Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants With Chronic Hepatitis B (B-Well 2)

NCT ID: NCT05630820

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 857 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-06
• Study Completion Date: 2026-04-29

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) 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

Makati City, , Philippines

GSK Investigational Site

Pasig, , Philippines

GSK Investigational Site

Silang, , Philippines

GSK Investigational Site

Gdansk, , Poland

GSK Investigational Site

Mysłowice, , Poland

GSK Investigational Site

Żychlin, , Poland

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Cluj-Napoca, , Romania

GSK Investigational Site

Constanța, , Romania

GSK Investigational Site

Galati, , Romania

GSK Investigational Site

Oradea, , Romania

GSK Investigational Site

Ansan, , South Korea

GSK Investigational Site

Incheon, , South Korea

GSK Investigational Site

Pusan, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Ulsan, , South Korea

GSK Investigational Site

Alcorcon Madrid, , Spain

GSK Investigational Site

Badajoz, , Spain

GSK Investigational Site

Granada, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Sabadell Barcelona, , Spain

GSK Investigational Site

Seville, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Valladolid, , Spain

GSK Investigational Site

Zaragoza, , Spain

GSK Investigational Site

Kaohsiung City, , Taiwan

GSK Investigational Site

Taichung, , Taiwan

GSK Investigational Site

Tainan, , Taiwan

GSK Investigational Site

Taipei, , Taiwan

GSK Investigational Site

Chiang Mai, , Thailand

GSK Investigational Site

Ankara, , Turkey (Türkiye)

GSK Investigational Site

Istanbul, , Turkey (Türkiye)

GSK Investigational Site

Izmir, , Turkey (Türkiye)

GSK Investigational Site

Liverpool, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Middlesbrough, , United Kingdom

GSK Investigational Site

Newcastle upon Tyne, , United Kingdom

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Changchun, , China

GSK Investigational Site

Chengdu, , China

GSK Investigational Site

Chongqing, , China

GSK Investigational Site

Guangzhou, , China

GSK Investigational Site

Guangzhou, , China

GSK Investigational Site

Hangzhou, , China

GSK Investigational Site

Hangzhou, , China

GSK Investigational Site

Hefei, , China

GSK Investigational Site

Kunming, , China

GSK Investigational Site

Liuchow, , China

GSK Investigational Site

Nanjing, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Shenzhen, , China

GSK Investigational Site

Taiyuan, , China

GSK Investigational Site

Tianjin, , China

GSK Investigational Site

Ürümqi, , China

GSK Investigational Site

Wuhan, , China

GSK Investigational Site

Xi'an, , China

GSK Investigational Site

Xiamen, , China

GSK Investigational Site

Zhengzhou, , China

GSK Investigational Site

Zunyi, , China

GSK Investigational Site

Créteil, , France

GSK Investigational Site

Grenoble, , France

GSK Investigational Site

Limoges, , France

GSK Investigational Site

Lyon, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Rouen, , France

GSK Investigational Site

Toulouse, , France

GSK Investigational Site

Frankfurt, , Germany

GSK Investigational Site

Frankfurt, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Hanover, , Germany

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Heraklion Crete, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Szeged, , Hungary

GSK Investigational Site

Székesfehérvár, , Hungary

GSK Investigational Site

Zalaegerszeg, , Hungary

GSK Investigational Site

Ahmedabad, , India

GSK Investigational Site

Chennai, , India

GSK Investigational Site

Kanpur, , India

GSK Investigational Site

Kochi, , India

GSK Investigational Site

Kolkata, , India

GSK Investigational Site

Kolkata, , India

GSK Investigational Site

Mumbai, , India

GSK Investigational Site

Mumbai, , India

GSK Investigational Site

Nagpur, , India

GSK Investigational Site

New Delhi, , India

GSK Investigational Site

New Delhi, , India

GSK Investigational Site

New Delhi, , India

GSK Investigational Site

Pune, , India

GSK Investigational Site

Raipur, , India

GSK Investigational Site

Secunderabad, , India

GSK Investigational Site

Milan, , Italy

GSK Investigational Site

Napoli, , Italy

GSK Investigational Site

Padua, , Italy

GSK Investigational Site

Palermo, , Italy

GSK Investigational Site

Pisa, , Italy

GSK Investigational Site

Roma, , Italy

GSK Investigational Site

Sassari, , Italy

GSK Investigational Site

Torino, , Italy

GSK Investigational Site

Fukui, , Japan

GSK Investigational Site

Hiroshima, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Ishikawa, , Japan

GSK Investigational Site

Kagawa, , Japan

GSK Investigational Site

Kumamoto, , Japan

GSK Investigational Site

Nagasaki, , Japan

GSK Investigational Site

Nara, , Japan

GSK Investigational Site

Niigata, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Yamaguchi, , Japan

GSK Investigational Site

Yamanashi, , Japan

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

Kuala Terengganu, , Malaysia

GSK Investigational Site

Kuantan, , Malaysia

GSK Investigational Site

Aguascalientes, , Mexico

GSK Investigational Site

Auckland, , New Zealand

GSK Investigational Site

Papatoetoe Auckland, , New Zealand

GSK Investigational Site

Panama City, , Panama

GSK Investigational Site

Cebu City, , Philippines

GSK Investigational Site

Rio de Janeiro, , Brazil

GSK Investigational Site

Salvador, , Brazil

GSK Investigational Site

Vitória, , Brazil

GSK Investigational Site

Plovdiv, , Bulgaria

GSK Investigational Site

Sliven, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Varna, , Bulgaria

GSK Investigational Site

Calgary, Alberta, Canada

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

Halifax, Nova Scotia, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Regina, Saskatchewan, Canada

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Centreville, Alabama, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

San Francisco, California, United States

GSK Investigational Site

San Francisco, California, United States

GSK Investigational Site

Colorado Springs, Colorado, United States

GSK Investigational Site

Ft. Pierce, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Glen Burnie, Maryland, United States

GSK Investigational Site

Minneapolis, Minnesota, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Denison, Texas, United States

GSK Investigational Site

Seattle, Washington, United States

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Ciudad Autonoma de Bueno, , Argentina

GSK Investigational Site

Santa Fe, , Argentina

GSK Investigational Site

Westmead, New South Wales, Australia

GSK Investigational Site

Herston, Queensland, Australia

GSK Investigational Site

Box Hill, Victoria, Australia

GSK Investigational Site

Fitzroy, Victoria, Australia

GSK Investigational Site

Botucatu, , Brazil

GSK Investigational Site

Fortaleza, , Brazil

GSK Investigational Site

Nova Iguaçu, , Brazil

GSK Investigational Site

Porto Alegre, , Brazil

GSK Investigational Site

Porto Alegre, , Brazil

Countries

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

Other Identifiers

2022-002268-53

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

219288

Identifier Type: -

Identifier Source: org_study_id