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

• ClinicalTrials.gov Identifier: NCT05630807
• Recruitment Status: Recruiting
• First Posted: November 30, 2022
• Last Update Posted: July 10, 2023
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: November 21, 2022
• First Posted Date: November 30, 2022
• Last Update Posted Date: July 10, 2023
• Actual Study Start Date: December 7, 2022
• Estimated Primary Completion Date: October 15, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 7, 2023)

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.

Original Primary Outcome Measures (submitted: November 21, 2022)

Number of participants achieving functional cure (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) off all HBV treatment with HBsAg loss (<0.05 IU/mL) with or without HBsAb after a finite duration of therapy.

Current Secondary Outcome Measures (submitted: July 7, 2023)

• 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: November 21, 2022)

• Number of participants achieving 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 (<LLOQ) off all HBV treatment with HBsAg loss (<0.05 IU/mL) with or without HBsAb after a finite duration of therapy.
• 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.
• 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants With Chronic Hepatitis B (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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a multicenter, randomized, double-blind, placebo-controlled study.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

This will be a double blinded study in which investigators/site staff and the Sponsor will remain blinded to treatment assignment.

Primary Purpose: Treatment

• Condition: Chronic Hepatitis B

Intervention

• Drug: Bepirovirsen
  Bepirovirsen will be administered.
• Other: Placebo
  Matching placebo will be administered.

Study Arms

• Experimental: Bepirovirsen
  Intervention: Drug: Bepirovirsen
• Placebo Comparator: Placebo
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 7, 2023): 900
• Original Estimated Enrollment (submitted: November 21, 2022): 534
• Estimated Study Completion Date: April 1, 2026
• Estimated Primary Completion Date: October 15, 2025 (Final data collection date for primary outcome measure)

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) 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: US GSK Clinical Trials Call Center; 877-379-3718; GSKClinicalSupportHD@gsk.com

Contact: EU GSK Clinical Trials Call Center; +44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

• Listed Location Countries: Argentina, Canada, France, Italy, Japan, Korea, Republic of, Poland, Spain

Administrative Information

• NCT Number: NCT05630807
• Other Study ID Numbers: 202009; 2021-005139-22 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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/
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• 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.
• URL: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

• Current Responsible Party: GlaxoSmithKline
• Original Responsible Party: Same as current
• Current Study Sponsor: GlaxoSmithKline
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: July 2023