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

Chronic Hepatitis B Clinical Trial

— B-Well 1  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05630807
• Other study ID #: 202009
• Secondary ID: 2021-005139-22
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 7, 2022
• Est. completion date: May 8, 2026

Study information

• Verified date: May 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 941
• Est. completion date: May 8, 2026
• Est. primary completion date: November 24, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Bepirovirsen
Bepirovirsen will be administered.

Other:
• Placebo
Matching placebo will be administered.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Caba	Buenos Aires
Argentina	GSK Investigational Site	Caba	Buenos Aires
Argentina	GSK Investigational Site	CABA-Ciudad De Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Derqui, Pilar	Buenos Aires
Argentina	GSK Investigational Site	Rosario	Santa Fe
Brazil	GSK Investigational Site	Aracaju	Sergipe
Brazil	GSK Investigational Site	Campinas	São Paulo
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Manaus	Amazonas
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Santa Maria	Rio Grande Do Sul
Brazil	GSK Investigational Site	Sao Paulo	São Paulo
Brazil	GSK Investigational Site	Sao Paulo
Brazil	GSK Investigational Site	São Paulo
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Veliko Tarnovo
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Québec
Canada	GSK Investigational Site	St-Jerome	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Vancouver	British Columbia
Canada	GSK Investigational Site	Victoria	British Columbia
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Changchun	Jilin
China	GSK Investigational Site	Chengdu	Sichuan
China	GSK Investigational Site	Chongqing	Sichuan
China	GSK Investigational Site	Fuzhou
China	GSK Investigational Site	Guangzhou
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Hangzhou
China	GSK Investigational Site	Hangzhou
China	GSK Investigational Site	Kunming	Yunnan
China	GSK Investigational Site	Nanjing	Jiangsu
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shenyang	Liaoning
China	GSK Investigational Site	Shenzhen
China	GSK Investigational Site	Urumqi	Xinjiang
China	GSK Investigational Site	Wuhan	Hubei
China	GSK Investigational Site	Xi'an
China	GSK Investigational Site	Zhengzhou
China	GSK Investigational Site	Zhenjiang	Jiangsu
France	GSK Investigational Site	Clermont-Ferrand
France	GSK Investigational Site	Clichy Cedex
France	GSK Investigational Site	Dijon Cedex
France	GSK Investigational Site	Lille cedex
France	GSK Investigational Site	Pessac cedex
France	GSK Investigational Site	Poitiers
France	GSK Investigational Site	Rennes cedex 09
France	GSK Investigational Site	Strasbourg Cedex
France	GSK Investigational Site	Toulouse cedex
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Munchen	Bayern
Greece	GSK Investigational Site	Alexandroupolis
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Rio
Hong Kong	GSK Investigational Site	Lai King
Hong Kong	GSK Investigational Site	Pokfulam
Hong Kong	GSK Investigational Site	Shatin
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Eger
Hungary	GSK Investigational Site	Gyula
Hungary	GSK Investigational Site	Miskolc
India	GSK Investigational Site	Belagavi	Karnataka
India	GSK Investigational Site	Chandigarh
India	GSK Investigational Site	Chennai	Tamil Nadu
India	GSK Investigational Site	Coimbatore	Tamil Nadu
India	GSK Investigational Site	Guhawati	Assam
India	GSK Investigational Site	Hyderabad	Telangana
India	GSK Investigational Site	Hyderabad
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	Maharashtra
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Surat	Gujarat
Italy	GSK Investigational Site	Baggiovara (MO)	Emilia-Romagna
Italy	GSK Investigational Site	Brescia	Lombardia
Italy	GSK Investigational Site	Foggia	Puglia
Italy	GSK Investigational Site	Messina	Sicilia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Japan	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	Hyogo
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
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Daegu-si
Korea, Republic of	GSK Investigational Site	Daejeon
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Malaysia	GSK Investigational Site	Georgetown
Malaysia	GSK Investigational Site	Johor Bahru
Malaysia	GSK Investigational Site	Kota Bharu
Malaysia	GSK Investigational Site	Kota Kinabalu
Malaysia	GSK Investigational Site	Kuala Lumpur,
Malaysia	GSK Investigational Site	Kuantan	Pahang
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Oaxaca
Panama	GSK Investigational Site	Ciudad de Panama
Poland	GSK Investigational Site	Bytom
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Lancut
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Cluj Napoca
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Suceava
Romania	GSK Investigational Site	Timisoara
Singapore	GSK Investigational Site	Singapore
Singapore	GSK Investigational Site	Singapore
Spain	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	Pontevedra
Spain	GSK Investigational Site	Salamanca
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valladolid
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taoyuan
Thailand	GSK Investigational Site	Bangkok
Turkey	GSK Investigational Site	Ankara
United Kingdom	GSK Investigational Site	Birmingham
United Kingdom	GSK Investigational Site	Edinburgh
United Kingdom	GSK Investigational Site	Leeds
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Chandler	Arizona
United States	GSK Investigational Site	Homestead	Florida
United States	GSK Investigational Site	Iowa City	Iowa
United States	GSK Investigational Site	Littleton	Colorado
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Novi	Michigan
United States	GSK Investigational Site	Palo Alto	California
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	San Jose	California
United States	GSK Investigational Site	Tucson	Arizona
Vietnam	GSK Investigational Site	Hanoi
Vietnam	GSK Investigational Site	Ho Chi Minh City

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Brazil,  Bulgaria,  Canada,  China,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Panama,  Poland,  Romania,  Singapore,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 (	Up to 72 weeks
Secondary	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
Secondary	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