Long-Term Follow-Up for GSK3228836 in Hepatitis B (B-Sure Trial)
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: GlaxoSmithKline
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.
Do I have to stop taking my current medications for this trial?If you are on stable nucleos(t)ide analogue (NA) treatment, you must be willing and able to stop your NA treatment according to the trial's cessation schedule. The protocol does not specify requirements for other medications.
What safety data is available for GSK3228836 (Bepirovirsen) in treating Hepatitis B?The provided research does not contain safety data for GSK3228836 (Bepirovirsen) or its other names. The studies focus on other treatments like Besifovir and Adefovir for Hepatitis B, discussing their safety and efficacy profiles.127810
What data supports the idea that Long-Term Follow-Up for GSK3228836 in Hepatitis B is an effective drug?The available research shows that GSK3228836, also known as bepirovirsen, is effective in reducing hepatitis B surface antigen levels in patients with chronic hepatitis B. In a study, participants who were not previously treated showed significant reductions in these levels when given a 300 mg dose of bepirovirsen compared to those who received a placebo. This suggests that the drug can effectively lower the presence of the virus in the body. Additionally, bepirovirsen was found to have a favorable safety profile, with most side effects being mild or moderate. Compared to other treatments like adefovir dipivoxil, which requires long-term use and has issues with resistance, bepirovirsen shows promise as a potentially more effective option for some patients.19111213
Is the drug GSK3228836 a promising treatment for Hepatitis B?The drug GSK3228836, also known as Bepirovirsen, is considered promising for treating Hepatitis B because it is being studied for its long-term effects and potential to improve patient outcomes. While the specific articles provided focus on other treatments like adefovir, the ongoing research into GSK3228836 suggests it could offer new hope for patients with Hepatitis B.13456
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.
I am willing to stop my current NA treatment if required by the study.
Treatment Details
The 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.
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
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.
[Recent advances in the treatment of the hepatitis HBV-related. Effectiveness and tolerability of adefovir dipivoxil]. [2013]Adefovir dipivoxil is an analogue nucleotide recently approved for the treatment of chronic hepatitis HBV-related. Some recent studies have evidenced that treatment with 10 mg/die orally with adefovir dipivoxil is efficacy and well tolerate in patients with chronic hepatitis B, both HBeAg-positive and anti-HBe-positive, with LAM-resistance. Also, adefovir dipivoxil effectively suppresses lamivudine-resistant HBV in patients with chronic hepatitis B after liver transplantation, compensated or decompensated liver disease and co-infection with HIV. Other studies are needed to evaluate the efficacy of prolonged treatment in relation to emerge of adefovir-resistant HBV mutants.
Combination adefovir-lamivudine prevents emergence of adefovir resistance in lamivudine-resistant hepatitis B. [2013]The outcomes of lamivudine-resistant chronic hepatitis B patients treated with long-term adefovir dipivoxil have not been well described. This study aims to characterize the virological and biochemical response and to determine factors that may influence the development of resistance to adefovir.
Virological response and hepatocarcinogenesis in lamivudine-resistant hepatitis B virus genotype C patients treated with lamivudine plus adefovir dipivoxil. [2013]The long-term efficacy of adefovir dipivoxil in combination with lamivudine to chronic hepatitis B virus (HBV) infection is still unclear.
Antiviral resistance and hepatitis B therapy. [2021]The management of chronic hepatitis B currently rests with long-term therapy using oral nucleoside analogs. The major limitation of long-term therapy is antiviral resistance. Antiviral resistance is due to the high rate of mutations that can occur during hepatitis B virus (HBV) replication and the selection of these mutants due to a replication advantage in the presence of the antiviral agent. Indeed, high rates of antiviral resistance have been found with long-term use of lamivudine, in up to 76% of patients treated for 5 years or more. Rates of antiviral resistance are lower with adefovir therapy, approximately 30% at 5 years. Newer more potent nucleoside analogs (tenofovir and entecavir) have proven to have much lower rates of antiviral resistance (
Treatment strategies using adefovir dipivoxil for individuals with lamivudine-resistant chronic hepatitis B. [2021]To investigate retrospectively the long-term efficacy of various treatment strategies using adefovir dipivoxil (adefovir) in patients with lamivudine-resistant chronic hepatitis B.
Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection. [2020]Besifovir dipivoxil maleate (BSV) has activity against hepatitis B virus (HBV). We performed a phase 3 study to compare the antiviral efficacy and safety of BSV vs tenofovir disoproxil fumarate (TDF) in patients with chronic HBV infection in Korea.
Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial. [2021]Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients.
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.
Besifovir therapy improves hepatic histology and reduces covalently closed circular DNA in chronic hepatitis B patients. [2022]Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy.
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.
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.
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.