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
- Conditions
- Hepatitis B, Chronic
- Interventions
- Drug: JNJ-73763989Drug: PD-1 inhibitorDrug: Tenofovir DisoproxilDrug: Tenofovir AlafenamideDrug: Entecavir
- Registration Number
- NCT05275023
- Lead Sponsor
- Janssen Research & Development, LLC
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA PD-1 inhibitor Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV). Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA) JNJ-73763989 Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide \[TAF\] or entecavir \[ETV\]). Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA JNJ-73763989 Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV). Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA) PD-1 inhibitor Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide \[TAF\] or entecavir \[ETV\]). Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA Tenofovir Alafenamide Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV). Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA) Tenofovir Disoproxil Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide \[TAF\] or entecavir \[ETV\]). Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA) Entecavir Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide \[TAF\] or entecavir \[ETV\]). Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA) Tenofovir Alafenamide Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide \[TAF\] or entecavir \[ETV\]). Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA Tenofovir Disoproxil Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV). Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA Entecavir Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV).
- Primary Outcome Measures
Name Time Method Percentage of Participants who Achieve Hepatitis B Surface Antigen (HBsAg) Seroclearance Follow up Week 24
- Secondary Outcome Measures
Name Time Method Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels Baseline up to Week 72 Percentage of Participants with Change in HBsAg Levels Below/Above Different Cut-offs Over Time Up to Week 72 Change from Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels Baseline up to Week 72 Plasma Concentrations of NA (Tenofovir disoproxil, Tenofovir Alafenamide [TAF] or Entecavir [ETV]) (Optional) Up to Week 24 Plasma concentrations of NA (tenofovir disoproxil, TAF or ETV) will be reported.
Time to Achieve HBsAg Seroclearance/ Seroconversion Up to Week 72 Time to achieve HBsAg seroclearance/ seroconversion will be reported.
Percentage of Participants with HBV DNA and Hepatitis B e Antigen (HBeAg) Levels Below/above Different Cut-offs Up to Week 72 Percentage of participants with HBV DNA and HBeAg Levels below/above different cut-offs will be reported.
Number of Participants with Abnormalities in Vital Signs, Physical Examinations, Clinical Laboratory Tests, 12-lead Electrocardiograms (ECGs) Up to Week 72 Number of participants with abnormalities in vital sign measurements (including pulse rate and blood pressure, both systolic and diastolic); physical examinations (including height at screening, body weight, skin examination, general appearance, eyes, ears, nose, throat, cardiovascular system, respiratory system, gastro-intestinal system and mucous; clinical laboratory tests (including hematology, clinical chemistry and urinalysis); 12-lead ECGs (heart rate, PR, QRS, QT) will be reported.
Serum Concentrations of PD-1 Inhibitor (Optional) Up to Week 24 Serum concentrations of PD-1 inhibitor will be reported.
Percentage of Participants who Experience Adverse Events (AEs) of Interest Up to Week 72 An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. AEs of interest are significant AEs that are judged to be of special interest because of clinical importance, known class effects or based on nonclinical signals.
Number of Participants with Immune Related Adverse Events (AEs) by Severity Up to Week 72 An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of immune related AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Percentage of Participants with HBsAg Seroclearance/Seroconversion Up to Week 72 Percentage of Participants with Virologic Breakthrough Up to Week 72 Percentage of participants with virologic breakthrough (confirmed on-treatment HBV DNA increase by greater than \[\>\]1 log10 international unit per milliliter \[IU/mL\] from nadir or confirmed on-treatment HBV DNA level \>200 IU/mL in participants who had HBV DNA level less than \[\<\] lower limit of quantification \[LLOQ\] of the HBV DNA assay) will be reported.
Number of Participants with Adverse Events (AEs) by Severity Up to Week 72 An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity of adverse event will be graded by using Division of AIDS (DAIDS) grading scale ranges from Grade 1 to Grade 5. Grade 1 indicates a mild event, Grade 2 indicates a moderate event, Grade 3 indicates a severe event, Grade 4 indicates a potentially life-threatening event, Grade 5 indicates death.
Plasma Concentrations of JNJ-3989 and its Metabolites (JNJ-3924 and JNJ-3976) Up to Week 24 Plasma concentrations of JNJ-3989 and its metabolites (JNJ-3924 and JNJ-3976) will be reported.
Trial Locations
- Locations (26)
Hosp. Univ. Pta. de Hierro Majadahonda
🇪🇸Madrid, Spain
Imperial College London and Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Hopital Beaujon
🇫🇷Clichy, France
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma
🇮🇹Rome, Italy
China Medical University Hospital
🇨🇳Taichung, Taiwan
Karadeniz Teknik University Medical Faculty
🇹🇷Trabzon, Turkey
Hopital Saint Joseph
🇫🇷Marseille, France
Linkou Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
IKEM
🇨🇿Prague 4, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Chu Rennes Hopital Pontchaillou
🇫🇷Rennes, France
Fondazione IRCCS Ca Granda Ospedale Policlinico Di Milano
🇮🇹Milano, Italy
CHRU Nancy Brabois
🇫🇷Vandoeuvre-les-nancy, France
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Istanbul University Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Hosp. Montecelo
🇪🇸Pontevedra, Spain
Hosp. Gral. Univ. Valencia
🇪🇸Valencia, Spain
E-DA Hospital
🇨🇳Kaohsiung, Taiwan
Kaohsiung Medical University Chung Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Kocaeli University Medical Faculty
🇹🇷Kocaeli, Turkey
Ege University Medical Faculty
🇹🇷Izmir, Turkey
Glasgow Royal Infirmary
🇬🇧Glasgow, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom