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

A Prospective Study to Investigate the Relationship Between Hepatitis B Surface Antigen (HBsAg) Loss and the Dynamics in Host and Viral Markers After Discontinuation of Nucleos(t)Ide Analog (NA) Treatment in Chronic Hepatitis B E-antigen Negative Patients With Low On-treatment HBsAg Level

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.

Study Overview

• Status: Withdrawn
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Other: Entecavir (ETV); Other: Tenofovir Disoproxil Fumarate (TDF); Other: Tenofovir Alafenamide (TAF)

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).

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Kolding, Denmark, 6000
    • Sygehus Lillebælt - Kolding Sygehus
  • Odense, Denmark, 5000
    • Odense Universitets Hospital
  • Roskilde, Denmark, 4000
    • Sjællands University hospital
• France
  • Bobigny, France, 93000
    • Hôpital Avicenne
  • La Tronche, France, 38700
    • CHU Grenoble
  • Lyon, France, 69317
    • Hôpital de la Croix Rousse
  • Rennes cedex 9, France, 35033
    • Hopital Pontchaillou
• Germany
  • Frankfurt, Germany, 60590
    • Universitatsklinikum Frankfurt
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Leipzig, Germany, 04109
    • Universitätsklinikum Leipzig
  • Leipzig, Germany, 04129
    • Klinikum Sankt Georg Neurologie
  • Tübingen, Germany, 72074
    • Eberhard Karls Universität Tübingen
• Greece
  • Athens, Greece, 11527
    • Laiko General Hospital of Athens
  • Athens, Greece, 10676
    • G.H. of Athens Evangelismos
  • Thessaloniki, Greece, 546 42
    • General Hospital of Thessaloniki Ippokrateio
• Italy
  • Brescia, Italy, 25123
    • ASST Spedali Civili di Brescia
  • Foggia, Italy, 71100
    • Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Modena, Italy, 41124
    • Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana
  • San Giovanni Rotondo, Italy, 71013
    • Casa Sollievo della Sofferenza
  • Torino, Italy, 10126
    • Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino
• Portugal
  • Braga, Portugal, 4835-044
    • Hosp. Sra. Da Oliveira - Guimaraes
  • Coimbra, Portugal, 3000075
    • Centro Hospitalar e Universitario de Coimbra
  • Lisboa, Portugal, 1649-035
    • Centro Hospitalar de Lisboa Norte - Hospital Santa Maria
  • Vila Real, Portugal, 5000-508
    • Centro Hospitalar de Trás os Montes e Alto Douro- Vila Real
• Spain
  • Barcelona, Spain, 08036
    • Hosp. Clinic I Provincial de Barcelona
  • Barcelona, Spain, 08003
    • Hosp. Del Mar
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
  • València, Spain, 46014
    • Hosp. Clinico Univ. de Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Other: Entecavir (ETV); ETV will continue throughout screening and will be stopped at baseline.; Other: Tenofovir Disoproxil Fumarate (TDF); TDF will continue throughout screening and will be stopped at baseline.; Other: Tenofovir Alafenamide (TAF); TAF will continue throughout screening and will be stopped at baseline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance After Discontinuation of Nucleos(t)ide Analog (NA) Treatment	Percentage of participants with HBsAg seroclearance after discontinuation of NA treatment will be reported.	At Week 24
Percentage of Participants with HBsAg Seroclearance After Discontinuation of NA Treatment	Percentage of participants with HBsAg seroclearance after discontinuation of NA treatment will be reported.	At Week 48
Percentage of Participants with HBsAg Seroclearance After Discontinuation of NA Treatment	Percentage of participants with HBsAg seroclearance after discontinuation of NA treatment will be reported.	At Week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Flares	Percentage of participants with flares (virologic, biochemical, and clinical) measured by blood markers (such as HBsAg, hepatitis B virus deoxyribonucleic acid [HBV DNA], and alanine aminotransferase [ALT]) will be reported.	At Week 24, Week 48, and Week 96
Change from Baseline Over Time in HBsAg Level	Change from baseline over time in HBsAg level will be reported.	Baseline up to 96 weeks
Change from Baseline Over Time in HBV DNA level	Change from baseline over time in HBV DNA level will be reported.	Baseline up to 96 weeks
Time to Achieve First HBsAg Seroclearance	Time to achieve first HBsAg seroclearance will be reported.	Up to 96 weeks
Percentage of Sustained Clinical Responders	Percentage of sustained clinical responders (those with HBsAg seroclearance) will be reported.	At Week 24, Week 48, and Week 96
Percentage of Participants with HBsAg Seroconversion	Percentage of participants with HBsAg seroconversion will be reported.	At Week 24, Week 48, and Week 96
Percentage of Participants with Serious Adverse Events (SAEs)	SAE is any untoward medical occurrence that results in any of the following conditions that is death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity.	Up to 96 weeks
Percentage of Participants with Abnormalities in Clinical Laboratory Parameters	Percentage of participants with abnormalities in clinical laboratory parameters will be reported.	Up to 96 weeks
Percentage of Participants Who Meet the NA Re-Treatment Criteria	Percentage of participants who meet the NA re-treatment criteria will be reported.	Up to 96 weeks

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutica N.V., Belgium
• Investigators: Study Director: Janssen Pharmaceutica N.V., Belgium Clinical Trial, Janssen Pharmaceutica N.V., Belgium

Study record dates

Study Major Dates

• Study Start (Estimated): October 31, 2022
• Primary Completion (Estimated): August 25, 2025
• Study Completion (Estimated): August 28, 2025

Study Registration Dates

• First Submitted: September 20, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 20, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Hepatitis A; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Entecavir
• Other Study ID Numbers: CR109229; 2021-005588-39 (EudraCT Number); NOPRODHPB0017 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No