Chronic Hepatitis B infection MedDRA version: 20.1 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age 1.At least 18 years of age at the time of signing the informed consent (if country/site age requirements for consent differ, the more stringent [e.g., higher age] restriction will be required for that country/site). Type of Participant and Disease Characteristics 2.Participants must be HBeAg negative at screening. 3.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 of the study 4.Plasma or serum HBsAg concentration >100 IU/mL, but no greater than 3000 IU/mL 5.Plasma or serum HBV DNA concentration 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 80
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1.Clinically significant abnormalities, aside from chronic HBV infection in medical history (e.g., moderate severe liver disease other than chronic HBV, acute coronary syndrome within 6 months of screening, major surgery within 3 months of screening, significant/unstable cardiac disease, uncontrolled diabetes, bleeding diathesis or coagulopathy) or physical examination 2.Co-infection with: a.Current history of Hepatitis C infection or participants that have been cured for 2 and FibroSure/FibroTest result >0.7 •If only 1 parameter (APRI or FibroSure/FibroTest) result is positive, a discussion with the Medical Monitor is required before inclusion in study is permitted b.Regardless of APRI of Fibrosure/FibroTest score, if the participant meets 1 of the following criteria documented from their medical history, they will be excluded from the study •Liver biopsy (i.e., Metavir Score F4) •Liver stiffness >12 kPa 4.Diagnosed or suspected hepatocellular carcinoma as evidenced by the following a.Alpha-fetoprotein concentration =200 ng/mL b.If the screening alpha fetoprotein concentration is =50 ng/mL and <200 ng/mL, the absence of liver mass must be documented by imaging within 6 months before randomization 5.History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer). Participants under evaluation for possible malignancy are not eligible. 6.History of vasculitis or presence of symptoms and signs of potential vasculitis (e.g., vasculitic rash, skin ulceration, repeated blood detected in urine without identified cause) or history/presence of other diseases that may be associated with vasculitis condition (e.g., systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex) 7.History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension) 8.History of alcohol or drug abuse/dependence a.Current alcohol use as judged by investigator to potentially interfere with participant compliance b.History of or current drug abuse/dependence as judged by the investigator to potentially interfere with participant compliance i.Refers to illicit drugs and substances with abuse potential. Medications that are used by the participant as directed, whether over-the-counter or through prescription, are acceptable and would not meet the exclusion criteria Prior/Concomitant Therapy 9.Currently taking, or took within 3 months of screening, any immunosuppressing drugs (e.g., prednisone), other than a short course of therapy (=2 weeks) or topical/inhaled steroid use. 10.Participants to whom immnosuppressive treatment, including therapeutic doses of steroids is contraindicated, should not be considered for enrolment in the study. 11.Currently taking, or HAS TAKEN within 12 months of Screening, any interferon containing therapy. 12.Participants requiring anti-coagulation therapies (e.g., warfarin, Factor Xa inhibitors) or anti-platelet agents (like clopidogrel or aspirin) unless treatment can safely be discontinued throughout dura
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy: To assess the treatment effect of 24 weeks bepirovirsen with loading doses to achieve functional cure in HBeAg-negative participants with chronic HBV infection on-NA treatment with baseline HBsAg =1000 IU/mL;Secondary Objective: Efficacy: To assess the treatment effect of 24 weeks bepirovirsen with loading doses to achieve functional cure in HBeAg-negative participants with chronic HBV infection on NA treatment with baseline HBsAg =3000 IU/mL Efficacy: To assess the treatment effect of 24 weeks bepirovirsen with loading doses in HBV DNA suppression off-treatment after a finite duration of therapy in HBeAg-negative participants with chronic HBV infection on NA treatment with baseline HBsAg =1000 IU/mL Efficacy: To assess the treatment effect of 24 weeks bepirovirsen with loading doses in HBV DNA suppression after a finite duration of therapy in HBeAg-negative participants with chronic HBV infection on NA treatment with baseline HBsAg =3000 IU/mL Safety: To assess the safety and tolerability of bepirovirsen when dosed for 24 weeks duration with loading doses in HBeAg-negative participants with chronic HBV infection on NA treatment;Primary end point(s): Functional cure for 24 weeks after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication in participants with baseline HBsAg <1000IU/mL;Timepoint(s) of evaluation of this end point: Week 72 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Functional cure for 24 weeks after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication in participants with baseline HBsAg <3000IU/mL - Sustained suppression of HBV DNA (<LLOQ) for 24 weeks after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication in participants with baseline HBsAg <1000IU/mL - Sustained suppression of HBV DNA (<LLOQ) for 24 weeks after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication in participants with baseline HBsAg <3000 IU/mL;Timepoint(s) of evaluation of this end point: Week 72 | — |
Countries
Argentina, Brazil, Bulgaria, Canada, China, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Japan, Korea, Republic of, Mexico, Panama, Poland, Romania, Singapore, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials Help Desk
GlaxoSmithKline Research & development Ltd
Outcome results
None listed