A Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK3389404 in Chronic Hepatitis B (CHB) Subjects

Summary

GSK3389404 is being developed for the treatment of CHB virus infection. The development goal for GSK3389404 is the establishment of a finite duration treatment that results in sustained suppression of hepatitis B virus (HBV) replication and viral antigen production after cessation of all treatments for CHB due to the restoration of a functional immune response in the absence of high antigen levels. This study is a multicenter, randomized double-Blind (sponsor un-blinded in Part 1), Placebo-controlled Study which will evaluate the safety, tolerability, PK, and PD profile of GSK3389404 in subjects with CHB and aim to establish proof-of-mechanism. The study will be conducted in two parts. Part 1 plans to enroll subjects primarily from the Asia-pacific region, including Japan and will be conducted as a single ascending dose (SAD) study with 5 planned cohorts ranging from 30 milligram (mg) to a maximum of 240 mg GSK3389404. Within each cohort, subjects will be randomized to receive either GSK3389404 or placebo in a 3:1 ratio. Cohorts A, B, C, C1, and D will be conducted in a sequential fashion; Cohort C1 is an optional cohort and may be dosed after Cohort C or in parallel with Cohort D. Part 2 will be conducted as a multiple-dose, dose-ranging study. Subjects will be randomized to different parallel dose levels and regimens or placebo. The dose levels of Part 2 will be selected after a review of Part 1 safety, Pharmacokinetic (PK) and Pharmacodynamic (PD) data. The treatments selected are 60 mg GSK3389404 weekly, 120 mg GSK3389404 bi-weekly, 120 mg GSK3389404 weekly or placebo. An optional Japanese part-2 sub-study is planned. The total study duration for part 1 including screening, treatment, and post-treatment follow-up, will not be expected to exceed 13 weeks for each subject and for part 2, including screening, treatment and post-treatment follow-up, will not be expected to exceed 65 weeks for each subject.

Timeline

Start

2017-02-14

Primary completion

2019-01-28

Completion

2019-11-06

Publications

• Han K, Theodore D, McMullen G, Swayze E, McCaleb M, Billioud G, Wieland S, Hood S, Paff M, Bennett CF, Kwoh TJ. Preclinical and Phase 1 Assessment of Antisense Oligonucleotide Bepirovirsen in Hepatitis B Virus-Transgenic Mice and Healthy Human Volunteers: Support for Clinical Dose Selection and Evaluation of Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses. Clin Pharmacol Drug Dev. 2022 Oct;11(10):1191-1202. doi: 10.1002/cpdd.1154. Epub 2022 Aug 16.
• Yuen MF, Heo J, Kumada H, Suzuki F, Suzuki Y, Xie Q, Jia J, Karino Y, Hou J, Chayama K, Imamura M, Lao-Tan JY, Lim SG, Tanaka Y, Xie W, Yoon JH, Duan Z, Kurosaki M, Park SJ, Labio ME, Kumar R, Kweon YO, Yim HJ, Tao Y, Cremer J, Elston R, Davies M, Baptiste-Brown S, Han K, Campbell FM, Paff M, Theodore D. Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy. J Hepatol. 2022 Oct;77(4):967-977. doi: 10.1016/j.jhep.2022.05.031. Epub 2022 Jun 15.

Drugs

Indications