Phase IIb study of GSK3228836 in Chronic Hepatitis B Participants
Research type
Research Study
Full title
Phase IIb Multi-Center, Randomised, Partial-Blind Parallel Cohort Study to Assess the Efficacy and Safety of Treatment with GSK3228836 in Participants with Chronic Hepatitis B Virus (B-Clear)
IRAS ID
282923
Contact name
Stephen Ryder
Contact email
Sponsor organisation
GlaxoSmithKline
Eudract number
2020-001083-29
Duration of Study in the UK
2 years, 0 months, 2 days
Research summary
Research Summary
GSK3228836 is an experimental medicine being developed for the treatment of Chronic Hepatitis B (CHB) caused by the hepatitis B virus (HBV), which infects the liver and can cause liver damage. Medicines are available, but they only stop the virus from multiplying and the body is not able to fully control the infection, so patients have to keep taking medicines.
This research study is being done to learn more about CHB and if GSK3228836 can improve the treatment of CHB. GSK3228836 has been given to participants with CHB for 4 weeks in a previous study which showed a decrease in viral substances (e.g. Hepatitis B surface antigen [HBsAg]). In this study, longer treatment periods will be tested with GSK3228836 to see if this can improve the removal of viral substances from the body and prevent their return. Participants will be separated into two groups based on if they are taking nucleos(t)ide therapy (like tenofovir or entecavir) or not currently taking nucleos(t)ide therapy to understand if one group responds better to treatment than the other. In each group, participants will be randomly put into one of four treatment arms with different doses.
At least 440 patients will be treated with GSK3228836 in this study worldwide, with about 15 expected to be from UK hospitals.Participants will begin treatment after confirming eligibility. Participants will attend treatment visits every week for 24 weeks (plus 2 extra visits per week within the first 2 weeks) and will receive 2 injections at each visit. After the participant completes treatment, they will attend 8 follow up visits over 24 weeks. Most participants will be in the study for approximately 55 weeks.
Tests and procedures will include (but not limited to): blood tests, physical examinations, vital signs, pregnancy tests, electrocardiograms (ECGs) and questionnaire completion.
Summary of Results
24-week treatment with bepirovirsen 300 mg induced sustained loss of HBsAg and HBV DNA for 24 weeks after treatment end in both participants on stable nucleos(t)ide (NA) therapy and those not on NA therapy.
Response may be predicted by baseline patient characteristics, specifically low baseline HBsAg levels.
The safety profile in both On-NA and Not-on-NA cohorts was similar. In both the On-NA and Not-on-NA populations, the 24-week dosing regimen of 300 mg per week had a comparable safety profile and tolerability compared with the other bepirovirsen regimens investigated. The majority of Adverse Events were reported within the adverse events of special interest, which have been previously described for other 2’MOE ASOs. No new safety signals were identified that would preclude further development.REC name
East Midlands - Derby Research Ethics Committee
REC reference
20/EM/0142
Date of REC Opinion
16 Jul 2020
REC opinion
Further Information Favourable Opinion