Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as GSK3228836
Bepirovirsen · 13 trials · 3 indications
The number of participants who achieved FC after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication will be reported. The FC for HBV is defined as Sustained suppression (24 weeks or longer) of HBV DNA \< Lower limit of quantification (LLOQ) off all HBV treatment and HBsAg not detected with or without HBsAb after a finite duration of therapy.
HBV virologic response defined as HBV surface antigen (HBsAg) not detected and HBV deoxyribonucleic acid (DNA) less than (\<) lower limit of quantification (LLOQ).
An AE is any untoward medical occurrence (an unfavourable/unintended sign - including an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical study participant that is temporally associated with the study intervention. A grade 3 AE is an AE which prevents normal, everyday activities (in adults, such an AE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy).
An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or is an abnormal pregnancy outcome.
AESI related to GSK3228836 treatment include thrombocytopenia, alanine transaminase (ALT) increases, vascular inflammation and complement activation, renal injury or injection site reactions. AESI related to GSK3528869A include liver disease-related (LDR) AEs, hematological AESI or potential immune-mediated diseases (pIMDs). A grade 3 AE is an AE which prevents normal, everyday activities (in adults, such an AE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy).
SVR is defined as Hepatitis B surface antigen (HBsAg) below (\<) lower limit of quantification (LLOQ) and HBV deoxyribose nucleic acid (DNA) \< LLOQ. Rescue medication is defined as any medication initiated for the purpose of antiviral suppression other than the background stable NA therapy irrespective of the reason.
NA indicates nucleos(t)ide analogue (NA).
Sustained virologic response is defined as undetectable levels of Hepatitis B surface antigen (HBsAg) and Hepatitis-B virus deoxy-ribonucleic acid (HBV DNA) on treatment. The SVR was a composite endpoint defined as HBsAg and HBV DNA levels were less than (\<) Lower limit of quantitation (LLOQ) at the planned end of sequential treatment of GSK3228836 and PegIFN treatment which is sustained for 24 weeks post-GSK3228836 and PegIFN treatment in the absence of any rescue medication. Percentage values are rounded-off.
Sustained virologic response is defined as undetectable levels of Hepatitis B surface antigen (HBsAg) and Hepatitis-B virus deoxy-ribonucleic acid (HBV DNA) on treatment. The SVR was a composite endpoint defined as HBsAg and HBV DNA levels were less than (\<) Lower limit of quantitation (LLOQ) at the planned end of sequential treatment of GSK3228836 and PegIFN treatment which is sustained for 24 weeks post-GSK3228836 and PegIFN treatment in the absence of any rescue medication. Percentage values are rounded-off.
Percentage of participants achieving serum HBsAg level \<LLOQ were reported. Percentage values are rounded-off.
The SVR was a composite endpoint defined as Hepatitis B surface antigen (HBsAg) and Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) levels were less than (\<) Lower limit of quantitation (LLOQ) at the planned end of GSK3228836 treatment which is sustained for 24 weeks post-GSK3228836 treatment in the absence of rescue medication.
Continuous 12-lead electrocardiogram (ECG) was captured by Holter monitor. QTcF was measured from 10 digital ECGs extracted from the continuous tracing after 10 minutes of rest in supine position. Baseline was defined as pre-dose value on Day 1. Change from Baseline (CFB) was calculated by subtracting post-dose visit value from Baseline value. Geometric mean and 90 percent (%) Confidence Interval (CI) of predicted CFB QTcF adjusted for placebo at Cmax following supratherapeutic single doses of Bepirovirsen was presented using concentration QTc (C-QTc) analysis using exposure-response modelling. This approach utilized pre-specified linear mixed effects model where CFB QTcF was dependent variable. Fixed-effect parameters included intercept, slope, influence of Baseline on intercept, treatment and nominal time from first dose. Participant was included as additive random effect on both intercept and slope terms.
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of Bepirovirsen. Cmax calculation for this outcome measure is based on changes in model specifications and inclusion of different arms for respective outcome measures. Model includes Randomized Groups (Groups compared), injection site (arm, thigh and abdomen) as categorical covariates and log transformed Baseline weight as continuous covariate. The treatment is a factor in the model and position of a treatment as either test or reference would affect the Cmax values for a particular outcome measure due to differences in how the model accounts for variability and compares group for mean calculation. Pharmacokinetic (PK) Parameter Population included all participants in the PK concentration Population for whom valid and evaluable plasma PK parameters were derived.
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of Bepirovirsen. Blood samples were collected at indicated timepoints for PK analysis of Bepirovirsen. AUC(0-inf) calculation for this outcome measure is based on changes in model specifications and inclusion of different arms for respective outcome measures. Model includes Randomized Groups (Groups compared), injection site (arm, thigh and abdomen) as categorical covariates and log transformed Baseline weight as continuous covariate. The treatment is a factor in the model and position of a treatment as either test or reference would affect the AUC(0-inf) values for a particular outcome measure due to differences in how the model accounts for variability and compares group for mean calculation.
| Arm | Type | Description |
|---|---|---|
| Bepirovirsen | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Participants receiving Bepirovirsen | EXPERIMENTAL | Participants will receive bepirovirsen. |
| Participants receiving Placebo | PLACEBO_COMPARATOR | Participants will receive placebo. |
| ASO24-TI Group | EXPERIMENTAL | Eligible participants receive GSK3228836 (Treatment 1) study intervention for 24 weeks of Treatment 1 period, followed by GSK3528869A (Treatment 2) study intervention administered at Days 1, 57, 113 and 169 of Treatment 2 period. The interval between Treatment 1 and Treatment 2 is preferably 1 week, with the possibility to extend up to 12 weeks. |
| ASO24 Group | ACTIVE_COMPARATOR | Eligible participants receive GSK3228836 (Treatment 1) study intervention for 24 weeks of Treatment 1 period, followed by non-active control (Treatment 2) study intervention administered at Days 1, 57, 113 and 169 of Treatment 2 period. The interval between Treatment 1 and Treatment 2 is preferably 1 week, with the possibility to extend up to 12 weeks. |
| ASO12-TI Group | EXPERIMENTAL | Eligible participants receive GSK3228836 (Treatment 1) study intervention for 12 weeks of Treatment 1 period, followed by GSK3528869A (Treatment 2) study intervention administered at Days 1, 57, 113 and 169 of Treatment 2 period. The interval between Treatment 1 and Treatment 2 is preferably 1 week, with the possibility to extend up to 12 weeks. |
| ASO12 Group | ACTIVE_COMPARATOR | Eligible participants receive GSK3228836 (Treatment 1) study intervention for 12 weeks of Treatment 1 period, followed by non-active control (Treatment 2) study intervention administered at Days 1, 57, 113 and 169 of Treatment 2 period. The interval between Treatment 1 and Treatment 2 is preferably 1 week, with the possibility to extend up to 12 weeks. |
| Not-on-NA participants | EXPERIMENTAL | 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. |
| On-NA participants | EXPERIMENTAL | 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. |
| NA-cessated participants | EXPERIMENTAL | 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. |
| GSK3228836 300 mg (24 weeks) + PegIFN 180 mcg (24 weeks) | EXPERIMENTAL | Participants on stable NA therapy received 300 milligrams per week (mg/week) GSK3228836 for 24 weeks (plus a loading dose on Day 4 and 11), followed by Pegylated Interferon (PegIFN) 180 microgram per week (mcg/week) up to 24 weeks. |
| GSK3228836 300 mg (12 weeks) + PegIFN 180 mcg (24 weeks) | EXPERIMENTAL | Participants on stable NA therapy received 300mg/week GSK3228836 for 12 weeks (plus a loading dose on Day 4 and 11), followed by PegIFN 180 mcg/week up to 24 weeks. |
| GSK3228836 300 mg | EXPERIMENTAL | Participants on stable nucleos(t)ide therapy will receive GSK3228836 300 mg subcutaneously (SC) weekly once for 12 weeks along with a loading dose of GSK3228836 300 mg in Week 1 (Day 4) and Week 2 (Day 11). |
| Cohort 1: GSK3228836 300 mg + LD | EXPERIMENTAL | Eligible participants on stable nucleos(t)ide treatment will receive 300 milligrams (mg) GSK3228836 once weekly for 24 weeks along with loading dose (LD) of 300 mg GSK3228836 on Day 4 and Day 11. |
| Cohort 1: GSK3228836 300 mg + LD/ GSK3228836 150 mg + Placebo | EXPERIMENTAL | Eligible participants on stable nucleos(t)ide treatment will receive 300 mg GSK3228836 once weekly for 12 weeks along with LD of 300 mg GSK3228836 on Day 4 and Day 11 followed by step-down in dose of 150 mg GSK3228836 once weekly for 12 weeks along with placebo to match to maintain participant blinding. |
| Cohort 1: GSK3228836 300 mg + LD/ Placebo | EXPERIMENTAL | Eligible participants on stable nucleos(t)ide treatment will receive 300 mg GSK3228836 once weekly for 12 weeks along with LD of 300 mg GSK3228836 on Day 4 and Day 11 followed by placebo once weekly for 12 weeks. |
| Cohort 1: Placebo/ GSK3228836 300 mg + Placebo LD | EXPERIMENTAL | Eligible participants on stable nucleos(t)ide treatment will receive placebo once weekly for 12 weeks followed by 300 mg GSK3228836 once weekly for 12 weeks along with placebo LD to match on Day 4 and Day 11. |
| Cohort 2: GSK3228836 300 mg + LD | EXPERIMENTAL | Eligible participants not currently on nucleos(t)ide therapy will receive 300 mg GSK3228836 once weekly for 24 weeks along with LD of 300 mg GSK3228836 on Day 4 and Day 11. |
| Cohort 2: GSK3228836 300 mg + LD/ GSK3228836 150 mg + Placebo | EXPERIMENTAL | Eligible participants not currently on nucleos(t)ide therapy will receive 300 mg GSK3228836 once weekly for 12 weeks along with LD of 300 mg GSK3228836 on Day 4 and Day 11 followed by step-down in dose of 150 mg GSK3228836 once weekly for 12 weeks along with placebo to match to maintain participant blinding. |
| Cohort 2: GSK3228836 300 mg + LD/ Placebo | EXPERIMENTAL | Eligible participants not currently on nucleos(t)ide therapy will receive 300 mg GSK3228836 once weekly for 12 weeks along with LD of 300 mg GSK3228836 on Day 4 and Day 11 followed by placebo once weekly for 12 weeks. |
| Cohort 2: Placebo/ GSK3228836 300 mg + Placebo LD | EXPERIMENTAL | Eligible participants not currently on nucleos(t)ide therapy will receive placebo once weekly for 12 weeks followed by 300 mg GSK3228836 once weekly for 12 weeks along with placebo LD to match on Day 4 and Day 11. |
| Group 1 | EXPERIMENTAL | Bepirovirsen will be administered from a vial. |
| Group 2 | EXPERIMENTAL | Bepirovirsen will be administered from an autoinjector. |
| Group 1- Severe Renal Impairment Participants | EXPERIMENTAL | Participants with severe renal impairment will receive Bepirovirsen. |
| Group 2- Moderate Renal Impairment Participants | EXPERIMENTAL | Participants with moderate renal impairment will receive Bepirovirsen. |
| Group 3-Healthy Control Participants | EXPERIMENTAL | Healthy control participants will receive Bepirovirsen. |
| Bepirovirsen: Four-Dose SC Injection | ACTIVE_COMPARATOR | Participant received four subcutaneous (SC) injections of Bepirovirsen dose level 1 on Day 1. |
| Placebo: Four SC Injections | PLACEBO_COMPARATOR | Participants received four matching placebo SC injections on Day 1. |
| Bepirovirsen: Three-Dose SC Injection | ACTIVE_COMPARATOR | Participant received three SC injections of Bepirovirsen dose level 1 on Day 1. |
| Placebo: Three SC Injections | PLACEBO_COMPARATOR | Participants received three matching placebo SC injections on Day 1. |
| Bepirovirsen Vial by HCP | EXPERIMENTAL | Participants will receive Bepirovirsen vial administered by Healthcare Professionals (HCP). |
| Bepirovirsen PFS SSD by HCP | EXPERIMENTAL | Participants will receive Bepirovirsen PFS SSD administered by HCP. |
| Bepirovirsen PFS SSD self-administered post-training | EXPERIMENTAL | Participants will receive Bepirovirsen PFS SSD self- administered with training by HCP. |
| Bepirovirsen PFS SSD self-administered without training | EXPERIMENTAL | Participants will receive Bepirovirsen PFS SSD self- administered with no training by HCP. |
| Participants with Moderate (CP-B) hepatic impairment | EXPERIMENTAL | - |
| Participants with Mild (CP-A) hepatic impairment | EXPERIMENTAL | - |
| Healthy participants | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Bepirovirsen | DRUG | Bepirovirsen will be administered. |
| Placebo | OTHER | Matching placebo will be administered. |
| GSK3228836 | DRUG | 2 doses of GSK3228836 study intervention administered subcutaneously once per week for 12 weeks (Day 1 up to Day 78) to participants in ASO12-TI and ASO12 groups, or for 24 weeks (Day 1 up to Day 162) to participants in ASO24-TI and ASO24 groups, plus loading doses administered at Day 4 and Day 11 (2 doses each day) to participants in all groups during Treatment 1 period. |
| GSK3528869A | BIOLOGICAL | The GSK3528869A chronic Hepatitis B targeted immunotherapy (CHB-TI) consisting of 4 doses administered intramuscularly as follows: * 1 dose of the Chimpanzee adenovectored HBV vaccine (ChAd155-hIi-HBV) at Day 1 of Treatment 2 period. * 1 dose of the Modified Vaccinia Virus Ankara HBV vaccine (MVA-HBV) at Day 57 of Treatment 2 period. * 2 subsequent doses of the AS01B-4-adjuvanted HBc-HBs proteins (HBc-HBs/AS01B-4) administered at Day 113 and Day 169 of Treatment 2 period. |
| Control | DRUG | 4 doses of non-active control administered intramuscularly in the deltoid region of the non-dominant arm at Days 1, 57, 113 and 169 to participants in ASO24 and ASO12 control groups during Treatment 2 period. |
| PegIFN | DRUG | Participants will be administered PegIFN. |
| NA therapy | DRUG | Participants will continue to receive their NA therapy for the duration of the study. |
| Nucleos(t)ide therapy | DRUG | Participants receiving nucleos(t)ide therapy upon entry in the study will continue to receive nucleos(t)ide therapy for the duration of the study. |
Inclusion Criteria: * Participants who have documented chronic HBV infection ≥6 months prior to screening and currently receiving stable NA therapy defined as no changes to their NA regimen from at least 6 months prior to Screening and with no planned changes to the stable regimen over the duration...
Bepirovirsen is an investigational RNA therapy being developed by GSK plc for chronic hepatitis B and hepatitis B. It is an antisense oligonucleotide designed to target hepatitis B virus (HBV). It is currently in Phase 3 clinical development and has not been established as an approved treatment.
Bepirovirsen targets hepatitis B virus (HBV). It is an antisense oligonucleotide, a class of RNA therapy that binds viral RNA, and its molecular target is HBV. This mechanism underlies its investigation as a treatment for chronic hepatitis B infection.
Bepirovirsen is developed by GSK plc, which trades under the ticker GSK. GSK is running the clinical development program for the drug across Phase 1, Phase 2, and Phase 3 studies in hepatitis B and chronic hepatitis B.
Bepirovirsen is in Phase 3 clinical development for chronic hepatitis B. It is investigational and is being studied in randomized, double-blind, placebo-controlled trials. Six trials in total have been registered, with four currently active and two completed.
Registered bepirovirsen trials include NCT06497504, a Phase 2 study in people with HIV and chronic hepatitis B (B-Focus), and Phase 1 studies NCT07905157, NCT07168356, and NCT06422767. NCT06422767, which assessed cardiac conduction in healthy volunteers, is completed. Across these trials, total enrollment is 1,838 participants.
Bepirovirsen is being developed for the treatment of chronic hepatitis B and hepatitis B. It is an investigational antisense oligonucleotide targeting HBV and is in Phase 3 development. Its safety and efficacy in chronic hepatitis B are being evaluated in randomized, placebo-controlled clinical trials.