Clinical trial NCT06497504: Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Official title: A Multicenter, Randomized, Double-Blind, Placebo-controlled Study to Assess the Efficacy and Safety of Treatment With Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection on Antiretroviral Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hepatitis B
Keywords: Antiretroviral treatment
Bepirovirsen
Human immunodeficiency virus
Hepatitis B virus
Placebo
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-07-11
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of bepirovirsen compared to placebo in participants with human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection.


Eligibility criteria: Inclusion Criteria:

1. Documented chronic hepatitis B virus (HBV) infection and documented human immunodeficiency virus (HIV)-1 infection greater than equal to (\>=) 12 months prior to Screening.
2. Must be on uninterrupted antiretroviral therapy (ART) containing at least tenofovir disoproxil (TDF) or tenofovir alafenamide (TAF) plus lamivudine (3TC) or emtricitabine (FTC) for greater than (\>)12 months, with no planned changes to the stable regimen over the duration of the study.

   o Switch in ART is permitted \>=6 months prior to Screening for reasons not related to loss of HIV or HBV control (e.g., change in formulary, tolerability, side effects).
3. Documented evidence of at least 2 plasma HIV-1 ribonucleic acid (RNA) measurements less than (\<) 50 copies per milliliter (copies/mL) are required in the 12 months prior to Screening: 1 within 6 to 12 months prior to Screening and 1 within 6 months prior to Screening.
4. Plasma or serum HBV deoxyribonucleic acid (DNA) concentration must be adequately suppressed, defined as plasma or serum HBV DNA \<90 international units per milliliter (IU/mL).
5. Plasma or serum HBsAg concentration \>100 IU/mL and \<=3000 IU/mL.
6. Plasma HIV-1 RNA concentration must be undetectable, defined as plasma HIV 1 RNA \<50 copies/mL.
7. Cluster of differentiation 4 (CD4) count \>=350 cells per cubic millimeter (cells/mm\^3).
8. Alanine aminotransferase (ALT) \<=2 times upper limit of normal (ULN).

Exclusion Criteria:

1. History of or suspected liver cirrhosis and/or evidence of cirrhosis.
2. Diagnosed or suspected hepatocellular carcinoma (HCC).
3. History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension).
4. Coinfection with:

   1. Hepatitis C virus (HCV) with positive HCV antibody and detectable HCV RNA at Screening.

      I. HCV treatment should have completed \>12 months prior to Screening.
   2. Hepatitis D virus (HDV) defined as positive or equivocal HDV antibody regardless of HDV RNA level.
5. Clinically significant abnormalities, aside from HIV-1 infection and chronic HBV infection in medical history (e.g., moderate severe liver disease other than chronic HBV/HIV, acute coronary syndrome within 6 months of Screening, major surgery within 3 months of Screening, significant/unstable cardiac disease, uncontrolled diabetes, bleeding diathesis coagulopathy) or clinically significant physical examination findings.
6. Untreated syphilis infection (positive rapid plasma reagin \[RPR\] at Screening without clear documentation of treatment) are excluded unless they complete treatment during the Screening period and 7 days prior to randomization.
7. History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer). Participants under evaluation for possible malignancy are not eligible.
8. 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).
9. Participants who in the investigator's judgment, have a significant risk of suicide or self-harm.
10. Alcohol or drug abuse/dependence
11. 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.
12. Participants to whom immunosuppressive treatment, including therapeutic doses of steroids, is contraindicated should not be considered for enrolment in the study.
13. Currently taking, or has taken within 12 months of Screening, any interferon containing therapy.
14. Participants requiring anti coagulation therapies (e.g., warfarin, Factor Xa inhibitors) or anti platelet agents (including but not limited to clopidogrel or aspirin) unless treatment can safely be discontinued throughout duration of study intervention, by the discretion of the investigator. Occasional use is permitted.
15. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
16. Prior treatment with any oligonucleotide or small interfering ribonucleic acid (siRNA) within 12 months prior to the first dosing day.
17. Prior treatment with bepirovirsen.

Primary outcomes:
measure: Percentage of participants achieving hepatitis B virus (HBV) virologic response at 36 weeks after scheduled end of study treatment in absence of rescue medication
timeFrame: At study week 60
Secondary outcomes:
measure: Percentage of participants achieving HBV virologic response at the scheduled end of study treatment in absence of rescue medication
timeFrame: At study week 24
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Hillsborough
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Almagro
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: La Plata
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: Aracaju
country: Brazil
facility: GSK Investigational Site
city: Campinas
country: Brazil
facility: GSK Investigational Site
city: Curitiba
country: Brazil
facility: GSK Investigational Site
city: Salvador
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Marseille
country: France
facility: GSK Investigational Site
city: Melun
country: France
facility: GSK Investigational Site
city: Montpellier Cedex 5
country: France
facility: GSK Investigational Site
city: Nantes cedex 1
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Firenze
country: Italy
facility: GSK Investigational Site
city: Genova
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Sassari
country: Italy
facility: GSK Investigational Site
city: Durban
country: South Africa
facility: GSK Investigational Site
city: Johannesburg
country: South Africa
facility: GSK Investigational Site
city: Reiger Park
country: South Africa
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Cordoba
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: Madrid
country: Spain
facility: GSK Investigational Site
city: Banchiau Taipei
country: Taiwan
facility: GSK Investigational Site
city: Kaohsiung
country: Taiwan
facility: GSK Investigational Site
city: Bristol Avon
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: