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

Sponsor

Janssen Pharmaceutica N.V., Belgium (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT05550519

Collaborator

(none)

Enrollment

Locations

Arm

33.9

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Other: Entecavir (ETV) Other: Tenofovir Disoproxil Fumarate (TDF) Other: Tenofovir Alafenamide (TAF)	Early Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

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

Anticipated Study Start Date :

Oct 31, 2022

Anticipated Primary Completion Date :

Aug 25, 2025

Anticipated Study Completion Date :

Aug 28, 2025

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Percentage of Participants with Flares [At Week 24, Week 48, and Week 96]
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.
Change from Baseline Over Time in HBsAg Level [Baseline up to 96 weeks]
Change from baseline over time in HBsAg level will be reported.
Change from Baseline Over Time in HBV DNA level [Baseline up to 96 weeks]
Change from baseline over time in HBV DNA level will be reported.
Time to Achieve First HBsAg Seroclearance [Up to 96 weeks]
Time to achieve first HBsAg seroclearance will be reported.
Percentage of Sustained Clinical Responders [At Week 24, Week 48, and Week 96]
Percentage of sustained clinical responders (those with HBsAg seroclearance) will be reported.
Percentage of Participants with HBsAg Seroconversion [At Week 24, Week 48, and Week 96]
Percentage of participants with HBsAg seroconversion will be reported.
Percentage of Participants with Serious Adverse Events (SAEs) [Up to 96 weeks]
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.
Percentage of Participants with Abnormalities in Clinical Laboratory Parameters [Up to 96 weeks]
Percentage of participants with abnormalities in clinical laboratory parameters will be reported.
Percentage of Participants Who Meet the NA Re-Treatment Criteria [Up to 96 weeks]
Percentage of participants who meet the NA re-treatment criteria will be reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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