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Hepatitis BPhase 2B-TogetherNCT04676724

Study of Sequential GSK3228836 and Peginterferon Treatment in Participants With Chronic Hepatitis B (CHB)

A Phase 2 study testing GSK3228836, PegIFN and NA therapy in people with Hepatitis B, run by GlaxoSmithKline at 49 sites in 11 countries.

Completed

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

Official record
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Trial summary

This study is intended to evaluate if 12 or 24 weeks of treatment with GSK3228836 followed by up to 24 weeks of pegylated interferon (PegIFN) can increase the rate of hepatitis B virus surface antigen (HBsAg) loss in participants on stable nucleos(t)ide analogue (NA) therapy, and whether virologic response can be… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Hepatitis B
What is being tested?
GSK3228836, PegIFN and NA therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
108 participants
Where
49 sitesin 11 countries
Study dates
28 Jan 2021to 17 Feb 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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 to 75 years of age at the time of signing the informed consent.
  • Participants who are eligible to be treated with PegIFN.
  • 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.
  • Plasma or serum HBsAg concentration >100 International Units per milliliter (IU/mL).
  • Plasma or serum HBV DNA concentration <90 IU/mL.
  • ALT <=2 times ULN.
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  • 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: a) Refrain from donating sperm; b) 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 agree to use contraception/barrier: 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 who is not currently pregnant.
  • A female participant is eligible to participate: a) If she is not pregnant or breastfeeding; b) at least one of the following conditions applies: Is not a woman of childbearing potential (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.
  • A WOCBP must have both a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
  • Capable of giving signed informed consent.

Who cannot join

  • Clinically significant abnormalities, aside from chronic HBV infection in medical history 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 of Fibrosure/FibroTest score, if the participant meets one of the following criteria, they will be excluded from the study: a) Liver biopsy (i.e., Metavir Score F4); b) Liver stiffness >12 kilopascals (kPa).
  • Diagnosed or suspected hepatocellular carcinoma as evidenced by the following: Alpha- fetoprotein concentration >=200 nanogram per milliliter (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 randomization.
  • 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).
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  • History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension).
  • Poorly controlled thyroid dysfunction or abnormal thyroid stimulating hormone (TSH) levels
  • Positive (or borderline positive) anti-neutrophil cytoplasmic antibody (ANCA) at screening. Participants that meet these criteria may be considered for inclusion in the study following: a) Analysis of myeloperoxidase (MPO)-ANCA [perinuclear ANCA (pANCA)] and PR3-ANCA [classical ANCA (cANCA)]; b) 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.
  • Low complement 3 (C3) at screening and evidence of past history or current manifestations of vasculitic/inflammatory/auto-immune conditions. All participants with low C3 at screening should have their medical history discussed with the Medical Monitor prior to enrolment.
  • 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.
  • Pre-existing severe psychiatric condition or a history of severe psychiatric disorders, including severe depression, suicidal ideation and attempted suicide.
  • 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.
  • Participants with prior treatment with PegINF or interferon will be excluded
  • Participants requiring anti-coagulation therapies (for example warfarin, Factor Xa inhibitors or anti-platelet agents like clopidogrel).
  • Participants currently taking, or took within 6 months of screening, telbivudine.
  • 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 ribonucleic acid (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 milliliter per minute per 1.73 square meter (mL/min /1.73 m^2) as calculated by the Chronic Kidney Disease Epidemiologic Collaboration (CKD-EPI) formula (for Japan, Japanese Society of Nephrology Chronic Kidney Disease Initiative [JSN-CKDI equation]); International normalized ratio (INR) >1.25; Platelet count <140x10^9 cells/L; Baseline hemoglobin <10 g/dL; 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 milligram (mg)/mg (or >=30 mg/g). In the event of an ACR above this threshold, eligibility may be confirmed by a second measurement. 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

49 sites in 11 countries.

49 sites in 11 countries

Japan7 sites

  • GSK Investigational Site

    Aichi, 467-8602

  • GSK Investigational Site

    Fukui, 918-8503

  • GSK Investigational Site

    Gifu, 500-8717

  • GSK Investigational Site

    Hiroshima, 737-0023

  • GSK Investigational Site

    Kumamoto, 860-8556

  • GSK Investigational Site

    Nagasaki, 856-8562

  • GSK Investigational Site

    Tokyo, 113-8603

Other trials in Japan

Russia7 sites

  • GSK Investigational Site

    Barnaul, 656010

  • GSK Investigational Site

    Chelyabinsk, 454052

  • GSK Investigational Site

    Moscow, 121170

  • GSK Investigational Site

    Novosibirsk, 630099

  • GSK Investigational Site

    Saint Petersburg, 190103

  • GSK Investigational Site

    Samara, 443063

  • GSK Investigational Site

    Красноярск, 660049

Other trials in Russia

China5 sites

  • GSK Investigational Site

    Beijing, 100015

  • GSK Investigational Site

    Beijing, 100069

  • GSK Investigational Site

    Changchun, Jilin, 130021

  • GSK Investigational Site

    Hangzhou, 310000

  • GSK Investigational Site

    Shanghai, 200025

Other trials in China

South Korea5 sites

  • GSK Investigational Site

    Busan, 49241

  • GSK Investigational Site

    Daegu, 41944

  • GSK Investigational Site

    Gyeonggi-do, 15355

  • GSK Investigational Site

    Gyeonggi-do, 463-712

  • GSK Investigational Site

    Ulsan, 44033

Other trials in South Korea

Spain5 sites

  • GSK Investigational Site

    Barcelona, 08011

  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    Madrid, 28031

  • GSK Investigational Site

    Málaga, 29010

  • GSK Investigational Site

    Santander, 39008

Other trials in Spain

United States4 sites

  • GSK Investigational Site

    Detroit, Michigan, 48202

  • GSK Investigational Site

    Iowa City, Iowa, 52242

  • GSK Investigational Site

    New York, New York, 10016

  • GSK Investigational Site

    Sacramento, California, 95817

Other trials in United States

Italy4 sites

  • GSK Investigational Site

    Baggiovara (MO), Emilia-Romagna, 40126

  • GSK Investigational Site

    Milan, Lombardy, 20122

  • GSK Investigational Site

    Milan, Lombardy, 20157

  • GSK Investigational Site

    Monza (MB), Lombardy, 20900

Other trials in Italy

United Kingdom4 sites

  • GSK Investigational Site

    London, WC1E 6JB

  • GSK Investigational Site

    Newcastle upon Tyne, NE7 7DN

  • GSK Investigational Site

    Nottingham, NG7 2UH

  • GSK Investigational Site

    Plymouth, PL68DH

Other trials in United Kingdom

Canada3 sites

  • GSK Investigational Site

    Calgary, Alberta, T2N 4Z6

  • GSK Investigational Site

    Edmonton, Alberta, T6G 2X8

  • GSK Investigational Site

    Montreal, Quebec, H2L 4E9

Other trials in Canada

Poland3 sites

  • GSK Investigational Site

    Łańcut, 37-100

  • GSK Investigational Site

    Lublin, 20-884

  • GSK Investigational Site

    Mysłowice, 41-400

Other trials in Poland

South Africa2 sites

  • GSK Investigational Site

    Ennerdale, Gauteng, 1830

  • GSK Investigational Site

    Johannesburg, Gauteng, 1401

Other trials in South Africa

About this study

Official title: A Phase IIb Multi-Center, Randomised, Open Label Study to Assess the Efficacy and Safety of Sequential Treatment With GSK3228836 Followed by Pegylated Interferon Alpha 2a in Participants With Chronic Hepatitis B Virus (B-Together)

This study is intended to evaluate if 12 or 24 weeks of treatment with GSK3228836 followed by up to 24 weeks of pegylated interferon (PegIFN) can increase the rate of hepatitis B virus surface antigen (HBsAg) loss in participants on stable nucleos(t)ide analogue (NA) therapy, and whether virologic response can be sustained once PegIFN treatment is discontinued. Participants will be randomized to receive GSK3228836 for 12 or 24 weeks followed by up to 24 weeks of PegIFN.

Conditions
Hepatitis B
Being tested
GSK3228836, PegIFN, NA therapy
Keywords
Chronic Hepatitis B, GSK3228836, Pegylated interferon, Nucleos(t)ide analogue, Sustained virologic response
Medical subject headings
Hepatitis B, Hepatitis B, Chronic

What participants receive

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

  • GSK3228836Drug

    Participants will be administered GSK3228836.

  • PegIFNDrug

    Participants will be administered PegIFN.

  • NA therapyDrug

    Participants will continue to receive their NA therapy for the duration of the study.

Study groups in NCT04676724
Study groupRoleWhat they receive
GSK3228836 300 mg (24 weeks) + PegIFN 180 mcg (24 weeks)ExperimentalParticipants on stable NA therapy received 300 milligrams per week (mg/week) GSK3228836 for 24 weeks (plus a loading dose on Day 4 and 11), followed by Pegylated Interferon (PegIFN) 180 microgram per week (mcg/week) up to 24 weeks.
Receives: Drug: GSK3228836; Drug: PegIFN; Drug: NA therapy
GSK3228836 300 mg (12 weeks) + PegIFN 180 mcg (24 weeks)ExperimentalParticipants on stable NA therapy received 300mg/week GSK3228836 for 12 weeks (plus a loading dose on Day 4 and 11), followed by PegIFN 180 mcg/week up to 24 weeks.
Receives: Drug: GSK3228836; Drug: PegIFN; Drug: NA therapy

What is being measured

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

  1. Treatment Arm 1 - Percentage of Participants Achieving Sustained Virologic Response (SVR) for 24 Weeks After End of Treatment

    Sustained virologic response is defined as undetectable levels of Hepatitis B surface antigen (HBsAg) and Hepatitis-B virus deoxy-ribonucleic acid (HBV DNA) on treatment. The SVR was a composite endpoint defined as HBsAg and HBV DNA levels were less than (<) Lower limit of quantitation (LLOQ) at the planned end of sequential treatment of GSK3228836 and PegIFN treatment which is sustained for 24 weeks post-GSK3228836 and PegIFN treatment in the absence of any rescue medication. Percentage values are rounded-off.

    Measured: Up to 24 weeks off treatment (Study Weeks 48 to 72)

  2. Treatment Arm 2 - Percentage of Participants Achieving Sustained Virologic Response (SVR) for 24 Weeks After End of Treatment

    Sustained virologic response is defined as undetectable levels of Hepatitis B surface antigen (HBsAg) and Hepatitis-B virus deoxy-ribonucleic acid (HBV DNA) on treatment. The SVR was a composite endpoint defined as HBsAg and HBV DNA levels were less than (<) Lower limit of quantitation (LLOQ) at the planned end of sequential treatment of GSK3228836 and PegIFN treatment which is sustained for 24 weeks post-GSK3228836 and PegIFN treatment in the absence of any rescue medication. Percentage values are rounded-off.

    Measured: Up to 24 weeks off treatment (Study Weeks 36 to 60)

Secondary outcomes (33)

  1. Treatment Arm 1: Percentage of Participants Achieving HBsAg and HBV DNA < Lower Limit of Quantitation (LLOQ)

    Percentage of participants achieving HBsAg and HBV DNA <LLOQ were reported. Percentage values are rounded-off.

    Measured: End of treatment (up to 48 weeks) and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  2. Treatment Arm 2: Percentage of Participants Achieving HBsAg and HBV DNA < Lower Limit of Quantitation (LLOQ)

    Percentage of participants achieving HBsAg and HBV DNA <LLOQ were reported. Percentage values are rounded-off.

    Measured: End of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60) and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  3. Treatment Arm 1: Percentage of Participants With Categorical Changes From Baseline in HBsAg Values

    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, End of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  4. Treatment Arm 2: Percentage of Participants With Categorical Changes From Baseline in HBsAg Values

    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, End of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60) and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  5. Treatment Arm 1: Number of Participants With Alanine Aminotransferase (ALT) Normalization

    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: At baseline, end of treatment (up to 48 weeks) and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  6. Treatment Arm 2: Number of Participants With Alanine Aminotransferase (ALT) Normalization

    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: At baseline, End of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  7. Treatment Arm 1: 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: At baseline, end of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  8. Treatment Arm 2: 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: At baseline, End of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  9. Treatment Arm 1: Mean Change From Baseline in HBe Antibody Levels

    Blood samples were collected to assess HBe antibody levels and results reported are for baseline HBeAg positive participants. 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: At baseline, end of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  10. Treatment Arm 2: Mean Change From Baseline in HBe Antibody Levels

    Blood samples were collected to assess HBe antibody levels and results reported are for baseline HBeAg positive participants. 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: At baseline, End of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  11. Treatment Arm 1: Actual Values of HBsAg Levels

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

    Measured: At baseline, end of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  12. Treatment Arm 2: Actual Values of HBsAg Levels

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

    Measured: At baseline, end of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  13. Treatment Arm 1: Mean Change From Baseline in HBsAg Levels

    Blood samples were collected to assess HBsAg change from baselines 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: At baseline, end of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  14. Treatment Arm 2: Mean Change From Baseline in HBsAg Levels

    Blood samples were collected to assess HBsAg change from baselines 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: At baseline, end of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  15. Treatment Arm 1: Actual Values of HBV DNA Levels

    Blood samples were collected to assess HBV DNA levels.

    Measured: At baseline, end of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  16. Treatment Arm 2: Actual Values of HBV DNA Levels

    Blood samples were collected to assess HBV DNA levels.

    Measured: At baseline, end of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  17. Treatment Arm 1: Mean Change From Baseline in HBV DNA Levels

    Blood samples were collected 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: At baseline, end of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  18. Treatment Arm 2: Mean Change From Baseline in HBV DNA Levels

    Blood samples were collected 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: At baseline, end of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  19. Treatment Arm 1: Actual Values of Hepatitis B Virus E-antigen (HBeAg) Levels

    Blood samples were collected to assess HBeAg levels.

    Measured: At baseline, end of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  20. Treatment Arm 2: Actual Values of Hepatitis B Virus E-antigen (HBeAg) Levels

    Blood samples were collected to assess HBeAg levels.

    Measured: At baseline, end of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  21. Treatment Arm 1: Mean Change From Baseline in HBeAg Levels

    Blood samples were collected to assess HBeAg 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: At baseline, end of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  22. Treatment Arm 2: Mean Change From Baseline in HBeAg Levels

    Blood samples were collected to assess HBeAg 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: At baseline, end of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  23. Treatment Arm 1: Actual Values of HBs Antibody Levels

    Blood samples were collected to assess HBs antibody levels.

    Measured: At baseline, end of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  24. Treatment Arm 2: Actual Values of HBs Antibody Levels

    Blood samples were collected to assess HBs antibody levels.

    Measured: At baseline, end of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  25. Treatment Arm 1: Mean Change From Baseline in HBs Antibody Levels

    Blood samples were collected to assess HBs antibody levels over time. 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: At baseline, end of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  26. Treatment Arm 2: Mean Change From Baseline in HBs Antibody Levels

    Blood samples were collected to assess HBs antibody levels over time. 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: At baseline, end of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  27. Treatment Arm 1: Actual Values of ALT

    Blood samples were collected to assess ALT mean values.

    Measured: At baseline, end of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  28. Treatment Arm 2: Actual Values of ALT

    Blood samples were collected to assess ALT mean values.

    Measured: At baseline, end of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  29. Treatment Arm 1: Change From Baseline in ALT

    Blood samples were collected to assess ALT values. 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: At baseline, end of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

  30. Treatment Arm 2: Change From Baseline in ALT

    Blood samples were collected to assess ALT values. 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: At baseline, end of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60), and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

  31. Treatment Arm 1 - Median Time to ALT Normalization in Absence of Rescue Medication for 24 Weeks After End of Treatment

    Time to ALT normalization in absence of rescue medication were measured in participants having Baseline ALT>ULN.

    Measured: Up to 24 weeks off treatment (Study Week 48 to72)

  32. Treatment Arm 2 - Median Time to ALT Normalization in Absence of Rescue Medication for 24 Weeks After End of Treatment

    Time to ALT normalization in absence of rescue medication were measured in participants having Baseline ALT>ULN.

    Measured: Up to 24 weeks off treatment (Study Weeks 36 to 60)

  33. Percentage of Participants Achieving Sustained Virologic Response (SVR) for 24 Weeks Off Treatment for Comparison of Efficacy Between Different Treatment Durations

    Sustained virologic response is defined as undetectable levels of HBsAg and Hepatitis-B virus deoxy-ribonucleic acid (HBV DNA) on treatment. The SVR was a composite endpoint defined as Hepatitis B surface antigen (HBsAg) and Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) levels were less than (<) Lower limit of quantitation (LLOQ) at the planned end of GSK3228836 treatment which is sustained for 24 weeks post-GSK3228836 treatment in the absence of rescue medication. The point estimate for the difference in SVR and its respective credible interval (CI) were evaluated at 24 weeks off of planned treatment for both arms. The comparison of efficacy is between treatment durations and timepoint corresponds to Week 72 in Arm 1 and Week 60 in Arm 2. 95% CI here refers as credible interval. Percentage values are rounded-off.

    Measured: Up to 24 weeks off treatment (Treatment Arm 1: Study Weeks 48 to 72 and Treatment Arm 2: Study Weeks 36 to 60)

Timeline

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

  1. First posted21 Dec 2020
  2. Study start28 Jan 2021
  3. Primary completion17 Feb 2023
  4. Study completion17 Feb 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
Randomised
Intervention model
Parallel groups
Model description
Participants will be randomised in a ratio of 1:1 to one of two treatment arms: 24 weeks GSK3228836 followed by up to 24 weeks PegIFN, or 12 weeks GSK3228836 followed by up to 24 weeks PegIFN.
Masking
None (open label)
Enrolment
108 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04676724
Sponsor's protocol ID
209348
Acronym
B-Together
Status last verified
Apr 2024
First submitted
15 Dec 2020
Last updated
2 May 2024
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.

Publications

  • Joshi S, Freudenberg JM, Singh JM, Jordan WT, Felton L, Dixon S, Paff M, Theodore D, Walker J. Immunomodulation by bepirovirsen may induce killing of infected hepatocytes (B-Together study). Hepatol Int. 2026 Feb;20(1):46-58. doi: 10.1007/s12072-025-10917-0. Epub 2025 Oct 3.

    PubMed 41042426

  • Buti M, Heo J, Tanaka Y, Andreone P, Atsukawa M, Cabezas J, Chak E, Coffin CS, Fujiwara K, Gankina N, Gordon SC, Janczewska E, Komori A, Lampertico P, McPherson S, Morozov V, Plesniak R, Poulin S, Ryan P, Sagalova O, Sheng G, Voloshina N, Xie Q, Yim HJ, Dixon S, Paff M, Felton L, Lee M, Greene T, Lim J, Lakshminarayanan D, McGonagle G, Plein H, Youssef AS, Elston R, Kendrick S, Theodore D. Sequential Peg-IFN after bepirovirsen may reduce post-treatment relapse in chronic hepatitis B. J Hepatol. 2025 Feb;82(2):222-234. doi: 10.1016/j.jhep.2024.08.010. Epub 2024 Aug 29.

    PubMed 39214467

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK3228836, PegIFN and NA therapy in people with Hepatitis B, run by GlaxoSmithKline at 49 sites in 11 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 10 inclusion and 22 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 2 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in Japan, Russia, China, South Korea, Spain and 6 more countries. 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 2 May 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?

Treatment Arm 1 - Percentage of Participants Achieving Sustained Virologic Response (SVR) for 24 Weeks After End of Treatment (time frame: Up to 24 weeks off treatment (Study Weeks 48 to 72)). The study lists 2 primary outcomes in all. 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 NCT04676724, which also lists 2 linked publications.

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 2 May 2024.

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