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

Hepatitis B, Chronic Clinical Trial

— SALMONS  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05550519
• Other study ID #: CR109229
• Secondary ID: 2021-005588-39NO
• Status: Withdrawn
• Phase: Early Phase 1
• Start date: October 31, 2022
• Est. completion date: August 28, 2025

Study information

• Verified date: October 2022
• Source: Janssen Pharmaceutica N.V., Belgium
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 28, 2025
• Est. primary completion date: August 25, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

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

Locations

Country	Name	City	State
Denmark	Sygehus Lillebælt - Kolding Sygehus	Kolding
Denmark	Odense Universitets Hospital	Odense
Denmark	Sjællands University hospital	Roskilde
France	Hôpital Avicenne	Bobigny
France	CHU Grenoble	La Tronche
France	Hopital de La Croix Rousse	Lyon
France	Hopital Pontchaillou	Rennes cedex 9
Germany	Universitatsklinikum Frankfurt	Frankfurt
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Klinikum Sankt Georg Neurologie	Leipzig
Germany	Universitatsklinikum Leipzig	Leipzig
Germany	Eberhard Karls Universität Tübingen	Tübingen
Greece	G.H. of Athens Evangelismos	Athens
Greece	Laiko General Hospital of Athens	Athens
Greece	General Hospital of Thessaloniki Ippokrateio	Thessaloniki
Italy	ASST Spedali Civili di Brescia	Brescia
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia	Foggia
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara	Modena
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Casa Sollievo della Sofferenza	San Giovanni Rotondo
Italy	Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino	Torino
Portugal	Hosp. Sra. Da Oliveira - Guimaraes	Braga
Portugal	Centro Hospitalar e Universitario de Coimbra	Coimbra
Portugal	Centro Hospitalar de Lisboa Norte - Hospital Santa Maria	Lisboa
Portugal	Centro Hospitalar de Trás os Montes e Alto Douro- Vila Real	Vila Real
Spain	Hosp. Clinic I Provincial de Barcelona	Barcelona
Spain	Hosp. Del Mar	Barcelona
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Spain	Hosp. Clinico Univ. de Valencia	València

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutica N.V., Belgium

Countries where clinical trial is conducted

Denmark,  France,  Germany,  Greece,  Italy,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	Change from Baseline Over Time in HBsAg Level	Change from baseline over time in HBsAg level will be reported.	Baseline up to 96 weeks
Secondary	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
Secondary	Time to Achieve First HBsAg Seroclearance	Time to achieve first HBsAg seroclearance will be reported.	Up to 96 weeks
Secondary	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
Secondary	Percentage of Participants with HBsAg Seroconversion	Percentage of participants with HBsAg seroconversion will be reported.	At Week 24, Week 48, and Week 96
Secondary	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
Secondary	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
Secondary	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