A Study in Chronic Hepatitis B e-Antigen Negative Participants After Discontinuation of Nucleos(t)Ide Analog (NA) Treatment

NCT ID: NCT05550519

Last Updated: 2025-06-25

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: EARLY_PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-31
• Study Completion Date: 2025-08-28

Brief Summary

The purpose of this study is to assess the incidence of participants who reach hepatitis B surface antigen (HBsAg) seroclearance after discontinuing nucleos(t)ide analog (NA) therapy in participants with HBsAg less than or equal to (<=) 100 international units per milliliter (IU/mL) and participants with HBsAg greater than (>) 100 IU/mL to <= 500 IU/mL at baseline.

Detailed Description

Hepatitis B virus (HBV) virus infects the human liver. It consists of a nucleocapsid with hepatitis B core (HBc) protein and a membranous envelope containing hepatitis B surface antigen (HBsAg). Chronic hepatitis B (CHB) virus infection may lead to liver cirrhosis and hepatocellular carcinoma (HCC). Recent guidelines (European Association for the Study of the Liver [EASL] guidelines, Asian Pacific Association for the Study of the Liver [APASL] guidelines) suggest that discontinuation of treatment with nucleos(t)ide analog (NA) (Entecavir [ETV], tenofovir disoproxil fumarate [TDF] or tenofovir alafenamide [TAF]) in non-cirrhotic Hepatitis B e antigen (HBeAg) negative patients after a minimum of three years of viral suppression can trigger changes in virological and immune composition resulting in achieving HBsAg seroclearance (up to 25 percent [%]). The study will be conducted in 3 phases: screening phase (up to 6 weeks), baseline visit (1 day), and post-NA discontinuation phase (up to 96 weeks) which refers to the phase after baseline, in which treatment will be discontinued (off treatment). Discontinuation of NA treatment is considered as study intervention in this study. Collection of core liver biopsy, fine needle aspiration (FNA), and blood samples are considered study investigations/procedures. The participants will be followed for up to 2 years post-NA treatment discontinuation. The total duration of an individual participation will be up to 102 weeks (including up to 6 weeks for screening and baseline).

Conditions

Hepatitis B, Chronic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Discontinuation of Nucleos(t)ide (NA) Treatment

Participants will receive standard of care NA treatment (Entecavir \[ETV\], Tenofovir Disoproxil Fumarate \[TDF\], Tenofovir Alafenamide \[TAF\]) in screening phase (up to 6 weeks) and in baseline visit (Day -1). NA treatment will be discontinued on Day 1 up to 96 weeks (Post-NA discontinuation off-treatment phase). Off-treatment refers to the phase after baseline, in which NA treatment will be discontinued.

Group Type: EXPERIMENTAL

Entecavir (ETV)

Intervention Type: OTHER

ETV will continue throughout screening and will be stopped at baseline.

Tenofovir Disoproxil Fumarate (TDF)

Intervention Type: OTHER

TDF will continue throughout screening and will be stopped at baseline.

Tenofovir Alafenamide (TAF)

Intervention Type: OTHER

TAF will continue throughout screening and will be stopped at baseline.

Interventions

Entecavir (ETV)

ETV will continue throughout screening and will be stopped at baseline.

Intervention Type: OTHER

Tenofovir Disoproxil Fumarate (TDF)

TDF will continue throughout screening and will be stopped at baseline.

Intervention Type: OTHER

Tenofovir Alafenamide (TAF)

TAF will continue throughout screening and will be stopped at baseline.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Medically stable on the basis of physical examination, medical history, vital signs, and clinical laboratory tests performed at screening and during the pre-biopsy assessments. If the results of the serum chemistry panel including liver enzymes, blood coagulation, other specific tests, or hematology are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study (in consultation with sponsor)
• Hepatitis B surface antigen (HBsAg) less than or equal to (<=) 500 International units per milliliters (IU/mL) (and greater than [>] 5 IU/mL) at screening
• Hepatitis B e antigen (HBeAg) less than (<) lower limit of quantification and hepatitis B e antibody (HBeAb) positive at screening
• Normal liver ultrasound (at screening or within 3 months before screening [documented evidence])
• Participants must have a body mass index between 18.0 and 35.0 Kilograms per meter square (kg/m^2), extremes included

Exclusion Criteria

• History of or signs of cirrhosis or portal hypertension (absence of nodules, no smooth liver contour, no normal portal vein, spleen size greater than or equal to [>=] 12 centimeters [cm]) or signs of hepatocellular carcinoma (HCC) or clinically relevant renal abnormalities on an abdominal ultrasound performed within 3 months prior to screening (based on documented evidence, if available) or at the time of screening. In case of suspicious findings on conventional ultrasound the participant may still be eligible if HCC or clinically relevant renal abnormalities have been ruled out by a more specific imaging procedure (contrast enhanced ultrasound, computed tomography [CT] or magnetic resonance imaging [MRI])
• Participant's refusal to accept blood transfusions
• Participants with clinically relevant drug or alcohol abuse within 12 months before screening
• Received an investigational intervention or used an invasive investigational medical device within 3 months before the planned enrollment or is currently enrolled in an investigational study
• Participants of Asian descent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Pharmaceutica N.V., Belgium

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Pharmaceutica N.V., Belgium Clinical Trial

Role: STUDY_DIRECTOR

Janssen Pharmaceutica N.V., Belgium

Other Identifiers

NOPRODHPB0017

Identifier Type: OTHER

Identifier Source: secondary_id

2021-005588-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR109229

Identifier Type: -

Identifier Source: org_study_id