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 (OCTOPUS-1)

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: JNJ-73763989; Drug: PD-1 inhibitor; Drug: Tenofovir Disoproxil; Drug: Tenofovir Alafenamide; Drug: Entecavir

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).

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultni Nemocnice Hradec Kralove
  • Prague 4, Czechia, 140 21
    • IKEM
• France
  • Clichy, France, 92110
    • Hôpital Beaujon
  • Marseille, France, 13008
    • Hopital Saint Joseph
  • Rennes, France, 35000
    • Chu Rennes Hopital Pontchaillou
  • Vandoeuvre-les-nancy, France, 54500
    • Chru Nancy Brabois
• Italy
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Policlinico Di Milano
  • Pisa, Italy, 56124
    • Azienda Ospedaliero Universitaria Pisana
  • Rome, Italy, 00161
    • Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma
• Spain
  • Barcelona, Spain, 8035
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28222
    • Hosp. Univ. Pta. de Hierro Majadahonda
  • Pontevedra, Spain, 36071
    • Hosp. Montecelo
  • Valencia, Spain, 46014
    • Hosp. Gral. Univ. Valencia
• Taiwan
  • Kaohsiung, Taiwan, 824
    • E-DA Hospital
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Medical University Chung Ho Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taoyuan, Taiwan, 33305
    • Linkou Chang Gung Memorial Hospital
• Turkey
  • Ankara, Turkey, 06230
    • Hacettepe University Medical Faculty
  • Istanbul, Turkey, 34098
    • Istanbul University Cerrahpasa Medical Faculty
  • Izmir, Turkey, 35040
    • Ege University Medical Faculty
  • Kocaeli, Turkey, 41001
    • Kocaeli University Medical Faculty
  • Trabzon, Turkey, 61080
    • Karadeniz Teknik University Medical Faculty
• United Kingdom
  • Glasgow, United Kingdom, G31 2ER
    • Glasgow Royal Infirmary
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • London, United Kingdom, W2 1NY
    • Imperial College London and Imperial College Healthcare NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA); 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]).	Drug: JNJ-73763989; JNJ-73763989 will be administered subcutaneously.; Other Names: JNJ-3989; Drug: PD-1 inhibitor; PD-1 inhibitor will be administered as IV infusion.; Drug: Tenofovir Disoproxil; Tenofovir disoproxil film-coated tablets will be administered orally.; Drug: Tenofovir Alafenamide; TAF film-coated tablets will be administered orally.; Drug: Entecavir; ETV film-coated tablets will be administered orally.
Experimental: Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA; 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).	Drug: JNJ-73763989; JNJ-73763989 will be administered subcutaneously.; Other Names: JNJ-3989; Drug: PD-1 inhibitor; PD-1 inhibitor will be administered as IV infusion.; Drug: Tenofovir Disoproxil; Tenofovir disoproxil film-coated tablets will be administered orally.; Drug: Tenofovir Alafenamide; TAF film-coated tablets will be administered orally.; Drug: Entecavir; ETV film-coated tablets will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Hepatitis B Surface Antigen (HBsAg) Seroclearance at Follow-up (FU) Week 24	Percentage of participants who achieved HBsAg seroclearance at FU Week 24 were reported. Seroclearance of HBsAg was defined as a (quantitative) HBsAg level less than (<) lower limit of quantification (LLOQ) (0.05 international unit per milliliters [IU/mL]).	At FU Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) of Special Interest	An AE was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily had a causal relationship with the pharmaceutical/biological agent under study. Any AE occurring at or after the initial administration of study intervention was considered to be treatment emergent. AEs of interest were significant AEs that are judged to be of special interest because of clinical importance, known class effects or based on nonclinical signals.	IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
Number of Participants With TEAEs by Severity	Number of participants with TEAEs by severity were reported. An AE was any untoward medical occurrence in a participant participating in a clinical study that did not necessarily had a causal relationship with the pharmaceutical/biological agent under study. Any AE occurring at or after the initial administration of study intervention was considered to be treatment emergent. Severity of AE were graded by using Division of Acquired Immunodeficiency Syndrome (DAIDS) grading scale that 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 indicated a potentially life-threatening event, Grade 5 indicated death.	IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
Number of Participants With Immune Related TEAEs	Number of participants with immune related TEAEs were reported. An AE was any untoward medical occurrence in a participant participating in a clinical study that did not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Any AE occurring at or after the initial administration of study intervention was considered to be treatment emergent. Immune-related AEs (irAEs) were alanine aminotransferase/alanine aminotransferase (ALT/AST) elevations including immune-related hepatic AEs, infusion-related reaction (IRRs) and other irAEs (including gastrointestinal AEs, neurological AEs, pulmonary AEs, renal AEs, endocrinopathies, rash, uveitis and visual complaints, lipase/amylase elevations, and infection), hematological abnormalities and injection site reactions.	IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
Number of Participants With Abnormalities in Vital Signs	Number of participants with abnormalities in vital signs measurements (including pulse rate: abnormally low: less than or equal to [<=] 45 beats per minute [bpm], abnormally high: greater than or equal to [>=] 120 bpm; diastolic blood pressure [BP]: abnormally low: <=50 millimeters of mercury [mmHg], mild: >90 to <100 mmHg, moderate: >=100 to <110 mmHg, and severe: >=110 mmHg; systolic BP: abnormally low: <=90 mmHg, mild: >140 to <160 mmHg, moderate: >=160 to <180 mmHg, and severe: >=180 mmHg) were reported.	IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
Number of Participants With Abnormalities in 12-lead Electrocardiogram (ECGs)	Number of participants with abnormalities in 12-lead ECGs: heart rate (abnormally low: <45 beats per minute [bpm], abnormally high: greater than or equal [>=] 120 bpm), PR interval (abnormally high: greater than [>] 220 millisecond [msec]), QRS interval (abnormally high: >=120 msec), QTc interval Fridericia (Borderline prolonged QT: 450< QTc <=480 msec; Prolonged QT: 480 < QTc <=500; Pathologically prolonged QT: QTc >500) were reported.	IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
Number of Participants With Abnormalities in Physical Examinations	Number of participants with abnormalities in physical examinations were reported.	IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
Percentage of Participants With Abnormalities in Clinical Laboratory Parameters: Hematology	Percentage of participants with abnormalities in hematology parameters (including basophils/Leukocytes high, erythrocytes mean corpuscular volume high, erythrocytes high and low, lymphocytes/leukocytes high and low, monocytes/leukocytes high and low, neutrophils, segmented+band form high and low, reticulocytes/erythrocytes high and low, basophils/leukocytes, eosinophils/leukocytes high, erythrocyte mean corpuscular hemoglobin low, reticulocytes/erythrocytes high and low, lymphocytes atypical/leukocytes high, lymphocytes atypical high, hematocrit high, monocytes low and high) were reported. Abnormalities with at least 1 participant is included. Low and high categorization depend on investigator's discretion.	IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
Number of Participants With Abnormalities in Clinical Laboratory Parameters: Clinical Chemistry	Number of participants with abnormalities in clinical chemistry parameters (including C reactive protein high, cystatin C low and high, gamma glutamyl transferase low, high density lipoprotein [HDL] cholesterol low and high, indirect bilirubin high, lactate dehydrogenase high, protein high, thyrotropin low and high, free thyroxine high, free triiodothyronine low and high, and urea nitrogen high) were reported. Abnormalities with at least 1 participant is included. Low and high categorization depend on investigator's discretion.	IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
Number of Participants With Abnormalities in Clinical Laboratory Parameters: Urinalysis	Number of participants with abnormalities in clinical laboratory parameters (including specific gravity high and urine hyaline casts high) were reported. Abnormalities with at least 1 participant is included. Low and high categorization depend on investigator's discretion.	IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48
Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels	Change from baseline in HBsAg levels were reported. International units per milliliters=IU/mL. End of Study Intervention (EOSI) was the last post-baseline visit in study intervention period. End of study (EOS) was the last visit in the study.	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)
Percentage of Participants With Change in HBsAg Levels Below/Above Different Cut-offs Over Time	Percentage of participants with change in HBsAg levels below/above different cut-offs (<0.05 IU/mL, <1 U/mL, <10 IU/mL, <100 IU/mL , <1000 IU/mL) over time were reported. EOSI was the last post-baseline visit in study intervention period. EOS was the last visit in the study.	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)
Percentage of Participants With HBsAg Seroclearance	Percentage of participants with HBsAg seroclearance were reported. Seroclearance of HBsAg was defined as a HBsAg level <lower limit of quantification (LLOQ) (0.05 IU/mL).	IP: Week 0 to Week 24; FU Phase: FU Week 1 up to FU Week 48
Percentage of Participants With HBsAg Seroconversion	Percentage of participants with HBsAg seroconversion were reported. Seroconversion of HBsAg was defined as having achieved HBsAg seroclearance and appearance of anti-HBs antibodies (baseline anti-HBs antibodies <LLOQ and a post-baseline assessment >=LLOQ).	IP: Week 0 to Week 24; FU Phase: FU Week 1 up to FU Week 48
Time to Achieve HBsAg Seroclearance	Time to achieve HBsAg seroclearance was reported. Seroclearance of HBsAg was defined as a (quantitative) HBsAg level <LLOQ (0.05 IU/mL).	Week 0 up to FU Week 48 (up to Week 72)
Time to Achieve HBsAg Seroconversion	Time to achieve HBsAg seroconversion were reported. Seroconversion of HBsAg was defined as having achieved HBsAg seroclearance and appearance of anti-HBs antibodies (baseline anti-HBs antibodies <LLOQ and a post-baseline assessment >=LLOQ).	Week 0 up to FU Week 48 (up to Week 72)
Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels Over Time	HBV DNA levels over time were reported. EOSI was the last post-baseline visit in study intervention period. EOS was the last visit in the study.	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)
Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Level Below/Above Different Cut-offs Over Time	Percentage of participants with HBV DNA level below/above different cut-offs over time were reported. HBV DNA cut offs: <LLOQ target detected (TD): that is, traces of HBV DNA were detected/found but were too low to be quantified; <LLOQ target not detected (TND): that is, no traces of HBV DNA were detected/found. EOSI was the last post-baseline visit in study intervention period. EOS was the last visit in the study. The LLOQ for HBV DNA was 20 IU/mL. As indicated in the data table, the sum of percentage values of each sub-categories within the specific timepoints "IP: Week 2" and "FU Phase: Week 4", shows a slight deviation from 100% due to rounding.	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)
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Level Below/Above Different Cut-offs Over Time	Percentage of participants with HBeAg level below/above different cut-offs over time were reported. HBeAg cut-offs: <LLOQ (0.11 IU/mL). EOSI was the last post-baseline visit in study intervention period. EOS was the last visit in the study.	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)
Percentage of Participants With Virologic Breakthrough	Percentage of participants with virologic breakthrough (confirmed on-treatment HBV DNA increase by >1 log10 IU/mL from nadir in participants who did not have on-treatment HBV DNA level below LLOQ or a confirmed on-treatment HBV DNA level >200 IU/mL in participants who had on-treatment HBV DNA level below LLOQ) were reported.	IP: Week 0 to Week 24; FU Phase: FU Week 1 up to FU Week 48

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2022
• Primary Completion (Actual): December 12, 2023
• Study Completion (Actual): May 31, 2024

Study Registration Dates

• First Submitted: March 2, 2022
• First Submitted That Met QC Criteria: March 2, 2022
• First Posted (Actual): March 11, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Hepatitis A; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Antineoplastic Agents, Immunological; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Immune Checkpoint Inhibitors; Entecavir
• Other Study ID Numbers: CR109161; 2021-005132-33 (EudraCT Number); 73763989PAHPB2008 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes