A Study of GSK3228836 in Participants With Chronic Hepatitis B (CHB)

Summary

Chronic hepatitis B virus (HBV) infection is a significant worldwide medical problem. GSK3228836 demonstrated target engagement in CHB participants who were not on treatment and in CHB participants on stable nucleos(t)ide therapy. This study is intended to evaluate if treatment with GSK3228836 can achieve sustained virologic response (SVR), that is hepatitis B virus surface antigen (HBsAg) less than (\<) lower limit of quantitation (LLOQ) and HBV deoxyribonucleic acid (DNA) \<LLOQ sustained for 24 weeks post-GSK3228836 treatment end. In addition, the study will also evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic properties of GSK3228836 in the 4 dosing regimens. This study will assess the efficacy and safety of treatment with GSK3228836 in two populations of participants with CHB; participants on stable nucleos(t)ide treatment (Cohort 1) and participants who are not currently on nucleos(t)ide therapy (Cohort 2). For each population, participants will be randomized into one of the 4 different parallel arms to receive treatment. The study will consist of a screening, treatment, and post-treatment follow-up phase. Approximately, 440 participants will be enrolled in the study.

Timeline

Start

2020-07-27

Primary completion

2022-03-18

Completion

2022-03-18

Publications

• Background Yuen MF, Lim SG, Plesniak R, Tsuji K, Janssen HLA, Pojoga C, Gadano A, Popescu CP, Stepanova T, Asselah T, Diaconescu G, Yim HJ, Heo J, Janczewska E, Wong A, Idriz N, Imamura M, Rizzardini G, Takaguchi K, Andreone P, Arbune M, Hou J, Park SJ, Vata A, Cremer J, Elston R, Lukic T, Quinn G, Maynard L, Kendrick S, Plein H, Campbell F, Paff M, Theodore D; B-Clear Study Group. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. N Engl J Med. 2022 Nov 24;387(21):1957-1968. doi: 10.1056/NEJMoa2210027. Epub 2022 Nov 8.
• Joshi S, Freudenberg JM, Singh JM, Jordan WT, Felton L, Dixon S, Paff M, Theodore D, Walker J. Immunomodulation by bepirovirsen may induce killing of infected hepatocytes (B-Together study). Hepatol Int. 2026 Feb;20(1):46-58. doi: 10.1007/s12072-025-10917-0. Epub 2025 Oct 3.
• Han K, Youssef AS, Magee M, Hood S, Tracey H, Kwoh J, Theodore D, Paff M, Nader A. Lack of Pharmacokinetic Drug-Drug Interactions Between Bepirovirsen and Nucleos(t)ide Analogs. Clin Pharmacol Drug Dev. 2025 Apr;14(4):281-291. doi: 10.1002/cpdd.1518. Epub 2025 Feb 14.
• Cremer J, Elston R, Campbell FM, Kendrick S, Paff M, Quinn G, Theodore D. B-Clear Phase 2b Study Design: Establishing the Efficacy and Safety of Bepirovirsen in Patients with Chronic Hepatitis B Virus Infection. Adv Ther. 2023 Sep;40(9):4101-4110. doi: 10.1007/s12325-023-02531-z. Epub 2023 Jul 1.

Drugs

Indications