Clinical trial NCT05550519: A Study in Chronic Hepatitis B e-Antigen Negative Participants After Discontinuation of Nucleos(t)Ide Analog (NA) Treatment
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Hepatitis B, Chronic
Lead sponsor: Janssen Pharmaceutica N.V., Belgium
Sponsor class: INDUSTRY
First posted: 2022-09-22
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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).

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

Primary outcomes:
measure: Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance After Discontinuation of Nucleos(t)ide Analog (NA) Treatment
timeFrame: At Week 24
measure: Percentage of Participants with HBsAg Seroclearance After Discontinuation of NA Treatment
timeFrame: At Week 48
measure: Percentage of Participants with HBsAg Seroclearance After Discontinuation of NA Treatment
timeFrame: At Week 96
Secondary outcomes:
measure: Percentage of Participants with Flares
timeFrame: At Week 24, Week 48, and Week 96
measure: Change from Baseline Over Time in HBsAg Level
timeFrame: Baseline up to 96 weeks
measure: Change from Baseline Over Time in HBV DNA level
timeFrame: Baseline up to 96 weeks
measure: Time to Achieve First HBsAg Seroclearance
timeFrame: Up to 96 weeks
measure: Percentage of Sustained Clinical Responders
timeFrame: At Week 24, Week 48, and Week 96
measure: Percentage of Participants with HBsAg Seroconversion
timeFrame: At Week 24, Week 48, and Week 96
measure: Percentage of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to 96 weeks
measure: Percentage of Participants with Abnormalities in Clinical Laboratory Parameters
timeFrame: Up to 96 weeks
measure: Percentage of Participants Who Meet the NA Re-Treatment Criteria
timeFrame: Up to 96 weeks
Other outcomes:
Locations:
city: Kolding
country: Denmark
facility: Sygehus Lillebælt - Kolding Sygehus
city: Odense
country: Denmark
facility: Odense Universitets Hospital
city: Roskilde
country: Denmark
facility: Sjællands University hospital
city: Bobigny
country: France
facility: Hôpital Avicenne
city: La Tronche
country: France
facility: CHU Grenoble
city: Lyon
country: France
facility: Hopital de La Croix Rousse
city: Rennes cedex 9
country: France
facility: Hopital Pontchaillou
city: Frankfurt
country: Germany
facility: Universitatsklinikum Frankfurt
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: Leipzig
country: Germany
facility: Klinikum Sankt Georg Neurologie
city: Tübingen
country: Germany
facility: Eberhard Karls Universität Tübingen
city: Athens
country: Greece
facility: G.H. of Athens Evangelismos
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki Ippokrateio
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
city: Foggia
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: San Giovanni Rotondo
country: Italy
facility: Casa Sollievo della Sofferenza
city: Torino
country: Italy
facility: Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino
city: Braga
country: Portugal
facility: Hosp. Sra. Da Oliveira - Guimaraes
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitario de Coimbra
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Norte - Hospital Santa Maria
city: Vila Real
country: Portugal
facility: Centro Hospitalar de Trás os Montes e Alto Douro- Vila Real
city: Barcelona
country: Spain
facility: Hosp. Del Mar
city: Barcelona
country: Spain
facility: Hosp. Clinic I Provincial de Barcelona
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: València
country: Spain
facility: Hosp. Clinico Univ. de Valencia
Study officials:
affiliation: Janssen Pharmaceutica N.V., Belgium
name: Janssen Pharmaceutica N.V., Belgium Clinical Trial
role: STUDY_DIRECTOR
References: