A Study of JNJ 73763989+JNJ 56136379+Nucleos(t)Ide Analog (NA) Regimen Compared to NA Alone in e Antigen Negative Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection

A Randomized, Double Blind, Placebo-controlled Phase 2b Study to Evaluate Efficacy, Pharmacokinetics, and Safety of 48-week Study Intervention With JNJ 73763989+JNJ 56136379+Nucleos(t)Ide Analog (NA) Regimen Compared to NA Alone in e Antigen Negative Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection

The purpose of this study is to evaluate the efficacy of 48-week study intervention with JNJ-73763989+JNJ-56136379+nucleos(t)ide analog (NA) regimen compared to NA alone assessed by HBsAg levels. This study is part of HepB Wings Platform Trial (PLATFORMPAHPB2001).

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: JNJ-56136379; Drug: Tenofovir alafenamide (TAF); Drug: JNJ-73763989; Drug: Entecavir (ETV) monohydrate; Drug: Tenofovir disoproxil fumarate (TDF); Drug: Placebo for JNJ-73763989; Drug: Placebo for JNJ-56136379

Detailed Description

Hepatitis B virus (HBV) is a small deoxyribonucleic acid (DNA) virus that infects the liver and can cause either acute or chronic infection. It consists of a so-called nucleocapsid in which viral DNA is packed with hepatitis B core protein (HBc) and membranous envelope containing hepatitis B surface antigen (HBsAg). Chronic HBV infection may lead to serious illnesses like cirrhosis and hepatocellular carcinoma (HCC). Oral treatment with NAs is effective at suppressing viral DNA formation and lowering virus concentration in blood to levels below lower limit of quantification (LLOQ). JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via ribonucleic acid interference mechanism but rarely lead to functional cure defined as sustained loss of HBs Ag and HBV DNA in serum. JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for treatment of chronic HBV infection. The aim of study is to evaluate efficacy of 48-week study intervention with JNJ-3989+JNJ-6379+NA regimen compared to NA alone, assessed by HBsAg seroclearance at Week 72 (i.e., 24 weeks after completion of all study interventions at Week 48) without restarting NA treatment in HBeAg negative virologically suppressed chronic hepatitis B (CHB) infected participants who received NA treatment for at least 2 years prior to screening. The study will be 2.3 years and will be conducted in 3 phases: a screening phase (4 weeks), a study intervention phase (48 weeks), and a follow-up phase (48 weeks). Safety will be evaluated by AEs including AEs of special interest to any of the study interventions, clinical laboratory tests, ECGs, vital signs, and physical examinations.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Edegem, Belgium, 2650
    • SGS Belgium NV
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
• France
  • Clichy, France, 92110
    • Hopital Beaujon
  • Lyon, France, 69004
    • Hôpital de La Croix Rousse
  • Marseille, France, 13008
    • Hopital Saint Joseph
  • Paris, France, 75014
    • Hôpital Cochin
  • Rennes, France, 35033
    • CHU Rennes - Hopital Pontchaillou
  • Vandoeuvre les Nancy, France, 54511
    • CHU Nancy Brabois
  • Villejuif, France, 94800
    • Hopital Paul Brousse
• Germany
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg
  • Hamburg, Germany, 20146
    • ICH Study Center GmbH & Co. KG
  • Hamburg, Germany, D-20246
    • University Medical Center
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig
  • Mainz, Germany, 55121
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
• Italy
  • Messina, Italy, 98124
    • Azienda Ospedaliera Universitaria Policlinico G. Martino
  • Milano, Italy, 20122
    • Irccs Ospedale Maggiore Di Milano
  • Modena, Italy, 41126
    • Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara
  • Pisa, Italy, 56124
    • Azienda Ospedaliero Universitaria Pisana
  • Rome, Italy, 00161
    • Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma
• Poland
  • Bydgoszcz, Poland, 85-030
    • Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy
  • Gdansk, Poland, 80-462
    • Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska
  • Myslowice, Poland, 41-400
    • ID Clinic
  • Wroclaw, Poland, 50-136
    • SP ZOZ Wroclawskie Centrum Zdrowia
• Spain
  • Barcelona, Spain, 8035
    • Hosp. Univ. Vall D Hebron
  • Barcelona, Spain, 8028
    • Hosp. Clinic I Provincial de Barcelona
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28222
    • Hosp. Univ. Pta. de Hierro Majadahonda
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
  • Valencia, Spain, 46014
    • Hosp. Gral. Univ. Valencia
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • Crumpsall, United Kingdom, M8 5RB
    • North Manchester General Hospital
  • Glasgow, United Kingdom, G31 2ER
    • Glasgow Royal Infirmary
  • London, United Kingdom, E1 1BB
    • Grahame Hayton Unit
  • London, United Kingdom, SE5 9RF
    • Kings College Hospital
  • London, United Kingdom, SW17 0RE
    • St George's, University of London and St George's University Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
• Chronic hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening
• Hepatitis B e (antigen) (HBeAg)-negative on stable nucleotide analogue (NA) treatment for at least 24 months prior to screening
• Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
• Body mass index (BMI) between 18.0 and 35 kilogram per meter square (kg/m^2), extremes included
• Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
• Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than (<) 9 Kilopascal (kPa) at screening

Exclusion Criteria:

• Evidence of infection with hepatitis A, C, D or E virus infection or evidence of human immunodeficiency, virus type 1 (HIV-1) or HIV-2 infection at screening
• History or evidence of clinical signs/symptoms of hepatic decompensation including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices or any laboratory abnormalities indicating a reduced liver function as defined in the protocol
• Evidence of liver disease of non-HBV etiology
• History or signs of cirrhosis or portal hypertension (nodules, no smooth liver contour, no normal portal vein, spleen size ≥12 cm) or signs of hepatocellular carcinoma (HCC)
• Significant laboratory abnormalities as defined in the protocol at screening
• Participants with a history of malignancy within 5 years before screening
• Abnormal sinus rhythm or ECG parameters at screening as defined in the protocol
• History of or current cardiac arrhythmia or history or clinical evidence of significant or unstable cardiac disease
• Participants with any current or previous illness for which, in the opinion of the investigator and/or sponsor, participation would not be in the best interest of the participant
• History of or current clinically significant skin disease or drug rash
• Known allergies, hypersensitivity, or intolerance to JNJ-73763989 and JNJ-56136379 or their excipients or to placebo content
• Contraindications to the use of entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) per local prescribing information
• Participants who have taken any therapies disallowed per protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNJ-73763989+ JNJ-56136379+ NA; Participants will receive fixed dose of JNJ-73763989 subcutaneous injection once every 4 weeks along with fixed dose of JNJ-56136379 tablet once daily and nucleos(t)ide analog (NA) treatment (either entecavir [ETV], tenofovir disoproxil fumarate [TDF], or tenofovir alafenamide [TAF]) once daily up to 48 weeks.	Drug: JNJ-56136379; JNJ-56136379 tablets will be administered orally once daily up to 48 weeks.; Drug: Tenofovir alafenamide (TAF); TAF will be administered orally once daily up to 48 weeks as NA treatment.; Drug: JNJ-73763989; JNJ-73763989 injection will be administered subcutaneously once every 4 weeks up to 48 weeks.; Drug: Entecavir (ETV) monohydrate; ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.; Drug: Tenofovir disoproxil fumarate (TDF); TDF will be administered orally once daily up to 48 weeks as NA treatment.
Placebo Comparator: Placebo for JNJ-73763989+ Placebo for JNJ-56136379+ NA; Participants will receive matching placebo for JNJ-73763989 subcutaneous injection once every 4 weeks with matching placebo for JNJ-56136379 once daily and NA treatment (either ETV, TDF or TAF) once daily up to 48 weeks.	Drug: Tenofovir alafenamide (TAF); TAF will be administered orally once daily up to 48 weeks as NA treatment.; Drug: Entecavir (ETV) monohydrate; ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.; Drug: Tenofovir disoproxil fumarate (TDF); TDF will be administered orally once daily up to 48 weeks as NA treatment.; Drug: Placebo for JNJ-73763989; Matching placebo for JNJ-73763989 will be administered as subcutaneous injection up to 48 weeks.; Drug: Placebo for JNJ-56136379; Matching placebo for JNJ-56136379 tablets will be administered orally up to 48 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance at Week 72 (24 weeks after completion of all study interventions at Week 48) Without Restarting NA Treatment	Percentage of participants with HBsAg seroclearance at week 72 (24 weeks after completion of all study interventions at Week 48) without restarting nucleos(t)ide analog (NA) treatment will be reported.	Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of JNJ-73763989	The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.	Days 1, 29, 85, 169 and 337
Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of JNJ-56136379	The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.	Days 1, 29, 85, 169 and 337
Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of NA	The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.	Days 1, 29, 85, 169 and 337
Number of Participants with Adverse Events (AEs) and Serious AEs	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Up to 102 weeks
Number of Participants with Abnormalities in Clinical Laboratory Tests	Number of participants with abnormalities in clinically significant laboratory findings (urine chemistry and renal biomarkers) will be reported.	Up to 102 weeks
Percentage of Participants with HBsAg Seroclearance at Week 48	Percentage of participants with HBsAg seroclearance at week 48 will be reported.	Week 48
Percentage of Participants with HBV DNA less than (<) Lower Limit of Quantification (LLOQ) at Week 48	Percentage of participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <LLOQ at week 48 will be reported.	Week 48
Percentage of Participants with HBsAg Seroclearance at Week 96 (48 Weeks After Completion of all Study Intervention) Without Restarting NA Treatment	Percentage of participants with HBsAg seroclearance up to week 96 (48 weeks after completion of all study intervention) without restarting NA treatment will be reported.	Up to Week 96
Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance	Percentage of participants with (sustained) reduction, suppression, and/or seroclearance considering single and multiple markers (such as hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], HBV DNA and alanine aminotransferase [ALT]) will be reported.	Up to Week 96
Time to Achieve First HBsAg Seroclearance	Time to achieve first HBsAg seroclearance will be reported.	Up to Week 96
Percentage of participants with HBV DNA levels with <LLOQ	Percentage of participants with HBV DNA levels with lower limit of quantification (<LLOQ) assay will be reported.	Up to Week 96
Percentage of Participants with Virologic Breakthrough	Percentage of participants with virologic breakthrough defined as confirmed on-treatment HBV DNA increase by greater than (>)1 log10 IU/mL from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below <LLOQ of the HBV DNA assay will be reported.	Up to Week 48
Percentage of Participants with Flares	Percentage of participants with flares (virologic, biochemical and clinical flares) will be reported.	Up to week 96
Percentage of Participants Requiring NA Re-Treatment During Follow-up	Percentage of participants requiring NA re-treatment during follow-up will be reported.	Up to week 96
Association Between Baseline Characteristics and On-Treatment Viral Blood Markers with Selected Off-Treatment Responses	Identification of baseline characteristics and on treatment viral blood markers (e.g., HBV DNA, HBsAg, ALT) associated with sustained off-treatment responses will be reported.	Baseline to week 72

Collaborators and Investigators

• Sponsor: Janssen Sciences Ireland UC
• Investigators: Study Director: Janssen Sciences Ireland UC Clinical Trial, Janssen Sciences Ireland UC

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2019
• Primary Completion (Actual): July 8, 2021
• Study Completion (Actual): June 9, 2022

Study Registration Dates

• First Submitted: October 15, 2019
• First Submitted That Met QC Criteria: October 15, 2019
• First Posted (Actual): October 17, 2019

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 30, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Virus Diseases; Hepatitis B, Chronic; Herpesviridae Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Entecavir; JNJ-56136379
• Other Study ID Numbers: CR108679; 73763989PAHPB2002 (Other Identifier: Janssen Sciences Ireland UC); 2019-002674-31 (EudraCT Number)

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