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

Phase 3 Multicenter, Randomized, Double-Blind, Study to Assess the Efficacy and Safety of Treatment With Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants With Chronic Hepatitis B Virus (B-Well 1)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B; Hepatitis B, Chronic
• Intervention / Treatment: Drug: Bepirovirsen; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 981
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1061AAS
    • GSK Investigational Site
  • Buenos Aires, Argentina, 1061
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1125ABE
    • GSK Investigational Site
  • Capital Federal, Argentina, C1181ACI
    • GSK Investigational Site
  • Pilar, Argentina, B1629AHJ
    • GSK Investigational Site
  • Rosario, Argentina, S2002KDT
    • GSK Investigational Site
• Brazil
  • Aracaju, Brazil, 49060-010
    • GSK Investigational Site
  • Campinas, Brazil, 13034-685
    • GSK Investigational Site
  • Curitiba, Brazil, 80810-050
    • GSK Investigational Site
  • Manaus, Brazil, 69040-000
    • GSK Investigational Site
  • Porto Alegre, Brazil, 90035003
    • GSK Investigational Site
  • Santa Maria, Brazil, 97105-900
    • GSK Investigational Site
  • São Paulo, Brazil, 08270-070
    • GSK Investigational Site
  • São Paulo, Brazil, 05403-000
    • GSK Investigational Site
  • Vila Mariana, Brazil, 04121-000
    • GSK Investigational Site
• Bulgaria
  • Sofia, Bulgaria, 1431
    • GSK Investigational Site
  • Sofia, Bulgaria, 1606
    • GSK Investigational Site
  • Sofia, Bulgaria
    • GSK Investigational Site
  • Veliko Tarnovo, Bulgaria, 5000
    • GSK Investigational Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • GSK Investigational Site
    • Victoria, British Columbia, Canada, V8V 3M9
      • GSK Investigational Site
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5G 2C4
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H2X 0A9
      • GSK Investigational Site
    • Québec, Quebec, Canada, G1V 4G2
      • GSK Investigational Site
    • Saint-Jérôme, Quebec, Canada, J7Z 2V4
      • GSK Investigational Site
• China
  • Beijing, China
    • GSK Investigational Site
  • Beijing, China, 100050
    • GSK Investigational Site
  • Beijing, China, 100015
    • GSK Investigational Site
  • Changchun, China, 130021
    • GSK Investigational Site
  • Chengdu, China
    • GSK Investigational Site
  • Chongqing, China, 400042
    • GSK Investigational Site
  • Fuzhou, China, 350025
    • GSK Investigational Site
  • Guangzhou, China, 510630
    • GSK Investigational Site
  • Guangzhou, China, 510060
    • GSK Investigational Site
  • Guangzhou, China, 510515
    • GSK Investigational Site
  • Hangzhou, China, 310003
    • GSK Investigational Site
  • Hangzhou, China, 310022
    • GSK Investigational Site
  • Kunming, China, 650021
    • GSK Investigational Site
  • Nanjing, China, 210008
    • GSK Investigational Site
  • Shanghai, China, 200025
    • GSK Investigational Site
  • Shanghai, China, 200040
    • GSK Investigational Site
  • Shanghai, China, 200083
    • GSK Investigational Site
  • Shenyang, China, 110022
    • GSK Investigational Site
  • Shenzhen, China, 518112
    • GSK Investigational Site
  • Wuhan, China, 430022
    • GSK Investigational Site
  • Xi'an, China, 710061
    • GSK Investigational Site
  • Zhengzhou, China, 450000
    • GSK Investigational Site
  • Zhenjiang, China
    • GSK Investigational Site
  • Ürümqi, China, 830054
    • GSK Investigational Site
• France
  • Clermont-Ferrand, France, 63003
    • GSK Investigational Site
  • Clichy, France, 92118
    • GSK Investigational Site
  • Dijon, France, 21079
    • GSK Investigational Site
  • Lille, France, 59037
    • GSK Investigational Site
  • Pessac, France, 33604
    • GSK Investigational Site
  • Poitiers, France, 86021
    • GSK Investigational Site
  • Rennes, France, 35033
    • GSK Investigational Site
  • Strasbourg, France, 67091
    • GSK Investigational Site
  • Toulouse, France, 31059
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10787
    • GSK Investigational Site
  • Berlin, Germany, 10439
    • GSK Investigational Site
  • Berlin, Germany, 12163
    • GSK Investigational Site
  • Berlin, Germany, 10243
    • GSK Investigational Site
  • Bochum, Germany, 44787
    • GSK Investigational Site
  • Cologne, Germany, 50668
    • GSK Investigational Site
  • Düsseldorf, Germany, 40225
    • GSK Investigational Site
  • München, Germany, 80336
    • GSK Investigational Site
• Greece
  • Athens, Greece, 10676
    • GSK Investigational Site
  • Athens, Greece, 11527
    • GSK Investigational Site
  • Periohi Dragana Alexand, Greece, 68100
    • GSK Investigational Site
  • Rio Patras, Greece, 26504
    • GSK Investigational Site
• Hong Kong
  • Kowloon, Hong Kong
    • GSK Investigational Site
  • Pokfulam, Hong Kong
    • GSK Investigational Site
  • Shatin, Hong Kong
    • GSK Investigational Site
• Hungary
  • Budapest, Hungary, 1097
    • GSK Investigational Site
  • Eger, Hungary, 3300
    • GSK Investigational Site
  • Gyula, Hungary, 5700
    • GSK Investigational Site
  • Miskolc, Hungary, 3530
    • GSK Investigational Site
• India
  • Belagavi, India, 590010
    • GSK Investigational Site
  • Chandigarh, India, 160012
    • GSK Investigational Site
  • Chennai, India, 600113
    • GSK Investigational Site
  • Coimbatore, India, 641005
    • GSK Investigational Site
  • Guhawati, India, 781006
    • GSK Investigational Site
  • Hyderabad, India, 500033
    • GSK Investigational Site
  • HyderabadTelangana, India, 500048
    • GSK Investigational Site
  • Jaipur, India, 302001
    • GSK Investigational Site
  • Ludhiana, India, 141001
    • GSK Investigational Site
  • Manipal, India, 576104
    • GSK Investigational Site
  • Mumbai, India, 400 008
    • GSK Investigational Site
  • Mumbai, India, 400012
    • GSK Investigational Site
  • Mumbai, India, 400026
    • GSK Investigational Site
  • Pune, India, 411001
    • GSK Investigational Site
  • Surat, India, 395002
    • GSK Investigational Site
• Italy
  • Brescia, Italy, 25123
    • GSK Investigational Site
  • Foggia, Italy, 71100
    • GSK Investigational Site
  • Messina, Italy, 98124
    • GSK Investigational Site
  • Milan, Italy, 20122
    • GSK Investigational Site
  • Milan, Italy, 20162
    • GSK Investigational Site
  • Modena, Italy, 40126
    • GSK Investigational Site
• Japan
  • Chiba, Japan, 272-8516
    • GSK Investigational Site
  • Ehime, Japan, 790-8524
    • GSK Investigational Site
  • Fukuoka, Japan, 820-8505
    • GSK Investigational Site
  • Fukuoka, Japan, 839-0863
    • GSK Investigational Site
  • Gifu, Japan, 500-8717
    • GSK Investigational Site
  • Gifu, Japan, 503-8502
    • GSK Investigational Site
  • Hiroshima, Japan, 737-0023
    • GSK Investigational Site
  • Hiroshima, Japan, 734-8551
    • GSK Investigational Site
  • Hokkaido, Japan, 053-8506
    • GSK Investigational Site
  • Hyōgo, Japan, 660-8550
    • GSK Investigational Site
  • Kumamoto, Japan, 862-8655
    • GSK Investigational Site
  • Miyagi, Japan, 980-8574
    • GSK Investigational Site
  • Tokyo, Japan, 180-8610
    • GSK Investigational Site
  • Tokyo, Japan, 113-8519
    • GSK Investigational Site
  • Tokyo, Japan, 173-8610
    • GSK Investigational Site
• Malaysia
  • George Town, Malaysia
    • GSK Investigational Site
  • Johor Bahru, Malaysia, 80100
    • 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
• Mexico
  • Guadalajara, Mexico, 44160
    • GSK Investigational Site
  • Oaxaca City, Mexico, 68000
    • GSK Investigational Site
• Panama
  • Panama City, Panama, 07206
    • GSK Investigational Site
• Poland
  • Bytom, Poland, 41-902
    • GSK Investigational Site
  • Krakow, Poland, 31-202
    • GSK Investigational Site
  • Łańcut, Poland, 37-100
    • GSK Investigational Site
• Romania
  • Bucharest, Romania, 021105
    • GSK Investigational Site
  • Bucharest, Romania, 20125
    • GSK Investigational Site
  • Cluj-Napoca, Romania, 400162
    • GSK Investigational Site
  • Iași, Romania, 700116
    • GSK Investigational Site
  • Suceava, Romania, 720224
    • GSK Investigational Site
  • Timișoara, Romania, 300001
    • GSK Investigational Site
• Singapore
  • Singapore, Singapore, 119074
    • GSK Investigational Site
  • Singapore, Singapore, 169608
    • GSK Investigational Site
• South Korea
  • Ansan, South Korea, 15355
    • GSK Investigational Site
  • Busan, South Korea, 47392
    • GSK Investigational Site
  • Daegu, South Korea, 42601
    • GSK Investigational Site
  • Daegu, South Korea, 41944
    • GSK Investigational Site
  • Seoul, South Korea, 03080
    • GSK Investigational Site
  • Seoul, South Korea, 06351
    • GSK Investigational Site
  • Seoul, South Korea, 08308
    • GSK Investigational Site
  • Seoul, South Korea, 07061
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08036
    • GSK Investigational Site
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • León, Spain, 24080
    • GSK Investigational Site
  • Madrid, Spain, 28041
    • GSK Investigational Site
  • Málaga, Spain, 29010
    • GSK Investigational Site
  • Salamanca, Spain, 37007
    • GSK Investigational Site
  • Santander, Spain, 39008
    • GSK Investigational Site
  • Valencia, Spain, 46014
    • GSK Investigational Site
  • Valladolid, Spain, 47003
    • GSK Investigational Site
  • Vigo, Spain, 36002
    • GSK Investigational Site
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • GSK Investigational Site
  • Kaohsiung City, Taiwan, 833
    • GSK Investigational Site
  • Taichung, Taiwan, 40705
    • GSK Investigational Site
  • Taipei, Taiwan, 104
    • GSK Investigational Site
  • Tau-Yuan, Taiwan, 333
    • GSK Investigational Site
• Thailand
  • Bangkok, Thailand, 10330
    • GSK Investigational Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • GSK Investigational Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • GSK Investigational Site
  • Edinburgh, United Kingdom, EH4 2XU
    • GSK Investigational Site
  • Leeds West Yorkshire, United Kingdom, LS9 7TF
    • GSK Investigational Site
  • London, United Kingdom, SE5 9RS
    • GSK Investigational Site
  • London, United Kingdom, SW17 0QT
    • GSK Investigational Site
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • GSK Investigational Site
  • California
    • Davis, California, United States, 95817
      • GSK Investigational Site
    • Los Angeles, California, United States, 90027
      • GSK Investigational Site
    • Palo Alto, California, United States, 94304
      • GSK Investigational Site
    • San Jose, California, United States, 95116
      • GSK Investigational Site
  • Colorado
    • Littleton, Colorado, United States, 80120
      • GSK Investigational Site
  • Florida
    • Miami, Florida, United States, 33134
      • GSK Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • GSK Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • GSK Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48377
      • GSK Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23249
      • GSK Investigational Site
    • Richmond, Virginia, United States, 23298
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Matching placebo will be administered.
Experimental: Bepirovirsen	Drug: Bepirovirsen; Bepirovirsen will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants achieving sustained suppression of HBV DNA (<LLOQ) with baseline HBsAg ≤3000 IU/mL	The number of participants who achieved sustained suppression of HBV DNA after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication will be reported.	Up to 72 weeks
Number of participants achieving sustained suppression of HBV DNA (<LLOQ) with baseline HBsAg ≤1000 IU/mL	The number of participants who achieved sustained suppression of HBV DNA after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication will be reported.	Up to 72 weeks
Number of participants achieving FC with baseline HBsAg ≤1000 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 (<LLOQ) and HBsAg not detected with or without HBsAb after a finite duration of therapy.	Up to 72 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2022
• Primary Completion (Actual): November 11, 2025
• Study Completion (Actual): April 15, 2026

Study Registration Dates

• First Submitted: November 21, 2022
• First Submitted That Met QC Criteria: November 21, 2022
• First Posted (Actual): November 30, 2022

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Hepatitis; Chronic Hepatitis; Nucleos(t)ide analogue; Chronic Hepatitis B; Hepatitis B Virus; hepatitis B virus e-antigen; Bepirovirsen; Antisense Oligonucleotide; 202009; 219288
• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Pathological Conditions, Signs and Symptoms; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: 202009; 2021-005139-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No