A Mechanistic Study of GSK3228836 With Fine Needle Aspiration (FNA) in Participants With Chronic Hepatitis B

Completed · Phase 2

Conditions studied: Hepatitis B

In brief

Hepatitis B virus (HBV) infection, especially chronic, is a significant worldwide medical problem. This is an exploratory study of the therapeutic mechanism of GSK3228836 in participants with chronic hepatitis B (CHB) on stable nucleos(t)ide therapy (which is the first line therapy for CHB). This study is a Phase IIa, multi-center open label exploratory study of the therapeutic mechanism of GSK3228836 in participants with hepatitis B virus e-antigen (HBeAg)-negative CHB on stable nucleos(t)ide therapy using repeat fine needle aspirations of the liver for intrahepatic immunophenotyping. It will investigate the virologic and immunologic correlates of hepatitis B virus surface antigen (HBsAg) loss observed in participants when treated for 12 weeks with 300 milligrams (mg) GSK3228836. Repeat fine needle aspirates of the liver will be performed to enable analysis of liver-resident immune cells to investigate any immunomodulatory properties of GSK3228836 and to study the biology of underlying treatment-associated liver flares. The study will consist of a screening, treatment, and post-treatment follow-up phase. Approximately 20 participants will be enrolled in the study.

Key facts

Study ID

NCT04544956

Run by

GlaxoSmithKline

People needed

12

Starts

2020-10-06

Expected to finish

2023-11-30

Last updated by the study team

2025-07-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants should be at least 18 years of age at the time of signing the informed consent.
• 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.
• Plasma or serum HBsAg concentration >100 IU/mL
• Plasma or serum HBV DNA concentration must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL.
• HBeAg-negative
• ALT less than or equal to (<=)2 times ULN
• No gender restriction.
• A male participant is eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of study treatment i. Refrain from donating sperm ii. and be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or Must agree to use contraception/barrier as detailed below
• Agree to use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak) when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.
• A female participant is eligible to participate:
• i. If she is not pregnant or breastfeeding. ii. and at least one of the following conditions applies:
• Is not a WOCBP
• or is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1 percent [%] per year), preferably with low user dependency during the intervention period and for at least 90 days after the last dose of study treatment iii. A WOCBP must have both
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• A confirmed menstrual period prior to the first dose of study intervention (additional evaluation [e.g. amenorrhea in athletes, birth control] should also be considered)
• and a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study treatment
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

You may not qualify if…

• 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.
• Co-infection with:
• Current or past history of Hepatitis C virus (HCV)
• Human immunodeficiency virus (HIV)
• Hepatitis D virus (HDV).
• History of or suspected liver cirrhosis and/or evidence of cirrhosis as determined by
• Both Aspartate aminotransferase (AST)-Platelet Index (APRI) >2 and FibroSure/FibroTest result >0.7
• 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.
• Regardless of APRI or Fibrosure/FibroTest score participants will be excluded from the study if their past history includes one of the following criteria:
• Liver biopsy showing Metavir 4 or equivalent
• Liver stiffness >12 kilopascals (kPa)
• Diagnosed or suspected hepatocellular carcinoma as evidenced by the following
• Alpha-fetoprotein concentration >=200 nanograms (ng)/mL
• 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.
• 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.
• 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).
• History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension).
• Anti-neutrophil cytoplasmic antibody (ANCA) at screening by itself won't be an exclusion criterion - but if results are borderline positive or positive:
• Myeloperoxidase (MPO)-ANCA (perinuclear [p] ANCA) and Proteinase 3 (PR3)-ANCA (Cytoplasmic [c] ANCA) analysis will be conducted
• 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 before inclusion in study is permitted.
• Low compliment (C)3 at screening or Baseline by itself won't be an exclusion criterion-but if it is present
• a. A discussion with the Medical Monitor is required to review participant's complete medical history to ensure no past history or current manifestations of vasculitic/inflammatory/auto-immune conditions.
• History of alcohol or drug abuse/dependence
• Current alcohol use as judged by investigator to potentially interfere with participant compliance.
• History of or current drug abuse/dependence as judged by the investigator to potentially interfere with participant compliance.

Where it is running

• GSK Investigational Site — Boston, Massachusetts, United States
• GSK Investigational Site — Toronto, Ontario, Canada
• GSK Investigational Site — Rotterdam, Netherlands
• GSK Investigational Site — London, United Kingdom

Full record on ClinicalTrials.gov

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