.gov, number NCT05470829).

Keywords

Antiviral therapy; Clinical trial; Hepatitis B; Pharmacokinetics.

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