Long-Term Follow-Up for GSK3228836 in Hepatitis B
(B-Sure Trial)
Recruiting in Palo Alto (17 mi)
+67 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: GlaxoSmithKline
Must be taking: Nucleos(t)ide analogues
Disqualifiers: Other HBV studies, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This trial is checking the duration of benefits for people who previously took the medication GSK3228836 and showed improvement. No new treatment will be given during this study.
Will I have to stop taking my current medications?
If you are currently on a stable nucleos(t)ide analogue (NA) treatment, you will need to stop taking it according to the study's cessation schedule. If you are not on NA treatment, you do not need to stop any current medications.
What data supports the effectiveness of the drug GSK3228836 (Bepirovirsen) in treating chronic hepatitis B?
Eligibility Criteria
This trial is for people who have had Hepatitis B and were previously treated with GSK3228836, achieving full or partial virus control. They must be able to stop their current antiviral meds as per the study's schedule and give informed consent. Those in other HBV studies or with conditions that make participation risky can't join.Inclusion Criteria
I've had a successful treatment with GSK3228836 for hepatitis B.
I am able to understand and sign the consent form.
I have had GSK3228836 before and it partially worked for me.
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Exclusion Criteria
Participants who have/or are currently participating in another non-GSK interventional clinical study exploring HBV treatment since completing their treatment with GSK3228836
Any condition which, in the opinion of the investigator or Medical Monitor, contraindicates their participation in this study
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Follow-up
Participants are monitored for durability of treatment response from the parent study
33 months
Extended Follow-up
Participants maintaining functional cure or partial response are followed up for an additional 2 years
24 months
Treatment Details
Interventions
- GSK3228836 (Virus Therapy)
Trial OverviewThe study isn't testing a new treatment; instead, it's checking how long the effects of GSK3228836 last in patients who've already taken it. It looks at whether they maintain low levels of hepatitis B surface antigen (HBsAg) and DNA without further doses.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: On-NA participantsExperimental Treatment2 Interventions
Participants rolling over from studies 209668, 209348, 212602, 202009, 219288, and 217023 who entered the parent study on stable NA therapy and remained on NA therapy for the duration of the treatment and follow-up periods in the parent study will be included in this arm. NA cessation will occur at 3 months in 206882 for eligible and willing participants. Participants will be followed up for 33 months. Participants rolling over from studies 209668 and 209348 who stopped NA treatment and are maintaining either FC or a partial response at Month 33, and remaining off NA treatment, will be eligible to be followed up for an additional 2 years. No study treatment will be administered in this study.
Group II: Not-on-NA participantsExperimental Treatment2 Interventions
Participants rolling over from study 209668 who have not received nucleos(t)ide analogue (NA) therapy during the parent study and remain off NAs will be included in this arm. Participants will be followed up for 33 months. Participants maintaining either functional cure (FC) or a partial response off NA treatment at Month 33 will be eligible to be followed up for an additional 2 years. No study treatment will be administered in this study.
Group III: NA-cessated participantsExperimental Treatment2 Interventions
Participants rolling over from studies 202009 and 219288 who have stopped NA treatment during the parent study will be included in this arm. Participants will be followed up for 33 months. No study treatment will be administered in this study.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
GSK Investigational SiteToronto, Canada
GSK Investigational SiteSacramento, CA
GSK Investigational SiteBoston, MA
GSK Investigational SiteCalgary, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
GlaxoSmithKlineLead Sponsor
References
B-Clear Phase 2b Study Design: Establishing the Efficacy and Safety of Bepirovirsen in Patients with Chronic Hepatitis B Virus Infection. [2023]Bepirovirsen (GSK3228836) is an antisense oligonucleotide that induced rapid and prolonged hepatitis B surface antigen (HBsAg) reduction with a favorable safety profile following 4 weeks of treatment in participants with chronic hepatitis B virus (HBV) infection. The objective of the phase 2b study B-Clear is to access the efficacy and safety of bepirovirsen in participants with chronic HBV infection.
Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. [2023]Bepirovirsen is an antisense oligonucleotide that targets all hepatitis B virus (HBV) messenger RNAs and acts to decrease levels of viral proteins.
Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy. [2023]Bepirovirsen, an antisense oligonucleotide targeting pregenomic and mRNA transcripts of HBV, has been conjugated to N-acetyl galactosamine (GSK3389404) to enhance hepatocyte delivery. This dose-finding study was the first to assess GSK3389404 for chronic HBV infection.
Safety, tolerability and antiviral activity of the antisense oligonucleotide bepirovirsen in patients with chronic hepatitis B: a phase 2 randomized controlled trial. [2022]Chronic infection with hepatitis B virus (HBV) leads to an increased risk of death from cirrhosis and hepatocellular carcinoma. Functional cure rates are low with current treatment options (nucleos(t)ide analogs (NAs) and pegylated interferons). Bepirovirsen is an antisense oligonucleotide targeting all HBV messenger RNAs; in cell culture and animal models, bepirovirsen leads to reductions in HBV-derived RNAs, HBV DNA and viral proteins. This phase 2 double-blinded, randomized, placebo-controlled trial is the first evaluation of the safety and activity of an antisense oligonucleotide targeting HBV RNA in both treatment-naïve and virally suppressed individuals with chronic HBV infection. The primary objective was to assess the safety and tolerability of bepirovirsen in individuals with chronic hepatitis B (CHB) (NCT02981602). The secondary objective was to assess antiviral activity, including the change from baseline to day 29 in serum hepatitis B surface antigen (HBsAg) concentration. Participants with CHB infection ≥6 months and serum HBsAg ≥50 IU ml-1 were enrolled from seven centers across Hong Kong and the Republic of Korea and randomized (3:1 within each dose cohort) to receive bepirovirsen or placebo via subcutaneous injection twice weekly during weeks 1 and 2 (days 1, 4, 8 and 11) and once weekly during weeks 3 and 4 (days 15 and 22). Participants were then followed for 26 weeks. Twenty-four participants were treatment-naïve and seven were receiving stable NA therapy. Treatment-emergent adverse events were mostly mild/moderate (most commonly injection site reactions). Eleven (61.1%) and three (50.0%) treatment-naïve participants experienced one or more treatment-emergent adverse event in the bepirovirsen and placebo groups, respectively. In participants receiving NA therapy, the corresponding numbers were three (60.0%) and one (50.0%). Transient, self-resolving alanine aminotransferase flares (≥2× upper limit of normal) were observed in eight treatment-naïve participants and three participants on stable NA regimens in the bepirovirsen treatment arms. HBsAg reductions were observed and were significant versus placebo for treatment-naïve participants receiving bepirovirsen 300 mg (P = 0.001), but not for the bepirovirsen 150 mg group (P = 0.245) or participants receiving stable NA therapy (P = 0.762). Two participants in each of the 300 mg dose groups achieved HBsAg levels below the lower limit of quantitation by day 29 (n = 3) or day 36 (n = 1). Bepirovirsen had a favorable safety profile. These preliminary observations warrant further investigation of the safety and activity of bepirovirsen in a larger CHB patient population.
Progress in the treatment of chronic hepatitis B: long-term experience with adefovir dipivoxil. [2013]Most chronic hepatitis B patients do not undergo a curative response to interferon-alpha or nucleoside/nucleotide-based regimens and require long-term therapy. Long-term safety, efficacy and resistance profiles of hepatitis B virus (HBV) drugs are therefore crucial issues for patient management. Adefovir dipivoxil is a nucleotide prodrug indicated for the treatment of patients with hepatitis B e antigen positive or hepatitis B e antigen negative chronic hepatitis B, lamivudine-resistant HBV infection, HBV infection pre- or post-liver transplantation, or HlV co-infection. Long-term data from clinical trials of up to 5 years duration of adefovir dipivoxil have recently become available and are reviewed here. These data demonstrate that adefovir dipivoxil therapy results in sustained efficacy and safety in the majority of patients after multiple years of treatment. The efficacy of adefovir dipivoxil in treating lamivudine-resistant HBV and the delayed emergence of adefovir resistance are key factors contributing to the durable response achieved in broad groups of chronic hepatitis B patients.