Dataset Information

Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients.

ABSTRACT:

Background/aims

Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection.

Methods

Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days.

Results

A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were -2.9, -3.3, -3.5 and -0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was -2.9, -2.4, -2.0, and -0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths.

Conclusion

In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.

SUBMITTER: Yuen MF

PROVIDER: S-EPMC11261219 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Publications

Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients.

Yuen Man-Fung MF Chuang Wan-Long WL Peng Cheng-Yuan CY Jeng Wen-Juei WJ Su Wei-Wen WW Chang Ting-Tsung TT Chen Chi-Yi CY Hsu Yao-Chun YC De La Rosa Guy G Ahmad Alaa A Luo Ed E Conery Annie L AL

Clinical and molecular hepatology 20240326 3

<h4>Background/aims</h4>Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection.<h4>Methods</h4>Patients with HBsAg detectable at screening and at least 6 months previously were e ...[more]

PMID: 38528825

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Dataset Information

Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients.

Background/aims

Methods

Results

Conclusion

Publications

Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients.

Similar Datasets

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