Clinical trial NCT05630820: Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants With Chronic Hepatitis B (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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2022-11-30
Enrollment: 871
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multicenter, randomized, double-blind, placebo-controlled study.
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of participants achieving functional cure (FC) with baseline HBsAg ≤3000 IU/mL
timeFrame: Up to 72 weeks
Secondary outcomes:
measure: Number of participants achieving FC with baseline HBsAg ≤1000 IU/mL
timeFrame: Up to 72 weeks
measure: Number of participants achieving sustained suppression of HBV DNA (<LLOQ) with baseline HBsAg ≤3000 IU/mL
timeFrame: Up to 72 weeks
measure: Number of participants achieving sustained suppression of HBV DNA (<LLOQ) with baseline HBsAg ≤1000 IU/mL
timeFrame: Up to 72 weeks
Other outcomes:
Locations:
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country: United States
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state: California
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state: California
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state: California
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state: Colorado
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city: Buenos Aires
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country: Argentina
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city: Santa Fe
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city: Box Hill
country: Australia
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city: Fitzroy
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city: Herston
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city: Westmead
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city: Botucatu
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country: Bulgaria
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city: Sliven
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Varna
country: Bulgaria
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city: Calgary
country: Canada
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city: Edmonton
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city: Edmonton
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city: Montreal
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city: Montreal
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city: Regina
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city: Beijing
country: China
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city: Beijing
country: China
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country: China
facility: GSK Investigational Site
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city: Shanghai
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facility: GSK Investigational Site
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city: Zhengzhou
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country: France
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city: Grenoble cedex 9
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city: Limoges cedex
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city: Lyon
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facility: GSK Investigational Site
city: Rouen cedex
country: France
facility: GSK Investigational Site
city: Toulouse cedex 9
country: France
facility: GSK Investigational Site
city: Frankfurt
country: Germany
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city: Frankfurt
country: Germany
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city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hannover
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Heraklion Crete
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Szeged
country: Hungary
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facility: GSK Investigational Site
city: Nagpur
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facility: GSK Investigational Site
city: New Delhi
country: India
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city: New Delhi
country: India
facility: GSK Investigational Site
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facility: GSK Investigational Site
city: Pune
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facility: GSK Investigational Site
city: Raipur
country: India
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city: Secunderabad
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facility: GSK Investigational Site
city: Milano
country: Italy
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city: Napoli
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city: Palermo
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city: Pisa
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city: Sassari
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city: Torino
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city: Hokkaido
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city: Hokkaido
country: Japan
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city: Hokkaido
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city: Ishikawa
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city: Kagawa
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city: Kumamoto
country: Japan
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city: Niigata
country: Japan
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city: Osaka
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country: Korea, Republic of
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city: Johor Bahru
country: Malaysia
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country: Malaysia
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country: Malaysia
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city: Kuantan
country: Malaysia
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country: Mexico
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country: New Zealand
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country: Panama
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country: Philippines
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country: Philippines
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country: Philippines
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country: Poland
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city: Myslowice
country: Poland
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city: Zychlin
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city: Bucharest
country: Romania
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city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Cluj Napoca
country: Romania
facility: GSK Investigational Site
city: Constanta
country: Romania
facility: GSK Investigational Site
city: Galati
country: Romania
facility: GSK Investigational Site
city: Oradea
country: Romania
facility: GSK Investigational Site
city: Alcorcon Madrid
country: Spain
facility: GSK Investigational Site
city: Badajoz
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Sabadell Barcelona
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valladolid
country: Spain
facility: GSK Investigational Site
city: Zaragoza
country: Spain
facility: GSK Investigational Site
city: Kaohsiung
country: Taiwan
facility: GSK Investigational Site
city: Taichung
country: Taiwan
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city: Tainan
country: Taiwan
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country: Taiwan
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country: Thailand
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city: Ankara
country: Turkey
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city: Istanbul
country: Turkey
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city: Izmir
country: Turkey
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city: Liverpool
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Middlesbrough
country: United Kingdom
facility: GSK Investigational Site
city: Newcastle upon Tyne
country: United Kingdom
facility: GSK Investigational Site
city: Plymouth
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: