Chronic Hepatitis B MedDRA version: 20.1 Level: PT Classification code 10008910 Term: Chronic 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: GSK3228836
Other descript
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 who have documented chronic HBV infection =6 months prior to screening AND currently receiving stable nucleos(t)ide analogue therapy, 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 3. Plasma or serum HBsAg concentration >100 IU/mL. 4. 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 2
Exclusion criteria
Exclusion criteria: 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 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 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 participants will be excluded from the study if their past history includes one of the following criteria: i. Liver biopsy showing Metavir 4 or equivalent 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 enrolment. 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. Positive (or borderline positive) ANCA at screening by itself won’t be an exclusion criterion - but if results are borderline positive or positive: Participants that meet this criteria may be considered for inclusion following: a. Analysis of MPO-ANCA [pANCA] and PR3-ANCA [cANCA] and b. A discussion with the Medical Monitor will be required to review participant’s complete medical history to ensure no past history or current manifestations of a vasculitic/inflammatory/auto-immune condition 9. Low C3 at screening or baseline AND evidence of past history or current manifestations of vasculitic/inflammatory/auto-immune condition a. All participants with low C3 at screening should have their medical history discussed with the Medical Monitor prior to enrolment. 10. 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 w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of 12 weeks of GSK3228836 on serum HBsAg levels in participants with CHB;Secondary Objective: Efficacy: To assess sustainability of serum HBsAg loss by GSK3228836 for up to 24 weeks off-treatment. To assess sustainability of serum HBsAg and HBV DNA loss by GSK3228836 for up to 24 weeks off treatment. To assess the effect of 12 weeks GSK3228836 on biomarkers and virus-specific antibody responses ;Primary end point(s): The Primary Estimand supporting the primary objective of the study is defined as: • Population: Participants with CHB who receive at least one dose of IP • Treatment: 300 mg GSK3228836 for 12 weeks (also on stable nucleos(t)ide therapy) • Variable: Achieving serum HBsAg level <LLOQ at any time point up to and including Week 12 without the use of PEG-interferon or other immunomodulator therapies • Population-level summary: Percent of participants that achieve serum HBsAg level <LLOQ • Intercurrent events: Discontinuation of, interruption of, and adherence to IP will be ignored (treatment policy). The primary estimand is the percentage of participants with CHB receiving 300 mg GSK3228836 for 12 weeks (with at least one dose of IP) who achieve serum HBsAg level <LLOQ at any time point up to and including Week 12, without the use of PEG-interferon or other immunomodulator therapies, regardless of completing IP, interruptions in IP or adherence to IP. ;Timepoint(s) of evaluation of this end point: 12 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The Estimand supporting the objective is defined as: • Population: Participants with CHB who receive at least one dose of IP • Treatment: 300 mg GSK3228836 for 12 weeks (also on stable nucleos(t)ide therapy) • Variables: o Sustained HBsAg Response (HBsAg 3X ULN at over time . HBe antibody (anti-HBeAg) levels over time Population summary: percentage of participants in each category. 2) Continuous Variables: • Actual values and change from baseline over time for HBsAg and HBV DNA • HBs antibody (anti-HBsAg) and HBe antibody (anti-HBeAg) levels over time • Area under the curve (AUC) for ALT on treatment (12 weeks), during follow up (24 weeks), and on treatment + follow up (36 weeks). Population summary: mean values and/or mean changes from baseline for each variable 3) Time to Event Variable • Time to Maximum ALT (ALT must be greater than 3xULN) during 36 weeks of treatment + follow up Population summary: Turnbull estimate for median Time to Maximum ALT (>3xULN) The group of estimands supporting this objective in participants with CHB receiving 300 mg GSK3228836 for 12 weeks (with at least one dose of IP) are the population summary for each variable in the absence of PEG-interferon or other immunomodulator therapies, regardless of completing IP, interruptions in IP, or adherence to IP. For remaining Endpoints please refer to the protocol P 27-28.;Timepoint(s) of evaluation of this end point: 12 Weeks | — |
Countries
Canada, Netherlands, United Kingdom, United States
Contacts
Public ContactClinical Trials Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed