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

NCT04449029 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 209668
• Study Type: interventional
• Target: 457
• Locations: 22 countries
• Sites: 121

Brief 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. 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

Keywords

Chronic Hepatitis B; GSK3228836; Hepatitis B virus surface antigen; Nucleos(t)ide therapy; Sustained virologic response

Outcome Measures

Primary Outcomes (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.

  Up to Week 48

Secondary Outcomes (21)

• Number of Participants Achieving HBsAg and HBV DNA<LLOQ

  Up to Week 26

• Number of Participants With Categorical Changes From Baseline in HBsAg Values

  At Baseline and Week 24

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

  At Baseline and Week 24

• Number of Participants With Alanine Aminotransferase (ALT) Normalization

  At Baseline and Week 24

• Median Time to ALT Normalization

  Baseline and up to Week 48

Study Arms (8)

Cohort 1: GSK3228836 300 mg + LD

EXPERIMENTAL

Eligible 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.

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

Cohort 1: GSK3228836 300 mg + LD/ GSK3228836 150 mg + Placebo

EXPERIMENTAL

Eligible 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.

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

Cohort 1: GSK3228836 300 mg + LD/ Placebo

EXPERIMENTAL

Eligible 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.

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

Cohort 1: Placebo/ GSK3228836 300 mg + Placebo LD

EXPERIMENTAL

Eligible 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.

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

Cohort 2: GSK3228836 300 mg + LD

EXPERIMENTAL

Eligible 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.

Drug: GSK3228836

Cohort 2: GSK3228836 300 mg + LD/ GSK3228836 150 mg + Placebo

EXPERIMENTAL

Eligible 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.

Drug: GSK3228836; Drug: Placebo

Cohort 2: GSK3228836 300 mg + LD/ Placebo

EXPERIMENTAL

Eligible 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.

Drug: GSK3228836; Drug: Placebo

Cohort 2: Placebo/ GSK3228836 300 mg + Placebo LD

EXPERIMENTAL

Eligible 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.

Drug: GSK3228836; Drug: Placebo

Interventions

GSK3228836 DRUG

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.

Cohort 1: GSK3228836 300 mg + LD; Cohort 1: GSK3228836 300 mg + LD/ GSK3228836 150 mg + Placebo; Cohort 1: GSK3228836 300 mg + LD/ Placebo; Cohort 1: Placebo/ GSK3228836 300 mg + Placebo LD; Cohort 2: GSK3228836 300 mg + LD; Cohort 2: GSK3228836 300 mg + LD/ GSK3228836 150 mg + Placebo; Cohort 2: GSK3228836 300 mg + LD/ Placebo; Cohort 2: Placebo/ GSK3228836 300 mg + Placebo LD

Placebo DRUG

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

Cohort 1: GSK3228836 300 mg + LD/ GSK3228836 150 mg + Placebo; Cohort 1: GSK3228836 300 mg + LD/ Placebo; Cohort 1: Placebo/ GSK3228836 300 mg + Placebo LD; Cohort 2: GSK3228836 300 mg + LD/ GSK3228836 150 mg + Placebo; Cohort 2: GSK3228836 300 mg + LD/ Placebo; Cohort 2: Placebo/ GSK3228836 300 mg + Placebo LD

Nucleos(t)ide therapy DRUG

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

Cohort 1: GSK3228836 300 mg + LD; Cohort 1: GSK3228836 300 mg + LD/ GSK3228836 150 mg + Placebo; Cohort 1: GSK3228836 300 mg + LD/ Placebo; Cohort 1: Placebo/ GSK3228836 300 mg + Placebo LD

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed informed consent.

You may not qualify if:

• Clinically significant abnormalities, aside from chronic HBV infection in medical history (e.g., moderate-severe liver disease other than chronic HBV, acute coronary syndrome within 6 months of screening, major surgery within 3 months of screening, significant/unstable cardiac disease, uncontrolled diabetes, bleeding diathesis or coagulopathy) or physical examination.
• Co-infection with Current or past history of Hepatitis C virus (HCV), Human immunodeficiency virus (HIV), Hepatitis D virus (HDV).
• 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).
• History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension).
• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (121)

GSK Investigational Site

Los Angeles, California, 90089, United States

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GSK Investigational Site

Miami, Florida, 33125, United States

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GSK Investigational Site

Miami, Florida, 33136, United States

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GSK Investigational Site

Decatur, Georgia, 30033, United States

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GSK Investigational Site

Boston, Massachusetts, 02114, United States

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GSK Investigational Site

New York, New York, 10016, United States

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GSK Investigational Site

Pittsburgh, Pennsylvania, 15213, United States

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GSK Investigational Site

Richmond, Virginia, 23249, United States

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GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1181ACH, Argentina

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GSK Investigational Site

Buenos Aires, C1280AEB, Argentina

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GSK Investigational Site

Sliven, 8800, Bulgaria

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GSK Investigational Site

Sofia, 1431, Bulgaria

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GSK Investigational Site

Sofia, 1463, Bulgaria

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GSK Investigational Site

Sofia, 1527, Bulgaria

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GSK Investigational Site

Calgary, Alberta, T2N 4Z6, Canada

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GSK Investigational Site

Victoria, British Columbia, V8V 3M9, Canada

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GSK Investigational Site

London, Ontario, N6A 2C2, Canada

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GSK Investigational Site

Toronto, Ontario, M5G 2C4, Canada

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GSK Investigational Site

Montreal, Quebec, H2L 4E9, Canada

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Regina, Saskatchewan, S4P 0W5, Canada

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Québec, G1V 4G2, Canada

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GSK Investigational Site

Wuhan, Hubei, 430030, China

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GSK Investigational Site

Shenyang, Liaoning, 110022, China

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GSK Investigational Site

Chongqing, Sichuan, 400042, China

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GSK Investigational Site

Beijing, 100015, China

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GSK Investigational Site

Beijing, 100034, China

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GSK Investigational Site

Beijing, 100050, China

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GSK Investigational Site

Guangzhou, 510000, China

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GSK Investigational Site

Shanghai, 200025, China

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GSK Investigational Site

Clichy, 92118, France

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GSK Investigational Site

Créteil, 94010, France

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GSK Investigational Site

Limoges, 87042, France

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GSK Investigational Site

Lyon, 69317, France

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GSK Investigational Site

Nice, 06202, France

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Strasbourg, 67200, France

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GSK Investigational Site

Erlangen, Bavaria, 91054, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60590, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

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GSK Investigational Site

Berlin, 10439, Germany

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GSK Investigational Site

Hamburg, 20146, Germany

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GSK Investigational Site

Pokfulam, Hong Kong

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GSK Investigational Site

Modena, Emilia-Romagna, 41126, Italy

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GSK Investigational Site

Milan, Lombardy, 20122, Italy

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GSK Investigational Site

Milan, Lombardy, 20132, Italy

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GSK Investigational Site

Milan, Lombardy, 20157, Italy

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GSK Investigational Site

Ehime, 790-8524, Japan

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GSK Investigational Site

Hiroshima, 730-8619, Japan

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GSK Investigational Site

Hiroshima, 734-8551, Japan

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GSK Investigational Site

Hokkaido, 080-0024, Japan

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GSK Investigational Site

Ishikawa, 920-8650, Japan

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GSK Investigational Site

Ishikawa, 924-8588, Japan

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GSK Investigational Site

Kagawa, 760-8557, Japan

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GSK Investigational Site

Kumamoto, 860-8556, Japan

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GSK Investigational Site

Kumamoto, 862-8655, Japan

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GSK Investigational Site

Miyagi, 980-8574, Japan

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GSK Investigational Site

Nagasaki, 856-8562, Japan

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GSK Investigational Site

Osaka, 565-0871, Japan

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GSK Investigational Site

Tokyo, 113-8603, Japan

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GSK Investigational Site

Tokyo, 180-8610, Japan

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GSK Investigational Site

Kuala Lumpur, 59100, Malaysia

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Makati City, 1229, Philippines

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Quezon City, 1101, Philippines

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Lublin, 20-884, Poland

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Mysłowice, 41-400, Poland

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Warsaw, 00-332, Poland

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Łańcut, 37-100, Poland

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GSK Investigational Site

Brasov, 500283, Romania

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Bucharest, 030303, Romania

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GSK Investigational Site

Cluj-Napoca, 400139, Romania

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GSK Investigational Site

Cluj-Napoca, 400162, Romania

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Craiova, 200515, Romania

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Galati, 800179, Romania

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Iași, 700116, Romania

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GSK Investigational Site

Timișoara, 300310, Romania

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GSK Investigational Site

Chelyabinsk, 454052, Russia

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Kaliningrad, 236016, Russia

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GSK Investigational Site

Krasnodar, 350000, Russia

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GSK Investigational Site

Moscow, 121170, Russia

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GSK Investigational Site

Moscow, 125008, Russia

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Novosibirsk, 630005, Russia

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GSK Investigational Site

Novosibirsk, 630099, Russia

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GSK Investigational Site

Saint Petersburg, 190103, Russia

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Saint Petersburg, 191167, Russia

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GSK Investigational Site

Samara, 443063, Russia

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GSK Investigational Site

Красноярск, 660049, Russia

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GSK Investigational Site

Singapore, 119074, Singapore

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Singapore, 169608, Singapore

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Singapore, 529889, Singapore

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Port Elizabeth, Eastern Cape, 6001, South Africa

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GSK Investigational Site

Ennerdale, Gauteng, 1830, South Africa

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GSK Investigational Site

Lenasia Johannesburg, Gauteng, 1827, South Africa

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Durban, KwaZulu-Natal, 4052, South Africa

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GSK Investigational Site

Kwaguqa Emalahleni, Mpumalanga, 1039, South Africa

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GSK Investigational Site

Vosloorus Ext 2, 1475, South Africa

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GSK Investigational Site

Busan, 47392, South Korea

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GSK Investigational Site

Busan, 49241, South Korea

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GSK Investigational Site

Daegu, 41944, South Korea

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GSK Investigational Site

Gyeonggi-do, 15355, South Korea

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GSK Investigational Site

Incheon, 21565, South Korea

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GSK Investigational Site

Seoul, 03080, South Korea

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GSK Investigational Site

Seoul, 05505, South Korea

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GSK Investigational Site

Seoul, 06973, South Korea

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GSK Investigational Site

Ulsan, 44033, South Korea

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GSK Investigational Site

Barcelona, 08035, Spain

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GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Madrid, 28029, Spain

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GSK Investigational Site

Madrid, 28031, Spain

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GSK Investigational Site

Majadahonda (Madrid), 28222, Spain

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GSK Investigational Site

Málaga, 29010, Spain

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GSK Investigational Site

Santander, 39008, Spain

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GSK Investigational Site

Seville, 41013, Spain

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GSK Investigational Site

Changhua, 500, Taiwan

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Taichung, 40447, Taiwan

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GSK Investigational Site

Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Chiang Mai, 50200, Thailand

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GSK Investigational Site

Phitsanulok, 65000, Thailand

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GSK Investigational Site

Songkhla, 9110, Thailand

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GSK Investigational Site

London, WC1E 6JB, United Kingdom

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GSK Investigational Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

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GSK Investigational Site

Plymouth, PL6 8DH, United Kingdom

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Related Publications (3)

• 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.

  PMID: 36346079 BACKGROUND

• 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. 2025 Oct 3. doi: 10.1007/s12072-025-10917-0. Online ahead of print.

  PMID: 41042426 DERIVED

• 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.

  PMID: 37393402 DERIVED

MeSH Terms

Conditions

Hepatitis B; Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will be blinded to the study treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 23, 2020
• First Posted: June 26, 2020
• Study Start: July 27, 2020
• Primary Completion: March 18, 2022
• Study Completion: March 18, 2022
• Last Updated: May 16, 2023
• Results First Posted: May 16, 2023

Record last verified: 2023-04

Locations

IT (4); JP (14); MY (1); PH (2); RU (11); KR (9); CA (7); GB (3); AR (2); CN (8); ZA (6); RO (8); HK (1); SG (3); ES (8); DE (5); TW (2); BU (4); US (8); FR (6); PL (4); TH (5)