Chronic Hepatitis B 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: AGE 1.At least 18 to 75 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 who are eligible to be treated with PegIFN (Table 7) 3.Documented chronic HBV infection =6 months prior to screening AND currently receiving stable NA therapy except telbivudine, 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 5.Plasma or serum HBV DNA =65 years) yes F.1.3.1 Number of subjects for this age range 20
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, autoimmune disease, or coagulopathy) or physical examination 2.Co-infection with: a.Current or past history of Hepatitis C virus (HCV) b.Human immunodeficiency virus (HIV) c.Hepatitis D virus (HDV) 3.History of or suspected liver cirrhosis and/or evidence of cirrhosis as determined by a.Both Aspartate aminotransferase (AST)-Platelet Index (APRI) >2 and FibroSure/FibroTest result >0.7 within 12 months of screening i.If only one 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 or Fibrosure/FibroTest score, if the participant has historical evidence of one of the following criteria, they will be excluded from the study i.Liver biopsy (i.e., Metavir Score F4) ii. 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 randomisation 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, cryoglobulinaemia, uncontrolled hypertension) 8.Poorly controlled thyroid dysfunction or abnormal thyroid stimulating hormone (TSH) levels 9.Positive (or borderline positive) Anti-neutrophil cytoplasmic antibody (ANCA) at screening : a.Participants that meet these criteria may be considered for inclusion in the study following: i.Analysis of MPO-ANCA [perinuclear anti-neutrophil cytoplasmic antibodies (pANCA)] and PR3-ANCA [classical anti-neutrophil cytoplasmic antibodies (cANCA)] AND ii.A discussion with the Medical Monitor to review participant’s complete medical history to ensure no past history or current manifestations of a vasculitic/inflammatory/auto-immune condition 10.Low C3 at screening AND evidence of past history or current manifestations of vasculitic/inflammatory/auto-immune conditions a.All participants with low C3 at screening should have their medical history discussed with the Medical Monitor prior to enrolment 11.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 investiga
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The main Estimand supporting the primary objective is defined as: • Population: Participants with CHB on stable NA therapy who received at least one dose of GSK3228836 • Treatment: 300 mg GSK3228836 for 12 or 24 weeks followed by up to 24 weeks of PegIFN therapy while on stable NA therapy • Variable (Categorical): Participants achieving Sustained Virologic Response (SVR) (HBsAg <LLOQ and HBV DNA <LLOQ) for 24 weeks after the planned end of sequential treatment, without use of any rescue medication • Intercurrent Events: o Discontinuation of, interruption in, and nonadherence to GSK3228836 and PegIFN not related to any wide disruptive events (such as COVID-19 pandemic) will be ignored (treatment policy strategy). o Ineligibility to receive PegIFN will be ignored (treatment policy strategy) o Use of rescue medication (composite strategy). o Wide disruptive events (such as COVID-19 pandemic) leading to discontinuation of, interruption in, and non-adherence to GSK3228836 and PegIFN will be handled assuming they had not happened (hypothetical strategy). • Population Summary: The percentage of participants in each treatment group who achieve SVR, without use of any rescue medication The main primary estimand supporting the primary objective in participants with CHB on stable NA therapy in each treatment arm is the percentage of participants that achieve SVR (HBsAg <LLOQ and HBV DNA <LLOQ) for 24 weeks after the planned end of sequential treatment in the absence of rescue medication, regardless of ineligibility to receive PegIFN, discontinuation of, interruption in, and non-adherence to GSK3228836 and PegIFN, had they not been affected by wide disruptive events. Three supplementary Estimands are defined to support the primary objective: • The first supplementary Estimand is defined in the same way as the main Estimand, except the assessment time frame for patients achieving SVR will be 24 weeks after the actual end of treatment. Therefore, the strateg | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The Estimand supporting the objective is defined as: • Population: Participants with CHB on stable NA therapy who received at least one dose of GSK3228836; For the time to ALT normalisation variable, population will be aforementioned participants with baseline ALT >ULN. • Treatment: 300 mg GSK3228836 for 12, or 24 weeks followed by 24 weeks of PegIFN therapy while on stable NA therapy • Categorical Variables: o Achieving HBsAg ULN Population summary is the percentage of participants in each category for each treatment group. • Continuous Variables: o Actual values and change from baseline over time for HBsAg, HBV DNA and HBeAg o Actual values and change from baseline over time for HBs antibody (anti-HBsAg) and HBe antibody (anti-HBeAg) levels over time o Actual values and change from baseline over time for ALT Population summary is the mean values and the mean changes from baseline of each variable for participants in each treatment group. • Time to Event Variable: o Time to ALT normalisation in absence of rescue medication in participants with baseline ALT>ULN Population summary is the Turnbull’s estimator for non-parametric estimation of Time to ALT normalisation in each treatment arm • Intercurrent Events: Discontinuation of, interruption in, and non-adherence to GSK3228836 and PegIFN will be ignored (treatment policy); PegIFN ineligibility will be ignored (treatment policy); Rescue medication will be ignored (treatment policy), except for ALT normalisation which can only be achieved in the absence of rescue medication; Wide disruptive events (such as COVID-19 pandemic) leading to discontinuation of, interruption in, and nonadherence to GSK3228836 and PegIFN will be handled with Treatment Policy Strategy. • The group of estimands supporting this objective is the population summary for each variable in each treatment arm in the population regardless of discontinuation of, interruption in or non-adherence to GSK3228836 and | — |
Countries
Canada, China, Italy, Japan, Korea, Republic of, Poland, Russian Federation, South Africa, Spain, United Kingdom, United States
Contacts
Public ContactGSK Clinical Trials Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed