Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants With Chronic Hepatitis B (B-Well 1)

NCT ID: NCT05630807

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 981 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-07
• Study Completion Date: 2026-05-05

Brief Summary

This study is intended to confirm the efficacy, safety, pharmacokinetic (PK) profile, and the durability of hepatitis B virus surface antigen (HBsAg) suppression observed with bepirovirsen for 24 weeks (with loading doses) as compared to the placebo arm. This study will have 4 stages: a) Double-blind treatment (bepirovirsen or placebo) for 24 weeks. b) Nucleos(t)ide analogue (NA) treatment for 24 weeks. c) NA cessation stage OR Continue NA for 24 weeks. d) Durability of response and follow up for further 24 weeks for participants who stopped NA treatment at Week 48. The arms will be stratified based on HBsAg level (HBsAg greater than or equal to [≥] 100 international unit per milliliter [IU/mL] to less than or equal [≤]1000 IU/mL or greater than [>] 1000 IU/mL to ≤3000 IU/mL) at screening. The total duration of the study, including screening (up to 60 days), the double-blind treatment stage (24 weeks), the On NA only stage (24 weeks), and the NA cessation and durability stages (48 weeks) is up to approximately 104 weeks at maximum for each participant.

Conditions

Chronic Hepatitis B; Hepatitis B, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Bepirovirsen

Group Type: EXPERIMENTAL

Bepirovirsen

Intervention Type: DRUG

Bepirovirsen will be administered.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Matching placebo will be administered.

Interventions

Bepirovirsen

Bepirovirsen will be administered.

Intervention Type: DRUG

Placebo

Matching placebo will be administered.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Participants who have documented chronic HBV infection ≥6 months prior to screening and currently receiving stable NA therapy 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 IU/mL, but no greater than ≤3000 IU/mL.
• Plasma or serum HBV DNA concentration must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL.
• Alanine aminotransferase (ALT) ≤2 × upper limit of normal (ULN).
• Participants who are willing and able to cease their NA treatment in accordance with the protocol.

Exclusion Criteria

• 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:

a) Current history of Hepatitis C infection or participants that have been cured for <12 months at the time of screening b) Human immunodeficiency virus (HIV), c) Hepatitis D virus.

• History of or suspected liver cirrhosis and/or evidence of cirrhosis.
• Diagnosed or suspected hepatocellular carcinoma.
• History of malignancy within the past 5 years except for 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) current or history of an autoimmune condition 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).
• History of alcohol or drug abuse/dependence.
• 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 to whom immunosuppressive treatment, including therapeutic doses of steroids is contraindicated, should not be considered for enrolment in the study.
• Currently taking, or has taken within 12 months of Screening, any interferon containing therapy.
• Participants requiring anti coagulation therapies (e.g., warfarin, Factor Xa inhibitors) or anti-platelet agents (like clopidogrel or aspirin) unless treatment can safely be discontinued throughout duration of the study, by the discretion of the investigator. Occasional use is permitted.
• Prior treatment with any oligonucleotide or siRNA within 12 months prior to the first dosing day.
• Prior treatment with bepirovirsen.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Chandler, Arizona, United States

GSK Investigational Site

Davis, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Palo Alto, California, United States

GSK Investigational Site

San Jose, California, United States

GSK Investigational Site

Littleton, Colorado, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Iowa City, Iowa, United States

GSK Investigational Site

Baltimore, Maryland, United States

GSK Investigational Site

Detroit, Michigan, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Capital Federal, , Argentina

GSK Investigational Site

Pilar, , Argentina

GSK Investigational Site

Rosario, , Argentina

GSK Investigational Site

Aracaju, , Brazil

GSK Investigational Site

Campinas, , Brazil

GSK Investigational Site

Curitiba, , Brazil

GSK Investigational Site

Manaus, , Brazil

GSK Investigational Site

Porto Alegre, , Brazil

GSK Investigational Site

Santa Maria, , Brazil

GSK Investigational Site

São Paulo, , Brazil

GSK Investigational Site

São Paulo, , Brazil

GSK Investigational Site

Vila Mariana, , Brazil

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Veliko Tarnovo, , Bulgaria

GSK Investigational Site

Vancouver, British Columbia, Canada

GSK Investigational Site

Victoria, British Columbia, Canada

GSK Investigational Site

Ottawa, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Saint-Jérôme, Quebec, Canada

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Changchun, , China

GSK Investigational Site

Chengdu, , China

GSK Investigational Site

Chongqing, , China

GSK Investigational Site

Fuzhou, , China

GSK Investigational Site

Guangzhou, , China

GSK Investigational Site

Guangzhou, , China

GSK Investigational Site

Guangzhou, , China

GSK Investigational Site

Hangzhou, , China

GSK Investigational Site

Hangzhou, , China

GSK Investigational Site

Kunming, , China

GSK Investigational Site

Nanjing, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Shenyang, , China

GSK Investigational Site

Shenzhen, , China

GSK Investigational Site

Ürümqi, , China

GSK Investigational Site

Wuhan, , China

GSK Investigational Site

Xi'an, , China

GSK Investigational Site

Zhengzhou, , China

GSK Investigational Site

Zhenjiang, , China

GSK Investigational Site

Clermont-Ferrand, , France

GSK Investigational Site

Clichy, , France

GSK Investigational Site

Dijon, , France

GSK Investigational Site

Lille, , France

GSK Investigational Site

Pessac, , France

GSK Investigational Site

Poitiers, , France

GSK Investigational Site

Rennes, , France

GSK Investigational Site

Strasbourg, , France

GSK Investigational Site

Toulouse, , France

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Bochum, , Germany

GSK Investigational Site

Cologne, , Germany

GSK Investigational Site

Düsseldorf, , Germany

GSK Investigational Site

München, , Germany

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Periohi Dragana Alexand, , Greece

GSK Investigational Site

Rio Patras, , Greece

GSK Investigational Site

Kowloon, , Hong Kong

GSK Investigational Site

Pokfulam, , Hong Kong

GSK Investigational Site

Shatin, , Hong Kong

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Eger, , Hungary

GSK Investigational Site

Gyula, , Hungary

GSK Investigational Site

Miskolc, , Hungary

GSK Investigational Site

Belagavi, , India

GSK Investigational Site

Chandigarh, , India

GSK Investigational Site

Chennai, , India

GSK Investigational Site

Coimbatore, , India

GSK Investigational Site

Guhawati, , India

GSK Investigational Site

Hyderabad, , India

GSK Investigational Site

HyderabadTelangana, , India

GSK Investigational Site

Jaipur, , India

GSK Investigational Site

Ludhiana, , India

GSK Investigational Site

Manipal, , India

GSK Investigational Site

Mumbai, , India

GSK Investigational Site

Mumbai, , India

GSK Investigational Site

Mumbai, , India

GSK Investigational Site

Pune, , India

GSK Investigational Site

Surat, , India

GSK Investigational Site

Brescia, , Italy

GSK Investigational Site

Foggia, , Italy

GSK Investigational Site

Messina, , Italy

GSK Investigational Site

Milan, , Italy

GSK Investigational Site

Milan, , Italy

GSK Investigational Site

Modena, , Italy

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Ehime, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Gifu, , Japan

GSK Investigational Site

Gifu, , Japan

GSK Investigational Site

Hiroshima, , Japan

GSK Investigational Site

Hiroshima, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Hyōgo, , Japan

GSK Investigational Site

Kumamoto, , Japan

GSK Investigational Site

Miyagi, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

George Town, , Malaysia

GSK Investigational Site

Johor Bahru, , Malaysia

GSK Investigational Site

Kota Bharu Kelantan, , Malaysia

GSK Investigational Site

Kota Kinabalu, , Malaysia

GSK Investigational Site

Kuala Lumpur, , Malaysia

GSK Investigational Site

Kuantan, , Malaysia

GSK Investigational Site

Guadalajara, , Mexico

GSK Investigational Site

Oaxaca City, , Mexico

GSK Investigational Site

Panama City, , Panama

GSK Investigational Site

Bytom, , Poland

GSK Investigational Site

Krakow, , Poland

GSK Investigational Site

Łańcut, , Poland

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Cluj-Napoca, , Romania

GSK Investigational Site

Iași, , Romania

GSK Investigational Site

Suceava, , Romania

GSK Investigational Site

Timișoara, , Romania

GSK Investigational Site

Singapore, , Singapore

GSK Investigational Site

Singapore, , Singapore

GSK Investigational Site

Ansan, , South Korea

GSK Investigational Site

Busan, , South Korea

GSK Investigational Site

Daegu, , South Korea

GSK Investigational Site

Daegu, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

León, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Málaga, , Spain

GSK Investigational Site

Salamanca, , Spain

GSK Investigational Site

Santander, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Valladolid, , Spain

GSK Investigational Site

Vigo, , Spain

GSK Investigational Site

Kaohsiung City, , Taiwan

GSK Investigational Site

Kaohsiung City, , Taiwan

GSK Investigational Site

Taichung, , Taiwan

GSK Investigational Site

Taipei, , Taiwan

GSK Investigational Site

Tau-Yuan, , Taiwan

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Ankara, , Turkey (Türkiye)

GSK Investigational Site

Birmingham, , United Kingdom

GSK Investigational Site

Edinburgh, , United Kingdom

GSK Investigational Site

Leeds West Yorkshire, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

Countries

United States; Argentina; Brazil; Bulgaria; Canada; China; France; Germany; Greece; Hong Kong; Hungary; India; Italy; Japan; Malaysia; Mexico; Panama; Poland; Romania; Singapore; South Korea; Spain; Taiwan; Thailand; Turkey (Türkiye); United Kingdom

Other Identifiers

2021-005139-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

202009

Identifier Type: -

Identifier Source: org_study_id