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

July 7, 2023 updated by: GlaxoSmithKline

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

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

900

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Argentina
    • Buenos Aires
      • Caba, Buenos Aires, Argentina, C1061AAS
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Fernando Mario Gruz
  • Canada
    • British Columbia
      • Victoria, British Columbia, Canada, V8R 6R3
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Wayne Ghesquiere
  • France
      • Clichy Cedex, France, 92118
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Tarik Asselah
        • Contact:
        • Contact:
  • Italy
    • Lombardia
      • Milano, Lombardia, Italy, 20122
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Pietro Lampertico
        • Contact:
        • Contact:
  • Japan
      • Hokkaido, Japan, 053-8506
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Shinya Minami
        • Contact:
        • Contact:
      • Kumamoto, Japan, 862-8655
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Shigetoshi Fujiyama
        • Contact:
        • Contact:
  • Korea, Republic of
      • Daegu, Korea, Republic of, 700-721
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • YoungOh Kweon
        • Contact:
        • Contact:
      • Seoul, Korea, Republic of, 08308
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Ji Hoon Kim
        • Contact:
        • Contact:
      • Seoul, Korea, Republic of, 07061
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Won Kim
        • Contact:
        • Contact:
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Yoon Jun Kim
        • Contact:
        • Contact:
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Geum-Youn Gwak
        • Contact:
        • Contact:
  • Poland
      • Bytom, Poland, 41-902
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Jerzy Jaroszewicz
        • Contact:
        • Contact:
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Maria Buti
        • Contact:
        • Contact:
      • Barcelona, Spain, 08036
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Sabela Lens García
        • Contact:
        • Contact:
      • Madrid, Spain, 28041
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Inmaculada Fernández Vázquez
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Time Frame: Up to 72 weeks
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
Time Frame: Up to 72 weeks
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
Time Frame: Up to 72 weeks
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
Time Frame: Up to 72 weeks
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

This is where you will find people and organizations involved with this study.

Sponsor

GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 7, 2022

Primary Completion (Estimated)

October 15, 2025

Study Completion (Estimated)

April 1, 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)

July 10, 2023

Last Update Submitted That Met QC Criteria

July 7, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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