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

Chronic Hepatitis B Clinical Trial

— B-Well 2  

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 2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05630820
• Other study ID #: 219288
• Secondary ID: 2022-002268-53
• Status: Recruiting
• Phase: Phase 3
• Start date: December 6, 2022
• Est. completion date: June 24, 2026

Study information

• Verified date: February 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• 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: Recruiting
• Enrollment: 900
• Est. completion date: June 24, 2026
• Est. primary completion date: January 7, 2026
• 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) 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	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Cordoba	Córdova
Argentina	GSK Investigational Site	Rio Cuarto
Argentina	GSK Investigational Site	Santa Fe
Argentina	GSK Investigational Site	Villa Regina	Río Negro
Australia	GSK Investigational Site	Box Hill	Victoria
Australia	GSK Investigational Site	Fitzroy	Victoria
Australia	GSK Investigational Site	Herston	Queensland
Australia	GSK Investigational Site	Westmead	New South Wales
Brazil	GSK Investigational Site	Alto Da Posse, Nova Iguacu
Brazil	GSK Investigational Site	Botucatu	São Paulo
Brazil	GSK Investigational Site	Fortaleza	Ceará
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Rio de Janeiro
Brazil	GSK Investigational Site	Salvador	Bahia
Brazil	GSK Investigational Site	Vitoria	Espirito Santo
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Sliven
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Varna
Canada	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	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Regina	Saskatchewan
Canada	GSK Investigational Site	Toronto	Ontario
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	Guangzhou	Guangdong
China	GSK Investigational Site	Guangzhou
China	GSK Investigational Site	Hangzhou
China	GSK Investigational Site	Hangzhou
China	GSK Investigational Site	Hefei	Anhui
China	GSK Investigational Site	Kunming	Yunnan
China	GSK Investigational Site	Liuzhou
China	GSK Investigational Site	Nanjing	Jiangsu
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	Urumqi	Xinjiang
China	GSK Investigational Site	Wuhan	Hubei
China	GSK Investigational Site	Xi'an
China	GSK Investigational Site	Xiamen
China	GSK Investigational Site	Zhengzhou
China	GSK Investigational Site	Zunyi
France	GSK Investigational Site	Créteil cedex
France	GSK Investigational Site	Créteil Cedex
France	GSK Investigational Site	Grenoble cedex 9
France	GSK Investigational Site	Limoges cedex
France	GSK Investigational Site	Lyon cedex 04
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Paris Cedex 13
France	GSK Investigational Site	Rouen cedex
France	GSK Investigational Site	Toulouse cedex 9
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt am Main	Hessen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Heraklion
Greece	GSK Investigational Site	Kifisia
Greece	GSK Investigational Site	Thessaloniki
Hungary	GSK Investigational Site	Szeged
Hungary	GSK Investigational Site	Székesfehérvár
Hungary	GSK Investigational Site	Zalaegerszeg
India	GSK Investigational Site	Ahmedabad	Gujarat
India	GSK Investigational Site	Chennai
India	GSK Investigational Site	Haryana
India	GSK Investigational Site	Kanpur
India	GSK Investigational Site	Kochi
India	GSK Investigational Site	Kolkata
India	GSK Investigational Site	Kolkata	West Bengal
India	GSK Investigational Site	Mumbai	Maharashtra
India	GSK Investigational Site	Mumbai	Maharashtra
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	Chhattisgarh
India	GSK Investigational Site	Secunderabad
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Napoli	Campania
Italy	GSK Investigational Site	Padova	Veneto
Italy	GSK Investigational Site	Palermo	Sicilia
Italy	GSK Investigational Site	Pisa	Toscana
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Sassari	Sardegna
Italy	GSK Investigational Site	Torino	Piemonte
Japan	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
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Ulsan
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	Kuala Terengganu
Malaysia	GSK Investigational Site	Kuantan
Mexico	GSK Investigational Site	Aguascalientes
Mexico	GSK Investigational Site	Aguascalientes
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Tlalnepantla
New Zealand	GSK Investigational Site	Auckland
New Zealand	GSK Investigational Site	Papatoetoe, Auckland
Panama	GSK Investigational Site	Panama
Philippines	GSK Investigational Site	Cebu City
Philippines	GSK Investigational Site	Makati City
Philippines	GSK Investigational Site	Pasig
Philippines	GSK Investigational Site	Silang	Cavite
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Myslowice
Poland	GSK Investigational Site	Zychlin
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Cluj-Napoca
Romania	GSK Investigational Site	Constanta
Romania	GSK Investigational Site	Galati
Romania	GSK Investigational Site	Oradea
Singapore	GSK Investigational Site	Singapore
Spain	GSK Investigational Site	Alcorcon	Madrid
Spain	GSK Investigational Site	Almería
Spain	GSK Investigational Site	Badajoz
Spain	GSK Investigational Site	Caceres / Caceres	Caceres / Extremadura
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	Sevilla
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valladolid
Spain	GSK Investigational Site	Zaragoza
Spain	GSK Investigational Site	Zaragoza
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Tainan
Taiwan	GSK Investigational Site	Taipei
Thailand	GSK Investigational Site	Chiangmai
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Istanbul
Turkey	GSK Investigational Site	Izmir
United Kingdom	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	Plymouth
United States	GSK Investigational Site	Centreville	Alabama
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Denison	Texas
United States	GSK Investigational Site	Fort Pierce	Florida
United States	GSK Investigational Site	Glen Burnie	Maryland
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Seattle	Washington
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,  Australia,  Brazil,  Bulgaria,  Canada,  China,  France,  Germany,  Greece,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  New Zealand,  Panama,  Philippines,  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	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