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

Hepatitis B, Chronic Clinical Trial

— OCTOPUS-1  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05275023
• Other study ID #: CR109161
• Secondary ID: 2021-005132-3373
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 30, 2022
• Est. completion date: May 30, 2024

Study information

• Verified date: May 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 37
• Est. completion date: May 30, 2024
• Est. primary completion date: December 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• JNJ-73763989
JNJ-73763989 will be administered subcutaneously.
• PD-1 inhibitor
PD-1 inhibitor will be administered as IV infusion.
• Tenofovir Disoproxil
Tenofovir disoproxil film-coated tablets will be administered orally.
• Tenofovir Alafenamide
TAF film-coated tablets will be administered orally.
• Entecavir
ETV film-coated tablets will be administered orally.

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto	Ontario
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	IKEM	Prague 4
France	Hopital Beaujon	Clichy
France	Hopital Saint Joseph	Marseille
France	Chu Rennes Hopital Pontchaillou	Rennes
France	CHRU Nancy Brabois	Vandoeuvre-les-nancy
Italy	Fondazione IRCCS Ca Granda Ospedale Policlinico Di Milano	Milano
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma	Rome
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. Pta. de Hierro Majadahonda	Madrid
Spain	Hosp. Montecelo	Pontevedra
Spain	Hosp. Gral. Univ. Valencia	Valencia
Taiwan	E-DA Hospital	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Ege University Medical Faculty	Izmir
Turkey	Kocaeli University Medical Faculty	Kocaeli
Turkey	Karadeniz Teknik University Medical Faculty	Trabzon
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	Imperial College London and Imperial College Healthcare NHS Trust	London
United Kingdom	King s College Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

Canada,  Czechia,  France,  Italy,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants who Achieve Hepatitis B Surface Antigen (HBsAg) Seroclearance		Follow up Week 24
Secondary	Percentage of Participants who Experience Adverse Events (AEs) of Interest	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.	Up to Week 72
Secondary	Number of Participants with Adverse Events (AEs) by Severity	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.	Up to Week 72
Secondary	Number of Participants with Immune Related Adverse Events (AEs) by Severity	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.	Up to Week 72
Secondary	Number of Participants with Abnormalities in Vital Signs, Physical Examinations, Clinical Laboratory Tests, 12-lead Electrocardiograms (ECGs)	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.	Up to Week 72
Secondary	Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels		Baseline up to Week 72
Secondary	Percentage of Participants with Change in HBsAg Levels Below/Above Different Cut-offs Over Time		Up to Week 72
Secondary	Percentage of Participants with HBsAg Seroclearance/Seroconversion		Up to Week 72
Secondary	Time to Achieve HBsAg Seroclearance/ Seroconversion	Time to achieve HBsAg seroclearance/ seroconversion will be reported.	Up to Week 72
Secondary	Change from Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels		Baseline up to Week 72
Secondary	Percentage of Participants with HBV DNA and Hepatitis B e Antigen (HBeAg) Levels Below/above Different Cut-offs	Percentage of participants with HBV DNA and HBeAg Levels below/above different cut-offs will be reported.	Up to Week 72
Secondary	Percentage of Participants with Virologic Breakthrough	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.	Up to Week 72
Secondary	Plasma Concentrations of JNJ-3989 and its Metabolites (JNJ-3924 and JNJ-3976)	Plasma concentrations of JNJ-3989 and its metabolites (JNJ-3924 and JNJ-3976) will be reported.	Up to Week 24
Secondary	Plasma Concentrations of NA (Tenofovir disoproxil, Tenofovir Alafenamide [TAF] or Entecavir [ETV]) (Optional)	Plasma concentrations of NA (tenofovir disoproxil, TAF or ETV) will be reported.	Up to Week 24
Secondary	Serum Concentrations of PD-1 Inhibitor (Optional)	Serum concentrations of PD-1 inhibitor will be reported.	Up to Week 24