Phase 3 Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants With Chronic Hepatitis B (B-Well 2)

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05630820

Collaborator

(none)

534

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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:

Double-blind treatment (bepirovirsen or placebo) for 24 weeks;
Nucleos(t)ide analogue (NA) treatment for 24 weeks;
NA cessation with 24 week follow up OR
Continue NA for 24 weeks, 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 units per milliliter [IU/mL] to ≤1000 IU/mL or >1000 IU/mL to less than or equal to [≤] 3000 IU/mL) at screening.

The total duration of the study, including screening (up to 45 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 102 weeks for each participant.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: Bepirovirsen Other: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

534 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a multicenter, randomized, double-blind, placebo-controlled study.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 blinding study in which investigators/site staff and the Sponsor will remain blinded to treatment assignment.

Primary Purpose:

Treatment

Official Title:

Phase 3 Multicenter, Randomized, Double Blind, Study to Assess the Efficacy and Safety of Treatment With Bepirovirsen in HBeAg Negative Nucleos(t)Ide Analogue Treated Participants With Chronic Hepatitis B Virus (B Well 2)

Anticipated Study Start Date :

Nov 30, 2022

Anticipated Primary Completion Date :

Oct 15, 2025

Anticipated Study Completion Date :

Apr 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bepirovirsen	Drug: Bepirovirsen Bepirovirsen will be administered.
Placebo Comparator: Placebo	Other: Placebo Matching placebo will be administered.

Arm

Intervention/Treatment

Experimental: Bepirovirsen

Drug: Bepirovirsen

Bepirovirsen will be administered.

Placebo Comparator: Placebo

Other: Placebo

Matching placebo will be administered.

Outcome Measures

Primary Outcome Measures

Number of participants achieving functional cure (FC) with baseline HBsAg ≤1000 IU/mL [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) with HBsAg loss (<0.05 IU/mL) with or without HBsAb after a finite duration of therapy.

Secondary Outcome Measures

Number of participants achieving FC with baseline HBsAg ≤3000 IU/mL [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) 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 [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants must be HBeAg negative at screening.
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).

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.