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

NCT04544956 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 212602
• Study Type: interventional
• Target: 12
• Locations: 4 countries
• Sites: 4

Brief Summary

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.

Conditions

Hepatitis B

Keywords

Hepatitis B virus; GSK3228836; Fine needle aspiration; Intrahepatic immunophenotyping

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving Serum Hepatitis B Virus Surface Antigen (HBsAg) Level Less Than (<) Lower Limit of Quantitation (LLOQ)

  Percentage of participants achieving serum HBsAg level \<LLOQ were reported. Percentage values are rounded-off.

  Up to Week 12

Secondary Outcomes (15)

• Percentage of Participants With Sustained HBsAg Response (HBsAg <LLOQ) for 24 Weeks After the Planned and Actual End of GSK3228836 Treatment

  Up to 24 weeks off treatment (Study Weeks 12 to 36)

• Percentage of Participants Achieving Sustained Virologic Response (HBsAg <LLOQ and HBV DNA <LLOQ) for 24 Weeks After the Planned and Actual End of GSK3228836 Treatment

  Up to 24 weeks off treatment (Study Weeks 12 to 36)

• Percentage of Participants Achieving HBsAg <LLOQ at Indicated Time Points

  Baseline (Week -1), treatment Day 78 and off treatment (OT) Day 162

• Percentage of Participants Achieving HBV DNA <LLOQ at Indicated Time Points

  Baseline (Week -1), treatment Day 78 and off treatment Day 162

• Percentage of Participants Achieving HBsAg <LLOQ and HBV DNA <LLOQ at Indicated Time Points

  Baseline (Week -1), treatment Day 78 and off treatment Day 162

Study Arms (1)

GSK3228836 300 mg

EXPERIMENTAL

Participants on stable nucleos(t)ide therapy will receive GSK3228836 300 mg subcutaneously (SC) weekly once for 12 weeks along with a loading dose of GSK3228836 300 mg in Week 1 (Day 4) and Week 2 (Day 11).

Drug: GSK3228836; Drug: Nucleos(t)ide therapy

Interventions

GSK3228836 DRUG

GSK3228836 will be available as a clear colorless to slightly yellow solution for injection in 150 mg/milliliters (mL) vial to be administered SC once weekly.

GSK3228836 300 mg

Nucleos(t)ide therapy DRUG

Participants receiving nucleos(t)ide therapy upon entry in the study will continue to receive nucleos(t)ide therapy for the duration of the study.

GSK3228836 300 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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
• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

Boston, Massachusetts, 02114, United States

Location

GSK Investigational Site

Toronto, Ontario, M5G 2C4, Canada

Location

GSK Investigational Site

Rotterdam, 3015 GD, Netherlands

Location

GSK Investigational Site

London, E1 1BB, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A single arm, multi-center, open label exploratory study.

Study Record Dates

• First Submitted: September 4, 2020
• First Posted: September 10, 2020
• Study Start: October 6, 2020
• Primary Completion: November 30, 2023
• Study Completion: November 30, 2023
• Last Updated: July 15, 2025
• Results First Posted: December 19, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (1); NL (1); GB (1); CA (1)