Hepatitis B virus (HBV) infection MedDRA version: 20.0 Level: PT Classification code 10019731 Term: Hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: GSK3228836
Product Code: [GSK3228836]
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Bepirovirsen
CAS Number: 1403787-62-1
Current Sponsor code: GSK3228836A
Concentrati
Sponsors
GLAXOSMITHKLINE BIOLOGICALS
Eligibility
Sex/Gender
All
Inclusion criteria
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 between, and including, 18 and 65 years of age at the time of signing of the informed consent. • Participants who are Hepatitis B envelop antigen (HBeAg) positive or negative. • Participants who have documented chronic HBV infection =6 months prior to screening and currently receiving stable NA therapy population defined as no changes to their nucleos(t)ide regimen from at least 6 months prior to screening and with no planned changes to the stable regimen over the duration of the study. • CHB patient, under and adherent to treatment with a NA with high barrier to resistance (e.g. entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide). • Participants with ALT = 2x upper limit of normal (ULN) documented in last 6 months. • Participants with plasma or serum HBsAg concentration >100 IU/mL. • Participants must be adequately suppressed, defined as plasma or serum HBV DNA =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: •Clinically significant abnormalities, aside from chronic HBV infection in medical history or physical examination •Co-infection with: Current or past history of HCV, HIV, HDV •History of or suspected liver cirrhosis and/or evidence of cirrhosis •FibroScan TE score >9.6 kPa and FibroTest score >0.59 at Screening •Diagnosed or suspected HCC •History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection •History of vasculitis or presence of symptoms and signs of potential vasculitis •History of extrahepatic disorders possibly related to HBV immune conditions •Positive (or borderline positive) ANCA at screening •Low C3/C4 at screening AND evidence of past history or current manifestations of vasculitic/inflammatory/autoimmune conditions •History of alcohol or drug abuse/dependence •QTcF =450 msec •Laboratory results as follows: -Serum albumin1.25 -PLT count1.25xULN unless it is considered as clinically not significant by the Investigator -ACR=0.03 mg/mg •Medical history of hepatic decompensation •Planned for liver transplantation or previous liver transplantation •Documented evidence of other currently active cause of hepatitis •Any other clinical condition that might pose additional risk to the participant due to participation in the study •Major congenital defects •Recurrent history or uncontrolled neurological disorders or seizures •History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s) •Use of any investigational or non-registered product other than the study interventions during the period beginning 30 days before the first dose of study interventions, or their planned use during the study •Use of systemic cytotoxic agents, chronic antiviral agents or Chinese herbal medicines which may have activity against HBV within the previous 6 months (M) prior the study •Currently taking, or took within 12 M of screening, any interferon-containing therapy •Administration of adenovirus/adenovector-based or MVA-based vaccine within the last 12 M, except for adenovirus/adenovector-based COVID-19 vaccines that could be administered up to 30 days prior to the first study vaccine dose •Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 14 days before the first dose and ending 30 days after the last dose of study intervention administration •Administration of long-acting immune-modifying drugs at any time during the study •Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 M before the first dose of study interventions or planned administration during the study •Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting 3 M prior to the first study intervention. Inhaled and topical steroids are allowed •Participants for whom immunosuppressive treatment is not advised •Treatment with nephrotoxic drugs or competitors of renal excretion within 2 M prior to Screening or planned during the study •Participants requiring anti-coagulation therapies •Concurrently participating in another clinical study •Previous participation in clinical trials with administration of either GSK3228836 or GSK3528869A •Previous participation in a clinical study in which he/she has received an investigational product •Prior treatme
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety • To assess the safety of sequential treatment with GSK3228836 and GSK3528869A in participants with CHB infection stable on NA therapy. Efficacy • To assess the efficacy of sequential treatment with GSK3228836 and GSK3528869A. • To assess the efficacy of sequential treatment with GSK3228836 and GSK3528869A in comparison with GSK3228836 treatment.;Secondary Objective: Safety • To assess the safety of sequential treatment with GSK3228836 and GSK3528869A in participants with CHB infection stable on NA therapy. Efficacy • To assess the efficacy of sequential treatment with GSK3228836 and GSK3528869A in comparison with baseline in participants with CHB infection who are virally suppressed on NA therapy. • To describe durability of Sustained Virologic Response (SVR) Immunogenicity • To assess the humoral and cellular immune responses specific to HBs and HBc antigens of sequential treatment with GSK3228836 and GSK3528869A in participants with CHB infection who are virally suppressed on NA therapy.;Primary end point(s): 1. Percentage of participants reporting any grade 3 adverse event (AE) from first dose of GSK3228836 up to study end 2. Percentage of participants reporting any serious adverse event (SAE) from first dose of GSK3228836 up to study end 3. Percentage of participants reporting any grade 3 adverse events of special interest (AESIs) from first dose of GSK3228836 up to study end 4. Percentage of participants who achieve sustained virologic response (SVR) for 24 weeks after end of active treatment in the absence of rescue medication, and difference between treatment arms (corresponding to GSK3228836 regimens);Timepoint(s) of evaluation of this end point: 1. From first dose of GSK3228836 (Treatment 1 [T1]-Day[D]1) up to study end (Treatment 2 [T2]-D841) 2, 3. From first dose of GSK3228836 (T1-D1) up to study end (T2-D841) 4. For up to 24 weeks after end of active treatment (end of active treatment = T1-D78 for ASO12 group, T1-D162 for ASO24 gr | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 Percentage (%) of participants reporting each solicited administration site event post-GSK3528869A study intervention administration 2 % of participants reporting each solicited systemic event post-GSK3528869A study intervention administration 3 % of participants reporting any unsolicited AE post-GSK3528869A study intervention administration 4 % of participants reporting any AE from first dose of GSK3228836 up to study end 5 % of participants reporting any AESIs from first dose of GSK3228836 up to study end 6 % of participants reporting any pIMDs from first dose of GSK3528869A up to study end 7 % of participants reporting hematological, biochemical or urinalysis laboratory abnormalities at pre-defined time points during T1 period 8 % of participants reporting hematological, biochemical or urinalysis laboratory abnormalities at pre-defined time points during T2 period 9 % of participants reporting hematological, biochemical or urinalysis laboratory abnormalities at pre-defined time points during follow-up period 10 % of participants who achieve quantitative Hepatitis B surface antigen assessment (qHBsAg) decrease & HBsAg loss at pre-defined time points from GSK3228836 baseline (T1-D1) up to end of treatment period 11 % of participants who achieve qHBsAg decrease & HBsAg loss at pre-defined time points from GSK3228836 baseline (T1-D1) up to end of T1 period 12 % of participants who achieve qHBsAg decrease & HBsAg loss at pre-defined time points from GSK3528869A/control baseline (T2-D1) up to end of T2 period 13 Changes in qHBsAg at pre-defined time points from GSK3228836 baseline (T1-D1) up to end of treatment period 14 Changes in qHBsAg at pre-defined time points from GSK3228836 baseline (T1-D1) up to end of T1 period 15 Changes in qHBsAg at pre-defined time points from GSK3528869A/control baseline (T2-D1) up to end of T2 period 16 % of participants in ASO24-TI & ASO24 groups with HBsAg loss & anti-HBs seroconversion 17 % of participants in | — |
Countries
Belgium, Bulgaria, France, Germany, Hong Kong, Italy, Korea, Republic of, Philippines, Poland, Romania, Russian Federation, Singapore, Spain, Taiwan, Thailand, Turkey, United Kingdom
Contacts
Public ContactClinical Disclosure Advisor
GlaxoSmithKline Biologicals
Outcome results
None listed