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Hepatitis BPhase 2B-FineNCT04544956

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

A Phase 2 study testing GSK3228836 and Nucleos(t)ide therapy in people with Hepatitis B, run by GlaxoSmithKline at 4 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatitis B
What is being tested?
GSK3228836 and Nucleos(t)ide therapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
4 sitesin 4 countries
Study dates
6 Oct 2020to 30 Nov 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • 1) 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:
  • 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.

Who cannot join

  • 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
Show all 42Show fewer
  • Both Aspartate aminotransferase (AST)-Platelet Index (APRI) >2 and FibroSure/FibroTest result >0.7
  • 1) 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 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.
  • 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.
  • 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.
  • Participants for whom immunosuppressive treatment is not advised, including therapeutic doses of steroids, will be excluded.
  • Currently taking, or took within 12 months of screening, any interferon-containing therapy.
  • Participants requiring anti-coagulation therapies (for example warfarin, Factor Xa inhibitors or anti-platelet agents like clopidogrel).
  • The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives (if known) or twice the duration (if known) of the biological effect of the study treatment (whichever is longer) or 90 days (if half-life or duration is unknown).
  • Prior treatment with any oligonucleotide or small interfering RNA (siRNA) within 12 months prior to the first dosing day.
  • Fridericia's QT correction formula (QTcF) >=450 milliseconds (msec) (if single electrocardiogram [ECG] at screening shows QTcF >=450 msec, a mean of triplicate measurements should be used to confirm that participant meets exclusion criterion).
  • Laboratory results as follows
  • Serum albumin <3.5 grams per deciliter (g/dL)
  • Glomerular filtration rate (GFR) <60 mL/minute/1.73 per meter square as calculated by the Chronic kidney disease- Epidemiologic Collaboration (CKD-EPI) formula.
  • International normalized Ratio (INR) >1.25
  • Platelet count <140 times 10^9/liter (L)
  • Total bilirubin >1.25 times ULN
  • For participants with benign unconjugated hyperbilirubinemia with total bilirubin >1.25 times ULN, discussion for inclusion to the study is required with the Medical Monitor
  • Urine albumin to creatinine ratio (ACR) >=0.03 mg/mg (or >=30 mg/g). In the event of an ACR above this threshold, eligibility may be confirmed by a second measurement 1) In cases where participants have low urine albumin and low urine creatinine levels resulting in a urine ACR calculation >=0.03 mg/mg (or >=30 mg/g), the investigator should confirm that the participant does not have a history of diabetes, hypertension or other risk factors that may affect renal function and discuss with the Medical Monitor, or designee.
  • History of/sensitivity to GSK3228836 or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.

Trial locations and contacts

4 sites in 4 countries.

4 sites in 4 countries

United States1 site

  • GSK Investigational Site

    Boston, Massachusetts, 02114

Other trials in United States

Canada1 site

  • GSK Investigational Site

    Toronto, Ontario, M5G 2C4

Other trials in Canada

Netherlands1 site

  • GSK Investigational Site

    Rotterdam, 3015 GD

Other trials in Netherlands

United Kingdom1 site

  • GSK Investigational Site

    London, E1 1BB

Other trials in United Kingdom

About this study

Official title: B-Fine: An Open Label, Single Arm Study to Mechanistically Interrogate the Therapeutic Effect of GSK3228836 in Patients With Chronic Hepatitis B Via Intrahepatic Immunophenotyping

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
Being tested
GSK3228836, Nucleos(t)ide therapy
Keywords
Hepatitis B virus, GSK3228836, Fine needle aspiration, Intrahepatic immunophenotyping
Medical subject headings
Hepatitis B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK3228836Drug

    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.

  • Nucleos(t)ide therapyDrug

    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.

Study groups in NCT04544956
Study groupRoleWhat they receive
GSK3228836 300 mgExperimentalParticipants 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).
Receives: Drug: GSK3228836; Drug: Nucleos(t)ide therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to Week 12

Secondary outcomes (15)

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

    Sustained HBsAg response is defined as HBsAg <LLOQ for 24 weeks from end of GSK3228836 treatment. Percentage values are rounded-off.

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

  2. 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

    Sustained virologic response is defined as HBsAg <LLOQ and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <LLOQ for 24 weeks from end of GSK3228836 treatment. Percentage values are rounded-off.

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

  3. Percentage of Participants Achieving HBsAg <LLOQ at Indicated Time Points

    Percentage of participants achieving HBsAg <LLOQ were assessed at indicated time points. Percentage values are rounded-off.

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

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

    Percentage of participants achieving HBV DNA <LLOQ were assessed at indicated time points. Percentage values are rounded-off.

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

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

    Percentage of participants achieving HBsAg <LLOQ and HBV DNA <LLOQ were assessed at indicated time points. Percentage values are rounded-off.

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

  6. Percentage of Participants With Categorical Change From Baseline in HBsAg Values at Indicated Time Points

    Participants who achieved a decline in HBsAg values from Baseline were reported. Participants were categorized in the following categorical HBsAg decline of <0.5, greater than or equal to (>=) 0.5, >=1, >=1.5, and >=3 log10 international units per milliliter (IU/mL). The 'HBsAg < LLOQ' category is derived based on Absolute/raw HBsAg result. The HBsAg decline categories are based on change from Baseline values. Percentage values are rounded-off.

    Measured: Baseline (Week -1), Treatment Week 12 and off treatment Week 24

  7. Number of Participants With Alanine Aminotransferase (ALT) Greater Than (>)3 Times Upper Limit of Normal (ULN) at Indicated Time Points

    Blood samples were collected at indicated time points to assess ALT levels. The ALT normalization (ALT <=upper limit of normal [ULN]) over time in absence of rescue medication in participants with Baseline ALT>ULN and ALT data at that visit. Participants who achieved ALT normalization were reported.

    Measured: Baseline (Week -1), treatment Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; off treatment Days 1, 8, 22, 50, 78, 106, 134 and 162

  8. Number of Participants With HBe Antibody (Anti-HBeAg) Levels

    Blood samples were collected to assess HBe antibody levels and results reported are for Baseline HBeAg positive participants.

    Measured: Baseline (Week -1), treatment Days 29, 36, and 57; off treatment Days 1, 8, 22, 50, 78, 106, 134 and 162

  9. Actual Values of HBsAg at Indicated Time Points

    Blood samples were collected from participants at indicated time points to assess HBsAg levels.

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

  10. Mean Change From Baseline in HBsAg at Indicated Time Points

    Blood samples were collected from participants at indicated time points to assess HBsAg levels. Change from Baseline was defined as value at the indicated time point minus Baseline value. Baseline was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

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

  11. Actual Values of HBV DNA at Indicated Time Points

    Blood samples were collected from participants at indicated time points to assess HBV DNA levels.

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

  12. Mean Change From Baseline in HBV DNA at Indicated Time Points

    Blood samples were collected from participants at indicated time points to assess HBV DNA levels. Change from Baseline was defined as value at the indicated time point minus Baseline value. Baseline was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

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

  13. Actual Values of HB Surface Antibody (Anti-HBsAg) Levels at Indicated Time Points

    Blood samples were collected from participants at indicated time points to assess anti-HBsAg levels.

    Measured: Baseline (Week -1) and off treatment Days 1 and 162

  14. Area Under the Concentration-time Curve (AUC) for ALT at Indicated Time Points

    Blood samples were collected from participants to assess AUC for ALT. On-treatment blood samples were collected from Weeks 1 to 12 and follow-up blood samples were collected from Weeks 12 to 36. AUC was calculated and presented for on-treatment (12 Weeks), follow-up (24 weeks), and On-treatment + follow-up (Weeks 1 to 36).

    Measured: Study Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 20, 24, 28, 32 and 36

  15. Time to Maximum ALT

    Time to maximum ALT (maximum peak in ALT) during 36 week (treatment + follow-up) is defined as time from Baseline to the time of first peak in ALT.

    Measured: Up to Study Week 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2020
  2. Study start6 Oct 2020
  3. Primary completion30 Nov 2023
  4. Study completion30 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
A single arm, multi-center, open label exploratory study.
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04544956
Sponsor's protocol ID
212602
Acronym
B-Fine
Status last verified
Apr 2025
First submitted
4 Sep 2020
Last updated
15 Jul 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK3228836 and Nucleos(t)ide therapy in people with Hepatitis B, run by GlaxoSmithKline at 4 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Canada, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Achieving Serum Hepatitis B Virus Surface Antigen (HBsAg) Level Less Than (<) Lower Limit of Quantitation (LLOQ) (time frame: Up to Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04544956.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2025.

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