Clinical trial NCT05275023: An Efficacy and Safety Study of a Combination of JNJ-73763989, Nucleos(t)Ide Analogs (NA), and a Programmed Cell Death Protein Receptor-1 (PD-1) Inhibitor in Chronic Hepatitis B Participants
Official title: A Phase 2 Open-label Trial to Evaluate Safety, Efficacy, Tolerability, and Pharmacodynamics of a Combination of JNJ-73763989, Nucleos(t)Ide Analogs, and a PD-1 Inhibitor in Chronic Hepatitis B Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-03-11
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate efficacy of the study intervention, based on hepatitis B surface antigen (HBsAg) levels at follow-up (FU) Week 24.

Detailed description: JNJ-73763989 (JNJ-3989) is a small interfering ribonucleic acid (siRNA) targeting all hepatitis B virus (HBV) messenger ribonucleic acid (mRNAs). The programmed cell death protein receptor-1 (PD-1) inhibitor aims at preventing the interaction of PD-1 with its ligands. The purpose of this study to determine whether at least one of the combination regimens of JNJ-3989 + PD-1 inhibitor + Nucleos(t)ide analog (NA) is more efficacious than JNJ-3989 + NA treatment. This study will be conducted in 3 periods: screening period, treatment period and follow-up (FU) period. Safety assessments will include adverse events (AEs), serious AEs, clinical safety laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. Total duration of individual participation will be up to 78 weeks (including screening period).

Eligibility criteria: Inclusion Criteria:

* Participants must have chronic hepatitis B virus (HBV) infection
* Participants must have fibroscan liver stiffness measurement less than or equal to (\<=) 9.0 kilopascal (kPa) or a liver biopsy result classified as metavir F0-F2

Exclusion Criteria:

* Participants with evidence of hepatitis A virus infection (hepatitis A antibody immunoglobulin IgM), hepatitis C virus (HCV) infection (HCV antibody), hepatitis D virus (HDV) infection (HDV antibody), hepatitis E virus (HEV) infection (hepatitis E antibody IgM), or human immunodeficiency virus type 1 (HIV-1) or human immunodeficiency virus type 2 (HIV-2) infection (laboratory confirmed) at screening
* History or evidence of clinical signs or symptoms of hepatic decompensation, including but not limited to portal hypertension, ascites, hepatic encephalopathy, esophageal varices
* Participants with history or signs of cirrhosis or portal hypertension or signs of hepatocellular carcinoma (HCC) or clinically relevant renal abnormalities
* Participants with personal/familial history/indicative of immune-mediated disease risk

Primary outcomes:
measure: Percentage of Participants Who Achieved Hepatitis B Surface Antigen (HBsAg) Seroclearance at Follow-up (FU) Week 24
timeFrame: At FU Week 24
Secondary outcomes:
measure: Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) of Special Interest
timeFrame: IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
measure: Number of Participants With TEAEs by Severity
timeFrame: IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
measure: Number of Participants With Immune Related TEAEs
timeFrame: IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
measure: Number of Participants With Abnormalities in Vital Signs
timeFrame: IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
measure: Number of Participants With Abnormalities in 12-lead Electrocardiogram (ECGs)
timeFrame: IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
measure: Number of Participants With Abnormalities in Physical Examinations
timeFrame: IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
measure: Percentage of Participants With Abnormalities in Clinical Laboratory Parameters: Hematology
timeFrame: IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
measure: Number of Participants With Abnormalities in Clinical Laboratory Parameters: Clinical Chemistry
timeFrame: IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
measure: Number of Participants With Abnormalities in Clinical Laboratory Parameters: Urinalysis
timeFrame: IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
measure: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels
timeFrame: IP: Baseline, Weeks 1, 2, 3, 4, 8, 12, 16, 20, and End of Study Intervention (EOSI; Week 24); FU Phase: FU Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, and EOS (last visit at FU Week 48)
measure: Percentage of Participants With Change in HBsAg Levels Below/Above Different Cut-offs Over Time
timeFrame: IP: Baseline, Weeks 1, 2, 3, 4, 8, 12, 16, 20, and EOSI (Week 24); FU Phase: FU Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, and EOS (last visit at FU Week 48)
measure: Percentage of Participants With HBsAg Seroclearance
timeFrame: IP: Week 0 to Week 24; FU Phase: FU Week 1 up to FU Week 48
measure: Percentage of Participants With HBsAg Seroconversion
timeFrame: IP: Week 0 to Week 24; FU Phase: FU Week 1 up to FU Week 48
measure: Time to Achieve HBsAg Seroclearance
timeFrame: Week 0 up to FU Week 48 (up to Week 72)
measure: Time to Achieve HBsAg Seroconversion
timeFrame: Week 0 up to FU Week 48 (up to Week 72)
measure: Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels Over Time
timeFrame: IP: Baseline, Weeks 2, 4, 8, 12, 16, 20 and EOSI (Week 24); FU Phase: FU Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, and EOS (last visit at FU Week 48)
measure: Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Level Below/Above Different Cut-offs Over Time
timeFrame: IP: Baseline, Weeks 2, 4, 8, 12, 16, 20, and EOSI (Week 24); FU Phase: FU Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, and EOS (last visit at FU Week 48)
measure: Percentage of Participants With Hepatitis B e Antigen (HBeAg) Level Below/Above Different Cut-offs Over Time
timeFrame: IP: Baseline, Weeks 2, 4, 8, 12, 20, and EOSI (Week 24); FU Phase: FU Weeks 12, 16, 20, 24, 32, 40, 48, and EOS (last visit at FU Week 48)
measure: Percentage of Participants With Virologic Breakthrough
timeFrame: IP: Week 0 to Week 24; FU Phase: FU Week 1 up to FU Week 48
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Prague 4
country: Czechia
facility: IKEM
city: Clichy
country: France
facility: Hopital Beaujon
city: Marseille
country: France
facility: Hopital Saint Joseph
city: Rennes
country: France
facility: Chu Rennes Hopital Pontchaillou
city: Vandoeuvre-les-nancy
country: France
facility: CHRU Nancy Brabois
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Policlinico Di Milano
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Rome
country: Italy
facility: Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Univ. Pta. de Hierro Majadahonda
city: Pontevedra
country: Spain
facility: Hosp. Montecelo
city: Valencia
country: Spain
facility: Hosp. Gral. Univ. Valencia
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: E-DA Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Kocaeli
country: Turkey
facility: Kocaeli University Medical Faculty
city: Trabzon
country: Turkey
facility: Karadeniz Teknik University Medical Faculty
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: Imperial College London and Imperial College Healthcare NHS Trust
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: