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AzTrials

Hepatitis BPhase 2B-ClearNCT04449029

A Study of GSK3228836 in Participants With Chronic Hepatitis B (CHB)

A Phase 2 study testing GSK3228836 and Nucleos(t)ide therapy in people with Hepatitis B, run by GlaxoSmithKline at 121 sites in 22 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

Chronic hepatitis B virus (HBV) infection is a significant worldwide medical problem. GSK3228836 demonstrated target engagement in CHB participants who were not on treatment and in CHB participants on stable nucleos(t)ide therapy. 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?
Yes, some participants may receive a placebo
How many people
457 participants
Where
121 sitesin 22 countries
Study dates
27 Jul 2020to 18 Mar 2022
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

  • At least 18 years of age at the time of signing the informed consent.
  • Participants who have documented chronic HBV infection greater than equal to (>=6) months prior to screening and not currently on nucleos(t)ide analogue therapy population defined as participants who never received HBV treatment (treatment naive) or must have ended nucleos(t)ide therapy at least 6 months prior to the screening visit; OR Currently receiving stable nucleos(t)ide analogue therapy population 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 international units per milliliter (IU/mL).
  • Plasma or serum HBV DNA concentration: Participants not currently on nucleos(t)ide analogue therapy, plasma or serum HBV DNA >2000 IU/mL; Participants who are receiving stable nucleos(t)ide analogue therapy must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL.
  • ALT for treatment naive participants and for participants who are not currently receiving treatment: ALT <3 times ULN will be included initially if agreed by the independent data monitoring committee (IDMC) after review of safety data, the ALT inclusion criteria may be expanded to include participants with ALT <5 times ULN; ALT less than equal to (<=2) times ULN for participants who are receiving stable nucleos(t)ide analogue therapy.
  • Male and/or Female: 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: Refrain from donating sperm 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 who is not currently pregnant. A female participant is eligible to participate: If she is not pregnant or breastfeeding AND 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 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.
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  • Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • Capable of giving signed informed consent.

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 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: Liver biopsy (i.e., Metavir Score F4); 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).
  • Anti-neutrophil cytoplasmic antibodies (ANCA) at screening by itself won't be an exclusion criterion, but if results are borderline positive or positive: myeloperoxidase-ANCA (MPO-ANCA) (Perinuclear antineutrophil cytoplasmic antibodies [pANCA]) and proteinase 3- ANCA (PR3-ANCA) (Cytoplasmic antineutrophil cytoplasmic antibodies [cANCA]) 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 complement C3 (C3) at screening 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 ribonucleic acid (RNA) (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 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 <140 times 10^9 cells/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. 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

121 sites in 22 countries.

121 sites in 22 countries

Japan14 sites

  • GSK Investigational Site

    Ehime, 790-8524

  • GSK Investigational Site

    Hiroshima, 730-8619

  • GSK Investigational Site

    Hiroshima, 734-8551

  • GSK Investigational Site

    Hokkaido, 080-0024

  • GSK Investigational Site

    Ishikawa, 920-8650

  • GSK Investigational Site

    Ishikawa, 924-8588

  • GSK Investigational Site

    Kagawa, 760-8557

  • GSK Investigational Site

    Kumamoto, 860-8556

  • GSK Investigational Site

    Kumamoto, 862-8655

  • GSK Investigational Site

    Miyagi, 980-8574

  • GSK Investigational Site

    Nagasaki, 856-8562

  • GSK Investigational Site

    Osaka, 565-0871

  • GSK Investigational Site

    Tokyo, 113-8603

  • GSK Investigational Site

    Tokyo, 180-8610

Other trials in Japan

Russia11 sites

  • GSK Investigational Site

    Chelyabinsk, 454052

  • GSK Investigational Site

    Kaliningrad, 236016

  • GSK Investigational Site

    Krasnodar, 350000

  • GSK Investigational Site

    Moscow, 121170

  • GSK Investigational Site

    Moscow, 125008

  • GSK Investigational Site

    Novosibirsk, 630005

  • GSK Investigational Site

    Novosibirsk, 630099

  • GSK Investigational Site

    Saint Petersburg, 190103

  • GSK Investigational Site

    Saint Petersburg, 191167

  • GSK Investigational Site

    Samara, 443063

  • GSK Investigational Site

    Красноярск, 660049

Other trials in Russia

South Korea9 sites

  • GSK Investigational Site

    Busan, 47392

  • GSK Investigational Site

    Busan, 49241

  • GSK Investigational Site

    Daegu, 41944

  • GSK Investigational Site

    Gyeonggi-do, 15355

  • GSK Investigational Site

    Incheon, 21565

  • GSK Investigational Site

    Seoul, 03080

  • GSK Investigational Site

    Seoul, 05505

  • GSK Investigational Site

    Seoul, 06973

  • GSK Investigational Site

    Ulsan, 44033

Other trials in South Korea

United States8 sites

  • GSK Investigational Site

    Boston, Massachusetts, 02114

  • GSK Investigational Site

    Decatur, Georgia, 30033

  • GSK Investigational Site

    Los Angeles, California, 90089

  • GSK Investigational Site

    Miami, Florida, 33125

  • GSK Investigational Site

    Miami, Florida, 33136

  • GSK Investigational Site

    New York, New York, 10016

  • GSK Investigational Site

    Pittsburgh, Pennsylvania, 15213

  • GSK Investigational Site

    Richmond, Virginia, 23249

Other trials in United States

China8 sites

  • GSK Investigational Site

    Beijing, 100015

  • GSK Investigational Site

    Beijing, 100034

  • GSK Investigational Site

    Beijing, 100050

  • GSK Investigational Site

    Chongqing, Sichuan, 400042

  • GSK Investigational Site

    Guangzhou, 510000

  • GSK Investigational Site

    Shanghai, 200025

  • GSK Investigational Site

    Shenyang, Liaoning, 110022

  • GSK Investigational Site

    Wuhan, Hubei, 430030

Other trials in China

Romania8 sites

  • GSK Investigational Site

    Brasov, 500283

  • GSK Investigational Site

    Bucharest, 030303

  • GSK Investigational Site

    Cluj-Napoca, 400139

  • GSK Investigational Site

    Cluj-Napoca, 400162

  • GSK Investigational Site

    Craiova, 200515

  • GSK Investigational Site

    Galati, 800179

  • GSK Investigational Site

    Iași, 700116

  • GSK Investigational Site

    Timișoara, 300310

Other trials in Romania

Spain8 sites

  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    Barcelona, 08036

  • GSK Investigational Site

    Madrid, 28029

  • GSK Investigational Site

    Madrid, 28031

  • GSK Investigational Site

    Majadahonda (Madrid), 28222

  • GSK Investigational Site

    Málaga, 29010

  • GSK Investigational Site

    Santander, 39008

  • GSK Investigational Site

    Seville, 41013

Other trials in Spain

Canada7 sites

  • GSK Investigational Site

    Calgary, Alberta, T2N 4Z6

  • GSK Investigational Site

    London, Ontario, N6A 2C2

  • GSK Investigational Site

    Montreal, Quebec, H2L 4E9

  • GSK Investigational Site

    Québec, G1V 4G2

  • GSK Investigational Site

    Regina, Saskatchewan, S4P 0W5

  • GSK Investigational Site

    Toronto, Ontario, M5G 2C4

  • GSK Investigational Site

    Victoria, British Columbia, V8V 3M9

Other trials in Canada

France6 sites

  • GSK Investigational Site

    Clichy, 92118

  • GSK Investigational Site

    Créteil, 94010

  • GSK Investigational Site

    Limoges, 87042

  • GSK Investigational Site

    Lyon, 69317

  • GSK Investigational Site

    Nice, 06202

  • GSK Investigational Site

    Strasbourg, 67200

Other trials in France

South Africa6 sites

  • GSK Investigational Site

    Durban, KwaZulu-Natal, 4052

  • GSK Investigational Site

    Ennerdale, Gauteng, 1830

  • GSK Investigational Site

    Kwaguqa Emalahleni, Mpumalanga, 1039

  • GSK Investigational Site

    Lenasia Johannesburg, Gauteng, 1827

  • GSK Investigational Site

    Port Elizabeth, Eastern Cape, 6001

  • GSK Investigational Site

    Vosloorus Ext 2, 1475

Other trials in South Africa

Germany5 sites

  • GSK Investigational Site

    Berlin, 10439

  • GSK Investigational Site

    Erlangen, Bavaria, 91054

  • GSK Investigational Site

    Frankfurt am Main, Hesse, 60590

  • GSK Investigational Site

    Frankfurt am Main, Hesse, 60596

  • GSK Investigational Site

    Hamburg, 20146

Other trials in Germany

Thailand5 sites

  • GSK Investigational Site

    Bangkok, 10330

  • GSK Investigational Site

    Bangkok, 10400

  • GSK Investigational Site

    Chiang Mai, 50200

  • GSK Investigational Site

    Phitsanulok, 65000

  • GSK Investigational Site

    Songkhla, 9110

Other trials in Thailand

Bulgaria4 sites

  • GSK Investigational Site

    Sliven, 8800

  • GSK Investigational Site

    Sofia, 1431

  • GSK Investigational Site

    Sofia, 1463

  • GSK Investigational Site

    Sofia, 1527

Other trials in Bulgaria

Italy4 sites

  • GSK Investigational Site

    Milan, Lombardy, 20122

  • GSK Investigational Site

    Milan, Lombardy, 20132

  • GSK Investigational Site

    Milan, Lombardy, 20157

  • GSK Investigational Site

    Modena, Emilia-Romagna, 41126

Other trials in Italy

Poland4 sites

  • GSK Investigational Site

    Łańcut, 37-100

  • GSK Investigational Site

    Lublin, 20-884

  • GSK Investigational Site

    Mysłowice, 41-400

  • GSK Investigational Site

    Warsaw, 00-332

Other trials in Poland

Singapore3 sites

  • GSK Investigational Site

    Singapore, 119074

  • GSK Investigational Site

    Singapore, 169608

  • GSK Investigational Site

    Singapore, 529889

Other trials in Singapore

United Kingdom3 sites

  • GSK Investigational Site

    London, WC1E 6JB

  • GSK Investigational Site

    Newcastle upon Tyne, NE7 7DN

  • GSK Investigational Site

    Plymouth, PL6 8DH

Other trials in United Kingdom

Argentina2 sites

  • GSK Investigational Site

    Buenos Aires, C1280AEB

  • GSK Investigational Site

    Ciudad Autonoma de Buenos Aires, Buenos Aires, C1181ACH

Other trials in Argentina

Philippines2 sites

  • GSK Investigational Site

    Makati City, 1229

  • GSK Investigational Site

    Quezon City, 1101

Other trials in Philippines

Taiwan2 sites

  • GSK Investigational Site

    Changhua, 500

  • GSK Investigational Site

    Taichung, 40447

Other trials in Taiwan

Hong Kong1 site

  • GSK Investigational Site

    Pokfulam

Other trials in Hong Kong

Malaysia1 site

  • GSK Investigational Site

    Kuala Lumpur, 59100

Other trials in Malaysia

About this study

Official title: Phase IIb Multi-Center, Randomised, Partial-Blind Parallel Cohort Study to Assess the Efficacy and Safety of Treatment With GSK3228836 in Participants With Chronic Hepatitis B Virus (B-Clear)

Chronic hepatitis B virus (HBV) infection is a significant worldwide medical problem. GSK3228836 demonstrated target engagement in CHB participants who were not on treatment and in CHB participants on stable nucleos(t)ide therapy. This study is intended to evaluate if treatment with GSK3228836 can achieve sustained virologic response (SVR), that is hepatitis B virus surface antigen (HBsAg) less than (<) lower limit of quantitation (LLOQ) and HBV deoxyribonucleic acid (DNA) <LLOQ sustained for 24 weeks post-GSK3228836 treatment end. In addition, the study will also evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic properties of GSK3228836 in the 4 dosing regimens. This study will assess the efficacy and safety of treatment with GSK3228836 in two populations of participants with CHB; participants on stable nucleos(t)ide treatment (Cohort 1) and participants who are not currently on nucleos(t)ide therapy (Cohort 2). For each population, participants will be randomized into one of the 4 different parallel arms to receive treatment. The study will consist of a screening, treatment, and post-treatment follow-up phase. Approximately, 440 participants will be enrolled in the study.

Conditions
Hepatitis B
Being tested
GSK3228836, Placebo, Nucleos(t)ide therapy
Keywords
Chronic Hepatitis B, GSK3228836, Hepatitis B virus surface antigen, Nucleos(t)ide therapy, 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

    GSK3228836 will be available as a clear colorless to slightly yellow solution for injection at a unit dose strength of 150 mg/mL to be administered subcutaneously once weekly.

  • PlaceboDrug

    Placebo will be available as a clear colorless solution for injection to be administered subcutaneously once weekly.

  • Nucleos(t)ide therapyDrug

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

Study groups in NCT04449029
Study groupRoleWhat they receive
Cohort 1: GSK3228836 300 mg + LDExperimentalEligible participants on stable nucleos(t)ide treatment will receive 300 milligrams (mg) GSK3228836 once weekly for 24 weeks along with loading dose (LD) of 300 mg GSK3228836 on Day 4 and Day 11.
Receives: Drug: GSK3228836; Drug: Nucleos(t)ide therapy
Cohort 1: GSK3228836 300 mg + LD/ GSK3228836 150 mg + PlaceboExperimentalEligible participants on stable nucleos(t)ide treatment will receive 300 mg GSK3228836 once weekly for 12 weeks along with LD of 300 mg GSK3228836 on Day 4 and Day 11 followed by step-down in dose of 150 mg GSK3228836 once weekly for 12 weeks along with placebo to match to maintain participant blinding.
Receives: Drug: GSK3228836; Drug: Placebo; Drug: Nucleos(t)ide therapy
Cohort 1: GSK3228836 300 mg + LD/ PlaceboExperimentalEligible participants on stable nucleos(t)ide treatment will receive 300 mg GSK3228836 once weekly for 12 weeks along with LD of 300 mg GSK3228836 on Day 4 and Day 11 followed by placebo once weekly for 12 weeks.
Receives: Drug: GSK3228836; Drug: Placebo; Drug: Nucleos(t)ide therapy
Cohort 1: Placebo/ GSK3228836 300 mg + Placebo LDExperimentalEligible participants on stable nucleos(t)ide treatment will receive placebo once weekly for 12 weeks followed by 300 mg GSK3228836 once weekly for 12 weeks along with placebo LD to match on Day 4 and Day 11.
Receives: Drug: GSK3228836; Drug: Placebo; Drug: Nucleos(t)ide therapy
Cohort 2: GSK3228836 300 mg + LDExperimentalEligible participants not currently on nucleos(t)ide therapy will receive 300 mg GSK3228836 once weekly for 24 weeks along with LD of 300 mg GSK3228836 on Day 4 and Day 11.
Receives: Drug: GSK3228836
Cohort 2: GSK3228836 300 mg + LD/ GSK3228836 150 mg + PlaceboExperimentalEligible participants not currently on nucleos(t)ide therapy will receive 300 mg GSK3228836 once weekly for 12 weeks along with LD of 300 mg GSK3228836 on Day 4 and Day 11 followed by step-down in dose of 150 mg GSK3228836 once weekly for 12 weeks along with placebo to match to maintain participant blinding.
Receives: Drug: GSK3228836; Drug: Placebo
Cohort 2: GSK3228836 300 mg + LD/ PlaceboExperimentalEligible participants not currently on nucleos(t)ide therapy will receive 300 mg GSK3228836 once weekly for 12 weeks along with LD of 300 mg GSK3228836 on Day 4 and Day 11 followed by placebo once weekly for 12 weeks.
Receives: Drug: GSK3228836; Drug: Placebo
Cohort 2: Placebo/ GSK3228836 300 mg + Placebo LDExperimentalEligible participants not currently on nucleos(t)ide therapy will receive placebo once weekly for 12 weeks followed by 300 mg GSK3228836 once weekly for 12 weeks along with placebo LD to match on Day 4 and Day 11.
Receives: Drug: GSK3228836; Drug: Placebo

What is being measured

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

  1. Number of Participants Achieving Sustained Virologic Response (SVR)

    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.

    Measured: Up to Week 48

Secondary outcomes (21)

  1. Number of Participants Achieving HBsAg and HBV DNA<LLOQ

    Participants achieving HBsAg and HBV DNA levels <LLOQ at the end of treatment (EOT) were reported.

    Measured: Up to Week 26

  2. Number 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).

    Measured: At Baseline and Week 24

  3. Number of Participants With Categorical Changes From Baseline in HBV DNA Values

    Participants who achieved a decline in HBV DNA values from baseline were reported. Participants were categorized in the following categorical HBV DNA decline of <1, >=1, >=2, and >=3 log IU/mL.

    Measured: At Baseline and Week 24

  4. 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.

    Participants who achieved ALT normalization were reported.

    Measured: At Baseline and Week 24

  5. Median Time to ALT Normalization

    Time to ALT normalization (ALT≤ULN) in the absence of rescue medication in participants with baseline ALT>ULN. Numbers of participants analyzed at Week 24 include participants with baseline ALT >ULN, and are as follows for NA therapy population: n=6 in GSK3228836 for 24 WK, n= 7 in GSK3228836 for 12 WK+12 WK, n=6 in GSK3228836 for 12 WK + Placebo for 12 WK, n=2 in Placebo for 12 WK + GSK3228836 for 12 WK, respectively. The numbers of participants analyzed are as follows for the not on NA therapy population: n=20 GSK3228836 for 24 WK, n=20 in GSK3228836 for 12 WK+12 WK, n=21 in GSK3228836 for 12 WK + Placebo for 12 WK, n=9 in Placebo for 12 WK + GSK3228836 for 12 WK arm, respectively.

    Measured: Baseline and up to Week 48

  6. Number of Participants With Positive Hepatitis B Virus E-antibody (HBeAb)

    Blood samples were collected to assess HBeAb level and participants with positive HBeAb were reported.

    Measured: Up to Week 48

  7. Mean HBsAg and HBV DNA Level

    Blood samples were collected from participants to assess HBsAg and HBV DNA level at indicated time points.

    Measured: At Baseline, Week 12, and 24

  8. Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level

    Blood samples were collected from participants to assess HBeAg level at indicated time points. Participants with presence of HBeAg at baseline were analyzed at indicated timepoint. Note: The units are on the log10 scale so negative values are expected (e.g. 0.933 U/mL = -0.03 log10 U/mL).

    Measured: At Baseline, Week 12, and 24

  9. Mean Change From Baseline in HBsAg and HBV DNA Level

    Blood samples were collected from participants to assess HBsAg and HBV DNA level at indicated time points. Note: The units are on the log10 scale so negative values are expected (e.g. 0.933 IU/mL = -0.03 log10 IU/mL).

    Measured: At Baseline, Week 12, and 24

  10. Mean Change From Baseline in HBeAg Level

    Blood samples were collected from participants to assess HBeAg level at indicated time points. Participants with presence of HBeAg at baseline were analyzed at indicated timepoint. Note: The units are on the log10 scale so negative values are expected (e.g. 0.933 U/mL = -0.03 log10 U/mL).

    Measured: At Baseline, Week 12, and 24

  11. Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level

    Blood samples were collected to assess anti-HBsAg level at indicated timepoints.

    Measured: At Baseline, Week 36, and 48

  12. Mean Change From Baseline in Anti-HBsAg Level

    Blood samples were collected to assess anti-HBsAg level at indicated timepoints.

    Measured: At Baseline, Week 12, and 24

  13. Mean Area Under the Concentration-time Curve From Time 0 up to 24 Hours (AUC0-24h) of GSK3228836

    Intensive pharmacokinetic (PK) sampling was done in a subset of participants on stable NA therapy to analyze AUC0-24h of GSK3228836.

    Measured: Up to Week 24

  14. Mean Maximum Observed Concentration (Cmax) of GSK3228836

    Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze Cmax of GSK3228836.

    Measured: Up to Week 24

  15. Median Time of Maximum Observed Concentration (Tmax) of GSK3228836

    Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze tmax of GSK3228836.

    Measured: Up to Week 24

  16. Mean AUC0-24h of NA Therapies

    Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze AUC0-24h. Participants on NA therapy were stratified as per the following NA therapy Tenofovir disoproxil fumarate 245 or 300 mg once daily, Tenofovir alafenamide 25 mg once a daily or every 2 days, and Entecavir 0.5 mg once daily.

    Measured: Up to Week 24

  17. Mean Ctau of NA Therapies

    Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze Ctau. Participants on NA therapy were stratified as per the following NA therapy Tenofovir disoproxil fumarate 245 or 300 mg once daily, Tenofovir alafenamide 25 mg once a daily or every 2 days, and Entecavir 0.5 mg once daily.

    Measured: Up to Week 24

  18. Mean Cmax of NA Therapies

    Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze Cmax. Participants on NA therapy were stratified as per the following NA therapy Tenofovir disoproxil fumarate 245 or 300 mg once daily, Tenofovir alafenamide 25 mg once a daily or every 2 days, and Entecavir 0.5 mg once daily.

    Measured: Up to Week 24

  19. Median Tmax of NA Therapies

    Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze tmax. Participants on NA therapy were stratified as per the following NA therapy Tenofovir disoproxil fumarate 245 or 300 mg once daily, Tenofovir alafenamide 25 mg once a daily or every 2 days, and Entecavir 0.5 mg once daily.

    Measured: Up to Week 24

  20. Median Terminal Half-life (t1/2) of GSK3228836

    Blood samples were collected from all participants for t1/2 analysis of GSK3228836. Note: for this endpoint data for more comparable arms GSK3228836 for 24WK and 12+12 WK from both on NA and not on NA therapy were presented.

    Measured: Up to Week 48

  21. Mean Ctau of GSK3228836

    Blood samples were collected from all participants for Ctau analysis of GSK3228836 at indicated. Note: for this endpoint data for more comparable arms GSK3228836 for 24WK and 12+12 WK from both on NA and not on NA therapy were presented.

    Measured: Up to Week 24

Timeline

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

  1. First posted26 Jun 2020
  2. Study start27 Jul 2020
  3. Primary completion18 Mar 2022
  4. Study completion18 Mar 2022

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 with CHB will be divided into two different cohorts; participants on stable nucleos(t)ide treatment and participants not currently on nucleos(t)ide therapy. For each cohort, participants will be randomized into one of the 4 different parallel arms to receive treatment.
Masking
Single blind
Who is masked
Participant
Enrolment
457 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04449029
Sponsor's protocol ID
209668
Acronym
B-Clear
Status last verified
Apr 2023
First submitted
23 Jun 2020
Last updated
16 May 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Yuen MF, Lim SG, Plesniak R, Tsuji K, Janssen HLA, Pojoga C, Gadano A, Popescu CP, Stepanova T, Asselah T, Diaconescu G, Yim HJ, Heo J, Janczewska E, Wong A, Idriz N, Imamura M, Rizzardini G, Takaguchi K, Andreone P, Arbune M, Hou J, Park SJ, Vata A, Cremer J, Elston R, Lukic T, Quinn G, Maynard L, Kendrick S, Plein H, Campbell F, Paff M, Theodore D; B-Clear Study Group. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. N Engl J Med. 2022 Nov 24;387(21):1957-1968. doi: 10.1056/NEJMoa2210027. Epub 2022 Nov 8.

    PubMed 36346079

  • 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

  • Han K, Youssef AS, Magee M, Hood S, Tracey H, Kwoh J, Theodore D, Paff M, Nader A. Lack of Pharmacokinetic Drug-Drug Interactions Between Bepirovirsen and Nucleos(t)ide Analogs. Clin Pharmacol Drug Dev. 2025 Apr;14(4):281-291. doi: 10.1002/cpdd.1518. Epub 2025 Feb 14.

    PubMed 39950613

  • Cremer J, Elston R, Campbell FM, Kendrick S, Paff M, Quinn G, Theodore D. B-Clear Phase 2b Study Design: Establishing the Efficacy and Safety of Bepirovirsen in Patients with Chronic Hepatitis B Virus Infection. Adv Ther. 2023 Sep;40(9):4101-4110. doi: 10.1007/s12325-023-02531-z. Epub 2023 Jul 1.

    PubMed 37393402

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 121 sites in 22 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 9 inclusion and 19 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 16 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 121 sites in Japan, Russia, South Korea, United States, China and 17 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 16 May 2023). 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?

Number of Participants Achieving Sustained Virologic Response (SVR) (time frame: Up to Week 48). 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 NCT04449029, which also lists 4 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 16 May 2023.

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