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

NCT05630820 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 2192882022-002268-53
• Study Type: interventional
• Target: 857
• Locations: 27 countries
• Sites: 171

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

Keywords

Hepatitis; Chronic Hepatitis; Chronic Hepatitis B; Hepatitis B Virus; hepatitis B virus e-antigen; Bepirovirsen; Nucleos(t)ide analog; Antisense Oligonucleotide; 202009; 219288; Nucleos(t)ide analogue

Outcome Measures

Primary Outcomes (1)

• Number of participants achieving functional cure (FC) with baseline HBsAg ≤3000 IU/mL

  The number of participants who achieved FC after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication will be reported. The FC for HBV is defined as Sustained suppression (24 weeks or longer) of HBV DNA \<Lower limit of quantification (LLOQ) off all HBV treatment and HBsAg not detected with or without HBsAb after a finite duration of therapy.

  Up to 72 weeks

Secondary Outcomes (3)

• Number of participants achieving FC with baseline HBsAg ≤1000 IU/mL

  Up to 72 weeks

• Number of participants achieving sustained suppression of HBV DNA (<LLOQ) with baseline HBsAg ≤3000 IU/mL

  Up to 72 weeks

• Number of participants achieving sustained suppression of HBV DNA (<LLOQ) with baseline HBsAg ≤1000 IU/mL

  Up to 72 weeks

Study Arms (2)

Bepirovirsen

EXPERIMENTAL

Drug: Bepirovirsen

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Bepirovirsen DRUG

Bepirovirsen will be administered.

Bepirovirsen

Placebo OTHER

Matching placebo will be administered.

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

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:
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (171)

GSK Investigational Site

Centreville, Alabama, 35042, United States

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GSK Investigational Site

Los Angeles, California, 90033, United States

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San Francisco, California, 94115, United States

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San Francisco, California, 94121, United States

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Colorado Springs, Colorado, 80907, United States

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Ft. Pierce, Florida, 34982, United States

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Miami, Florida, 33136, United States

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Glen Burnie, Maryland, 21061, United States

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Minneapolis, Minnesota, 55404, United States

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Philadelphia, Pennsylvania, 19104, United States

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Denison, Texas, 75020, United States

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Seattle, Washington, 98104, United States

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Buenos Aires, 1023, Argentina

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Buenos Aires, C1425AGC, Argentina

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Ciudad Autonoma de Bueno, C1056ABI, Argentina

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Santa Fe, 3000, Argentina

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Westmead, New South Wales, 2145, Australia

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Herston, Queensland, 4029, Australia

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Box Hill, Victoria, 3128, Australia

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Fitzroy, Victoria, 3065, Australia

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Botucatu, 18618-686, Brazil

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Fortaleza, 60430-372, Brazil

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Nova Iguaçu, 26030-380, Brazil

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Porto Alegre, 90020-090, Brazil

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Porto Alegre, 90035003, Brazil

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Rio de Janeiro, 21045-900, Brazil

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Salvador, 40110160, Brazil

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Vitória, 29043260, Brazil

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Plovdiv, 4002, Bulgaria

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Sliven, 8800, Bulgaria

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Sofia, 1797, Bulgaria

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Varna, 9020, Bulgaria

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Calgary, Alberta, T2N 4N1, Canada

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Edmonton, Alberta, T6G 2B7, Canada

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Edmonton, Alberta, T6G 2X8, Canada

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Halifax, Nova Scotia, B3H 2Y9, Canada

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Toronto, Ontario, M6H 3M1, Canada

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Montreal, Quebec, H2L 4E9, Canada

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Montreal, Quebec, H2L 4P9, Canada

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Regina, Saskatchewan, S4P 0W5, Canada

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Beijing, 100015, China

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Beijing, 100032, China

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Changchun, 130021, China

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Chengdu, 610072, China

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Chongqing, 400042, China

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Guangzhou, 510515, China

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Guangzhou, 510630, China

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Hangzhou, 310000, China

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Hangzhou, 310003, China

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Hefei, 230022, China

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Kunming, 650021, China

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Liuchow, China

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Nanjing, 210003, China

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Shanghai, 200025, China

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Shanghai, 200052, China

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Shenzhen, 518023, China

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Taiyuan, 030001, China

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Tianjin, 300000, China

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Ürümqi, 830054, China

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Wuhan, 430022, China

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Xi'an, 710061, China

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Xiamen, 361015, China

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Zhengzhou, 450000, China

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Zunyi, 563114, China

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Créteil, 94010, France

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Grenoble, 38043, France

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Limoges, 87042, France

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Lyon, 69317, France

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Paris, 75651, France

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Rouen, 76031, France

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Toulouse, 31059, France

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Frankfurt, 60329, Germany

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Frankfurt, 60596, Germany

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Hamburg, 20146, Germany

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Hanover, 30625, Germany

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Athens, 115 27, Greece

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Heraklion Crete, 715 00, Greece

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Thessaloniki, 54642, Greece

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Szeged, 6725, Hungary

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Székesfehérvár, 8000, Hungary

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Zalaegerszeg, Hungary

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Ahmedabad, 380009, India

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Chennai, 600035, India

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Kanpur, 208002, India

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Kochi, 682026, India

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Kolkata, 700150, India

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Kolkata, India

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Mumbai, 400012, India

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Mumbai, 400022, India

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Nagpur, 441108, India

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New Delhi, 110029, India

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New Delhi, 110060, India

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New Delhi, 110070, India

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Pune, 411001, India

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Raipur, India

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Secunderabad, 500003, India

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Milan, 20157, Italy

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Naples, 80131, Italy

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Padua, 35128, Italy

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Palermo, 90127, Italy

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Pisa, 56124, Italy

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Roma, 00133, Italy

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Sassari, 07100, Italy

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Torino, 10126, Italy

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Fukui, 918-8503, Japan

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Hiroshima, 730-8619, Japan

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Hokkaido, 006-8555, Japan

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Hokkaido, 060-8648, Japan

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Hokkaido, 062-8618, Japan

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Ishikawa, 920-8650, Japan

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Kagawa, 760-8557, Japan

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Kumamoto, 860-8556, Japan

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Nagasaki, 856-8562, Japan

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Nara, 634-8522, Japan

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Niigata, 950-1104, Japan

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Osaka, 565-0871, Japan

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Tokyo, 113-8603, Japan

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Yamaguchi, 750-0061, Japan

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Yamanashi, 409-3898, Japan

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Johor Bahru, 80100, Malaysia

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Kota Bharu Kelantan, Malaysia

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Kota Kinabalu, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Kuala Terengganu, 20400, Malaysia

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Kuantan, 25100, Malaysia

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Aguascalientes, 20010, Mexico

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Auckland, 1023, New Zealand

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Papatoetoe Auckland, 2025, New Zealand

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Panama City, Panama

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Cebu City, 6000, Philippines

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Makati City, 1229, Philippines

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Pasig, 1605, Philippines

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Silang, 4118, Philippines

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Gdansk, 80-405, Poland

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Mysłowice, 41-400, Poland

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Żychlin, 62-571, Poland

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Bucharest, 020475, Romania

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Bucharest, 030303, Romania

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Cluj-Napoca, 400348, Romania

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Constanța, 900709, Romania

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Galati, 800179, Romania

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GSK Investigational Site

Oradea, 410469, Romania

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GSK Investigational Site

Ansan, 15355, South Korea

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Incheon, 405-760, South Korea

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GSK Investigational Site

Pusan, 49241, South Korea

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GSK Investigational Site

Seoul, 03312, South Korea

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GSK Investigational Site

Seoul, 05505, South Korea

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GSK Investigational Site

Ulsan, 44033, South Korea

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GSK Investigational Site

Alcorcon Madrid, Spain

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GSK Investigational Site

Badajoz, 06080, Spain

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GSK Investigational Site

Granada, 18016, Spain

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GSK Investigational Site

Madrid, 28006, Spain

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GSK Investigational Site

Madrid, 28032, Spain

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GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

Sabadell Barcelona, 08208, Spain

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Seville, 41013, Spain

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Valencia, 46026, Spain

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Valladolid, 47012, Spain

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GSK Investigational Site

Zaragoza, 50009, Spain

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GSK Investigational Site

Kaohsiung City, 824, Taiwan

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Taichung, 404, Taiwan

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Tainan, 704, Taiwan

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GSK Investigational Site

Taipei, 100, Taiwan

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GSK Investigational Site

Chiang Mai, 50200, Thailand

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GSK Investigational Site

Ankara, 06590, Turkey (Türkiye)

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GSK Investigational Site

Istanbul, 34010, Turkey (Türkiye)

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GSK Investigational Site

Izmir, 35100, Turkey (Türkiye)

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Liverpool, L7 8XP, United Kingdom

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GSK Investigational Site

London, WC1E 6JB, United Kingdom

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GSK Investigational Site

Middlesbrough, TS4 3BW, United Kingdom

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GSK Investigational Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

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MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Hepatitis B

Condition Hierarchy (Ancestors)

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

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This will be a double blinded study in which investigators/site staff and the Sponsor will remain blinded to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multicenter, randomized, double-blind, placebo-controlled study.

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: November 30, 2022
• Study Start: December 6, 2022
• Primary Completion: November 3, 2025
• Study Completion: April 29, 2026
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

TH (1); PL (3); CN (24); TU (3); CA (8); GB (4); US (12); AR (4); NZ (2); RO (6); TW (4); GR (3); MY (6); HU (3); JP (15); PA (1); KR (6); AU (4); FR (7); IN (15); DE (4); BR (8); BU (4); PH (4); ME (1); IT (8); ES (11)