Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK3228836 · 5 trials · 2 indications
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.
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.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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. |
| Participants with Moderate (CP-B) hepatic impairment | EXPERIMENTAL | - |
| Participants with Mild (CP-A) hepatic impairment | EXPERIMENTAL | - |
| Healthy participants | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| 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. |
| Placebo | DRUG | Placebo will be available as a clear colorless solution for injection to be administered subcutaneously once weekly. |
Inclusion criteria: * Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol. * Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study-specific procedure. * A male or female betwee...
GSK3228836 is an investigational small molecule being developed for the treatment of chronic hepatitis B. It is currently in Phase 2 clinical development and has been studied in multiple trials enrolling over 600 participants with chronic hepatitis B.
GSK3228836 is being developed by GSK plc, a global biopharmaceutical company. GSK plc trades on the London Stock Exchange and as an American Depositary Receipt under the ticker GSK on the New York Stock Exchange.
GSK3228836 is in Phase 2 clinical development for chronic hepatitis B. It is an investigational drug, meaning it has not been approved by regulatory authorities. Four clinical trials have been completed, including Phase 1 and Phase 2 studies.
GSK3228836 has been studied in four completed clinical trials. The largest, NCT04449029, enrolled 457 participants with chronic hepatitis B. Other trials include NCT04544956, a mechanistic study with 12 participants, NCT04676724, a sequential treatment study with 108 participants, and NCT04971928, a pharmacokinetic study in 24 participants.
GSK3228836 is also known as bepirovirsen. It is an investigational antisense oligonucleotide being developed by GSK plc for the treatment of chronic hepatitis B. The drug has been evaluated in Phase 2 clinical trials, including studies combining it with peginterferon.