An Efficacy, Safety, and Pharmacokinetics Study of JNJ-56136379 in Participants With Chronic Hepatitis B Virus Infection

A Phase 2a, Randomized, Partially-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Pharmacokinetics of Treatment With Multiple Doses of JNJ-56136379 as Monotherapy and in Combination With a Nucleos(t)Ide Analog in Subjects With Chronic Hepatitis B Virus Infection

The main purpose of this study is to evaluate efficacy of 24 weeks of study treatment, in terms of changes in hepatitis B surface antigen (HBsAg) levels.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Drug: JNJ-56136379; Drug: NA (ETV or TDF); Drug: Placebo

Detailed Description

The main study consists of 2-parts and each part will consist of 2 types of Chronic Hepatitis B-infected participant populations. Each part of the study will consist of screening phase (up to 8 weeks), treatment phase (24 weeks or 48 weeks, depending on treatment response), and post-treatment follow-up phase (24 weeks or 48 weeks, depending on treatment response). The duration of individual participation will be up to approximately 56 weeks (participants not eligible to continue treatment in extension phase), up to 80 weeks (participants continuing treatment in extension phase but not meeting treatment completion criteria), or up to 104 weeks (participants meeting treatment completion criteria). The safety and efficacy will be monitored throughout the study. In a separate substudy, at selected clinical sites, percutaneous core liver biopsy will be performed to evaluate changes of intrahepatic viral parameters.

• Study Type: Interventional
• Enrollment (Actual): 232
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Edegem, Belgium, 2650
    • UZ Antwerpen
• Canada
  • Toronto, Canada, ON M5G 2C4
    • Toronto General Hospital
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • University of Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • GI Research Institute (G.I.R.I.)
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • Vancouver ID Research and Care Centre Society
  • Quebec
    • Montreal, Quebec, Canada, H3H 2R9
      • McGill University Health Centre
• China
  • Beijing, China, 100034
    • Peking University People's Hospital
  • Beijing, China, 100050
    • Beiijing Friendship Hospital, Capital Medical University
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Guangzhou, China, 510515
    • Nanfang Hospital
• France
  • Clichy, France, 92110
    • Hôpital Beaujon
  • Lyon, France, 69004
    • Hopital de la croix rousse
  • Paris, France, 75012
    • Hopital Saint-Antoine
  • Villejuif, France, 94800
    • Hôpital Paul Brousse
• Germany
  • Berlin, Germany, 10439
    • Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
  • Essen, Germany, 45122
    • Universitätsklinikum Essen
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
  • Hamburg, Germany, 20099
    • Asklepios Klinik St. Georg, Haus Lifi - Studien und Projekte GmbH
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital, University of Hong Kong
  • Shatin, Hong Kong
    • The Chinese University of Hong Kong
• Italy
  • Milano, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Milano, Italy, 20122
    • Irccs Ospedale Maggiore Di Milano
  • Pisa, Italy, 56124
    • Azienda Ospedaliero Universitaria Pisana
• Japan
  • Hiroshima-shi, Japan, 734-8551
    • Hiroshima University Hospital
  • Musashino, Japan, 180-8610
    • Musashino Red Cross Hospital
  • Nagasaki, Japan, 856-8562
    • National Hospital Organization Nagasaki Medical Center
  • Nagoya, Japan, 467-8602
    • Nagoya City University Hospital
  • Suita-shi, Japan, 565-0871
    • Osaka University Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
• Malaysia
  • Alor Setar, Malaysia, 05460
    • Hospital Sultanah Bahiyah
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre
• Poland
  • Chorzow, Poland, 41-500
    • Szpital Specjalistyczny w Chorzowie
  • Kielce, Poland, 25-317
    • Wojewodzki Szpital Zespolony
  • Myslowice, Poland, 41-400
    • ID Clinic
  • Wroclaw, Poland, 50-136
    • SP ZOZ Wroclawskie Centrum Zdrowia
• Russian Federation
  • Ekaterinburg, Russian Federation, 620102
    • Sverdlovsk Regional Clinical Hospital #1
  • Novosibirsk, Russian Federation, 630005
    • Medical Center SibNovoMed LLC
  • Samara, Russian Federation, 443063
    • Medical Company Hepatolog Ltd
  • Stavropol, Russian Federation, 355017
    • Stavropol State Medical University
• Spain
  • Barcelona, Spain, 8035
    • Hosp. Univ. Vall D Hebron
  • Barcelona, Spain, 8028
    • Hosp. Clinic I Provincial de Barcelona
  • Madrid, Spain, 28034
    • Hosp. Univ. Ramon Y Cajal
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
  • Sevilla, Spain, 41013
    • Hosp. Virgen Del Rocio
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Tao-Yuan, Taiwan, 333
    • Chang Gung Memorial Hospital Linkou Branch
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand, 10500
    • King Chulalongkorn Memorial Hospital
  • Chiang Mai, Thailand, 50200
    • Chiang Mai University Hospital
  • Songkla, Thailand, 90110
    • Prince of Songkla University
• Turkey
  • Istanbul, Turkey, 34098
    • Istanbul University Cerrahpasa Medical Faculty
  • Izmir, Turkey, 35100
    • Ege University Medical of Faculty, Department of Gastroenterology
  • Trabzon, Turkey, 61080
    • Karadeniz Teknik University Medical Faculty
  • İstanbul, Turkey, 34371
    • Saglık Bilimleri University Şişli Trainig and Research Hospital,Department of Gastroenterology
• Ukraine
  • Kharkiv, Ukraine, 61000
    • Kharkiv National Medical University, Regional Clinical Infectious Hospital
  • Kharkiv, Ukraine, 61039
    • SE 'National institute therapy named L.T. Maloi NAMS of Ukraine'
  • Odessa, Ukraine, 65025
    • Odessa regional clinical Hospital
  • Vinnytsya, Ukraine, 21021
    • Vinnytsia City Clinical Hospital #1, Department of Infectious Diseases #1
• United Kingdom
  • Crumpsall, United Kingdom, M8 5RB
    • North Manchester General Hospital
  • London, United Kingdom, E1 1BB
    • Grahame Hayton Unit
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospitals NHS Trust
• United States
  • California
    • Bakersfield, California, United States, 93301
      • The Office of Franco Felizarta, MD
  • Florida
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center (TMC)
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • I.D. Care, Inc.
  • New York
    • New York, New York, United States, 10016
      • NYU Hepatology Associates
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Center for Liver Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must have a body mass index (weight in kilogram (kg) divided by the square of height in meters) of 18.0 to 35.0 kilogram / square meter (kg/m^2), extremes included
• Participants must have chronic hepatitis B virus infection (CHB) infection documented by: Serum hepatitis B surface antigen (HBsAg)-positive at screening and serum HBsAg- or hepatitis B virus (HBV) deoxyribonucleic acid (DNA)-positive at least 6 months prior to screening; Serum immunoglobulin M (IgM) anti- hepatitis B core-related (HBc) antibody negative at screening
• In participants currently not being treated (Treatment Arms 1-2-3 and 6-7-8): Participants must not be receiving any CHB treatment at screening, that is, Have never received treatment with HBV antiviral medicines, including NAs or interferon (IFN) products, OR Have not been on treatment with HBV antiviral medicines, including nucleos(t)ide analog (NA)s or IFN products within 6 months prior to baseline (first intake of study drugs), and participants must be HBeAg-positive and have HBV DNA greater than or equal to (>=) 20,000 International Units Per Milliliter (IU/mL), OR be hepatitis B e antigen (HBeAg)-negative and have HBV DNA >=2,000 IU /mL at screening, and participants must have HBsAg greater than (>) 250 IU/mL at screening, and participants must have alanine aminotransferase (ALT) > upper limit of normal (ULN) and less than or equal to (<=) 5 * ULN at screening, determined in the central laboratory
• In virologically suppressed participants (Treatment Arms 4-5 and 9-10): Participants must be virologically suppressed by current NA treatment (entecavir (ETV) or tenofovir disoproxil fumarate (TDF)) as defined by HBV DNA less than (<) 60 IU/mL at screening and at least 6 months prior to screening, and participants must be on the same NA treatment (ETV or TDF) and the same dose for >=12 months prior to screening, and participants must have HBsAg > 250 IU/mL at screening, and participants must have ALT <=2*ULN at screening
• Participants must have: A liver biopsy result classified as Metavir F0-F2 within 1 year prior to screening or at the time of screening, OR FibroScan liver stiffness measurement <8.0 kilopascal (kPa) within 6 months prior to screening or at the time of screening

Exclusion Criteria:

Main Study:

• Participants who test positive for anti-hepatitis B surface (HBs) antibodies
• Participants with current hepatitis A virus infection (confirmed by hepatitis A antibody immunoglobulin M [IgM]), hepatitis D virus (HDV) infection (confirmed by HDV antibody), hepatitis E virus infection (confirmed by hepatitis E antibody IgM), or human immunodeficiency virus (HIV)-1 or HIV-2 infection (confirmed by antibodies) at screening; participants with a history of or current HCV infection (confirmed by HCV antibody). Evidence of other active infection (bacterial, viral, fungal, including acute tuberculosis) deemed clinically relevant by the investigator that would interfere with study conduct or its interpretation will also lead to exclusion
• Participants with any evidence of hepatic decompensation at any time point prior to or at the time of screening: Direct bilirubin >1.2* ULN, or International normalized ratio (INR) >1.5* ULN, or Serum albumin < lower limit of normal (LLN), or documented history or current evidence of variceal bleeding, ascites, or hepatic encephalopathy
• Participants with a history of cardiac arrhythmia (example, extrasystoli, tachycardia at rest), history of risk factors for Torsades de Pointes syndrome (example, hypokalemia, family history of long QT syndrome) or history or other clinical evidence of significant or unstable cardiac disease (example, angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease, and/or clinically significant 12 lead electrocardiograms (ECGs) abnormalities), moderate to severe valvular disease, or uncontrolled hypertension at screening
• Participants with contraindications to the use of ETV or TDF per local prescribing information

Substudy:

• Presence of coagulopathy or hemoglobinopathy (including sickle cell disease, thalassemia)
• Use of any anti-coagulant, anti-platelet, or non-steroidal anti-inflammatory drug medications from 10 days before until 5 days after each liver biopsy
• Presence of ascites, focal liver lesions, and other findings that would be contraindications for liver biopsies

Study Plan

How is the study designed?

Design Details

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

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Arm 1 (JNJ-56136379 or NA) (open label); Participants with hepatitis B virus (HBV) currently not being treated and receiving JNJ-56136379 tablet (at a lower dose) orally for 24 weeks, will stop further dosing with JNJ-56136379 and start treatment with nucleos(t)ide analog (NA) (entecavir [ETV] or tenofovir disoproxil fumarate [TDF]), and enter the 24 week post treatment follow-up phase.	Drug: JNJ-56136379; Participants will receive JNJ-56136379 tablet orally.; Other Names: JNJ-6379; Drug: NA (ETV or TDF); Participants will receive NA (ETV or TDF) tablet orally as per approved label.
Placebo Comparator: Part A: Arm 2 (Placebo+NA [ETV] or [TDF]); Participants with HBV currently not being treated will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.	Drug: NA (ETV or TDF); Participants will receive NA (ETV or TDF) tablet orally as per approved label.; Drug: Placebo; Participants will receive matching placebo tablet orally.
Experimental: Part A: Arm 3 (JNJ-56136379 + NA [ETV or TDF]); Participants with HBV currently not being treated will receive JNJ-56136379 along with NA (ETV or TDF) tablet orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.	Drug: JNJ-56136379; Participants will receive JNJ-56136379 tablet orally.; Other Names: JNJ-6379; Drug: NA (ETV or TDF); Participants will receive NA (ETV or TDF) tablet orally as per approved label.
Placebo Comparator: Part A: Arm 4 (Placebo + NA [ETV or TDF]); Virologically suppressed participants will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.	Drug: NA (ETV or TDF); Participants will receive NA (ETV or TDF) tablet orally as per approved label.; Drug: Placebo; Participants will receive matching placebo tablet orally.
Experimental: Part A: Arm 5 (JNJ-56136379 + NA [ETV or TDF]); Virologically suppressed participants will receive JNJ-56136379 along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.	Drug: JNJ-56136379; Participants will receive JNJ-56136379 tablet orally.; Other Names: JNJ-6379; Drug: NA (ETV or TDF); Participants will receive NA (ETV or TDF) tablet orally as per approved label.
Experimental: Part B: Arm 6 (JNJ-56136379 + NA [ETV or TDF]) (open label); Participants with HBV currently not being treated will receive JNJ-56136379 tablet at a high dose, orally for 24 weeks. The eligible participants may enter the extension phase and will receive JNJ-56136379 along with NA (ETV or TDF) from Week 24 to Week 48.	Drug: JNJ-56136379; Participants will receive JNJ-56136379 tablet orally.; Other Names: JNJ-6379; Drug: NA (ETV or TDF); Participants will receive NA (ETV or TDF) tablet orally as per approved label.
Placebo Comparator: Part B: Arm 7 (placebo + NA [ETV or TDF]); Participants with HBV currently not being treated will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.	Drug: NA (ETV or TDF); Participants will receive NA (ETV or TDF) tablet orally as per approved label.; Drug: Placebo; Participants will receive matching placebo tablet orally.
Experimental: Part B: Arm 8 (JNJ-56136379 + NA [ETV or TDF]); Participants with HBV currently not being treated will receive JNJ-56136379 tablet at a high dose along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.	Drug: JNJ-56136379; Participants will receive JNJ-56136379 tablet orally.; Other Names: JNJ-6379; Drug: NA (ETV or TDF); Participants will receive NA (ETV or TDF) tablet orally as per approved label.
Placebo Comparator: Part B: Arm 9 (placebo + NA [ETV or TDF]); Virologically suppressed participants will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.	Drug: NA (ETV or TDF); Participants will receive NA (ETV or TDF) tablet orally as per approved label.; Drug: Placebo; Participants will receive matching placebo tablet orally.
Experimental: Part B: Arm 10 (JNJ-56136379 + NA [ETV or TDF]); Virologically suppressed participants will receive JNJ-56136379 tablet at a high dose along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.	Drug: JNJ-56136379; Participants will receive JNJ-56136379 tablet orally.; Other Names: JNJ-6379; Drug: NA (ETV or TDF); Participants will receive NA (ETV or TDF) tablet orally as per approved label.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels in Currently Not Treated Population at Week 24	Change from baseline in HBsAg levels in currently not treated population at Week 24 based on Hepatitis B e Antigen (HBeAg) status was reported. Currently not treated population defined as participants who didn't receive any hepatitis B virus (HBV) treatment 6 months prior to baseline.	Baseline and Week 24
Change From Baseline in HBsAg Levels in Virologically Suppressed Population at Week 24	Change from baseline in HBsAg levels in virologically suppressed population at Week 24 based on HBeAg status was reported. Virologically suppressed population defined as participants who were on entecavir (ETV) or tenofovir disoproxil fumarate (TDF) for at least 12 months prior to screening and had HBV deoxyribonucleic acid (DNA) <60 IU/mL. This outcome measure was planned to be analyzed for specified arms only.	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment- Emergent Adverse Events (AEs)	An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Treatment-emergent AEs were AEs with onset during the treatment phase or that worsened since baseline.	Up to Week 48
Number of Participants With Serious Adverse Events (SAEs)	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 Week 80
Number of Participants With Clinically Significant Changes in Vital Signs, Physical Examinations, Electrocardiogram (ECG), and Clinical Laboratory Tests	Number of participants with clinically significant changes in vital signs, physical examinations, ECG, and clinical laboratory tests (including hematology, blood biochemistry, blood coagulation, and urinalysis) were reported.	Up to Week 80
Change From Baseline in HBsAg Levels in Currently Not Treated Population Over Time	Change from baseline in HBsAg levels in currently not treated population based on HBeAg status was reported.	Weeks 24, 48 and Follow-up Week 24
Change From Baseline in HBsAg Levels in Virologically Suppressed Population Over Time	Change from baseline in HBsAg levels in virologically suppressed population based on HBeAg status was reported. This outcome measure was planned to be analyzed for specified arms only.	Weeks 24, 48 and Follow-up Week 24
Percentage of Participants With HBsAg Levels Less Than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) in Currently Not Treated Population	Percentage of participants with HBsAg levels <1,000 or <100 IU/mL in currently not treated population based on their HBeAg status were reported.	Weeks 24, 48 and Follow-up Week 24
Percentage of Participants With HBsAg Levels <1,000 or <100 IU/mL in Virologically Suppressed Population	Percentage of participants with HBsAg levels <1,000 or <100 IU/mL in virologically suppressed population based on their HBeAg status were reported. This outcome measure was planned to be analyzed for specified arms only.	Weeks 24, 48 and Follow-up Week 24
Percentage of Participants With Greater Than (>) 0.5 log10 IU/mL or >1 log10 IU/mL Reduction in HBsAg From Baseline in Currently Not Treated Population	Percentage of participants with >0.5 log10 IU/mL or >1 log10 IU/mL reduction in HBsAg from baseline in currently not treated population based on their HBeAg status were reported.	Weeks 24, 48 and Follow-up Week 24
Percentage of Participants With >0.5 log10 IU/mL or >1 log10 IU/mL Reduction in HBsAg From Baseline in Virologically Suppressed Population	Percentage of participants with >0.5 log10 IU/mL or >1 log10 IU/mL reduction in HBsAg from baseline in virologically suppressed population based on their HBeAg status were reported. This outcome measure was planned to be analyzed for specified arms only.	Weeks 24, 48 and Follow-up Week 24
Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels in Currently Not Treated Population	Change from baseline in HBV DNA levels in currently not treated population based on their HBeAg status was reported.	Baseline up to Weeks 24, 48 and Follow-up Week 24
Change From Baseline in HBV DNA Levels in Virologically Suppressed Population	Change from baseline in HBV DNA levels in virologically supressed population based on their HBeAg status was reported. This outcome measure was planned to be analyzed for specified arms only.	Baseline up to Weeks 24, 48 and Follow-up Week 24
Percentage of Participants With Undetectable HBV DNA Levels in Currently Not Treated Population	Percentage of participants with undetectable HBV DNA levels in currently not treated population based on their HBeAg status was evaluated.	Weeks 24, 48 and Follow-up Week 24
Percentage of Participants With Undetectable HBV DNA Levels in Virologically Suppressed Population	Percentage of participants with undetectable HBV DNA levels in virologically suppressed population based on their HBeAg status were reported. This outcome measure was planned to be analyzed for specified arms only.	Weeks 24, 48 and Follow-up Week 24
Change From Baseline in HBeAg Levels in Currently Not Treated Population	Change from baseline in HBeAg levels in HBeAg positive currently not treated population was reported.	Baseline up to Weeks 24, 48 and Follow-up Week 24
Change From Baseline in HBeAg Levels in Virologically Suppressed Population	Change from baseline in HBeAg levels in HBeAg positive virologically suppressed population was reported. This outcome measure was planned to be analyzed for specified arms only.	Baseline up to Weeks 24, 48 and Follow-up Week 24
Percentage of Participants With >0.5 log10 IU/mL and >1 log10 IU/mL Reduction in HBeAg From Baseline in Currently Not Treated Population	Percentage of participants with >0.5 log10 IU/mL and >1 log10 IU/mL reduction in HBeAg from baseline in HBeAg positive currently not treated population was reported.	Weeks 24, 48 and Follow-up Week 24
Percentage of Participants With >0.5 log10 IU/mL and >1 log10 IU/mL Reduction in HBeAg From Baseline in Virologically Suppressed Population	Percentage of participants with >0.5 log10 IU/mL and >1 log10 IU/mL reduction in HBeAg from baseline in HBeAg positive virologically suppressed population was reported. This outcome measure was planned to be analyzed for specified arms only.	Weeks 24, 48 and Follow-up Week 24
Percentage of Participants With HBsAg Seroclearance in Currently Not Treated Population	Percentage of participants with HBsAg seroclearance in currently not treated population based on their HBeAg status were reported. Seroclearance at Week 24/48 of the treatment defined as a confirmed loss of HBsAg at Week 24/48. Loss is defined as a baseline HBsAg with a repeat reactive, confirmed or positive result and a post-baseline assessment with a negative result. This outcome measure was planned to be analyzed at specified timepoints only.	Weeks 24 and 48
Percentage of Participants With HBsAg Seroclearance in Virologically Suppressed Population	Percentage of participants with HBsAg seroclearance in virologically suppressed population based on their HBeAg status were reported. Seroclearance at Week 24/48 of the treatment defined as a confirmed loss of HBsAg at Week 24/48. Loss is defined as a baseline HBsAg with a repeat reactive, confirmed or positive result and a post-baseline assessment with a negative result. This outcome measure was planned to be analyzed for specified arms and specific timepoints only .	Weeks 24 and 48
Percentage of Participants With HBsAg Seroconversion in Currently Not Treated Population	Percentage of participants with HBsAg seroconversion in currently not treated population based on their HBeAg status were reported. Seroconversion at Week 24/48 of the treatment defined as a confirmed loss of HBsAg at week 24/48 of the treatment and an appearance of Anti-HBs. This outcome measure was planned to be analyzed for specified timepoints only.	Weeks 24 and 48
Percentage of Participants With HBsAg Seroconversion in Virologically Suppressed Population	Percentage of participants with HBsAg seroconversion in virologically suppressed population based on their HBeAg status were reported. Seroconversion at Week 24/48 of the treatment defined as a confirmed loss of HBsAg at week 24/48 of the treatment and an appearance of Anti-HBs. This outcome measure was planned to be analyzed for specified arms and specified timepoints only.	Weeks 24 and 48
Percentage of Participants With Normalized Alanine Aminotransferase (ALT) Levels in Currently Not Treated Population	Percentage of participants with normalized ALT levels in currently not treated population, whose ALT levels were above upper limit of normal at baseline based on their HBeAg status were reported.	Weeks 24, 48 and Follow-up Week 24
Percentage of Participants With Normalized ALT Levels in Virologically Suppressed Population	Percentage of participants with normalized ALT levels in virologically suppressed population, whose ALT levels were above upper limit of normal at baseline based on their HBeAg status were reported. This outcome measure was planned to be analyzed for specified arms only.	Weeks 24, 48 and Follow-up Week 24
Percentage of Participants With Virological Breakthrough in Currently Not Treated Population	Percentage of participants with virological breakthrough in currently not treated population based on their HBeAg status was reported. Virological breakthrough defined as confirmed on treatment HBV DNA increase by >1 log10 from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below the lower limit of quantification (LLOQ) of the HBV DNA assay.	Weeks 24 and 48
Percentage of Participants With Virological Breakthrough in Virologically Suppressed Population	Percentage of participants with virological breakthrough in virologically suppressed population based on their HBeAg status was reported. Virological breakthrough defined as confirmed on treatment HBV DNA increase by >1 log10 from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below the lower limit of quantification (LLOQ) of the HBV DNA assay. This outcome measure was planned to be analyzed for specified arms only.	Weeks 24 and 48
Plasma Concentrations of Entecavir [ETV] in Currently Not Treated Population	Plasma concentrations of ETV administered as monotherapy or co-administered with JNJ-56136379 in currently not treated population was determined. As planned, plasma concentration of ETV co-administered with placebo was analyzed separately for Part A and Part B. Samples were analyzed using POP PK modeling.	Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4
Plasma Concentrations of ETV in Virologically Suppressed Population	Plasma concentrations of ETV administered as monotherapy or co-administered with JNJ-56136379 in virologically suppressed population was determined. As planned, plasma concentration of ETV co-administered with placebo was analyzed separately for Part A and Part B. Samples were analyzed using POP PK modeling.	Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4
Plasma Concentrations of Tenofovir Disoproxil Fumarate (TDF) in Currently Not Treated Population	Plasma concentrations of TDF administered as monotherapy or co-administered with JNJ-56136379 was determined. As planned, plasma concentration of TDF co-administered with placebo was analyzed separately for Part A and Part B. Samples were analyzed using POP PK modeling.	Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4
Plasma Concentrations of TDF in Virologically Suppressed Population	Plasma concentrations of TDF administered as monotherapy or co-administered with JNJ-56136379 was determined. As planned, plasma concentration of TDF co-administered with placebo was analyzed separately for Part A and Part B. Samples were analyzed using POP PK modeling.	Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4
Plasma Concentrations of JNJ-56136379 in Currently Not Treated Population	Plasma concentrations of JNJ-56136379 in currently not treated population administered as monotherapy or when co-administered with NA (ETV or TDF) was determined. As planned, the plasma concentration of JNJ-56136379 when co-administered with NA was determined separately for each NA treatment (ETV and TDF). Samples were analyzed using POP PK modeling.	Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4
Plasma Concentrations of JNJ-56136379 in Virologically Suppressed Population	Plasma concentrations of JNJ-56136379 in virologically suppressed population administered as monotherapy or when co-administered with NA (ETV or TDF) was determined. As planned, the plasma concentration of JNJ-56136379 when co-administered with NA was determined separately for each NA treatment (ETV and TDF). Samples were analyzed using POP PK modeling.	Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4
Number of Participants With Treatment-Associated Mutations	Number of participants with treatment-associated mutations were reported. Viral genome sequence analysis was performed to evaluate emergence of mutations associated with JNJ-56136379 considering 15 HBV core protein positions of interest. This outcome measure was planned to be analyzed for specified arms only.	From Week 0 to Week 24, From Week 25 to Week 48, Up to Follow-up Week 24

Collaborators and Investigators

• Sponsor: Janssen Sciences Ireland UC

Publications and helpful links

General Publications

• Berke JM, Dehertogh P, Vergauwen K, Mostmans W, Vandyck K, Raboisson P, Pauwels F. Antiviral Properties and Mechanism of Action Studies of the Hepatitis B Virus Capsid Assembly Modulator JNJ-56136379. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02439-19. doi: 10.1128/AAC.02439-19. Print 2020 Apr 21.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2018
• Primary Completion (Actual): September 5, 2019
• Study Completion (Actual): August 13, 2020

Study Registration Dates

• First Submitted: November 29, 2017
• First Submitted That Met QC Criteria: November 29, 2017
• First Posted (Actual): December 5, 2017

Study Record Updates

• Last Update Posted (Actual): November 17, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Virus Diseases; Hepatitis B, Chronic; Herpesviridae Infections; Anti-Infective Agents; Antiviral Agents; JNJ-56136379
• Other Study ID Numbers: CR108410; 2017-001110-29 (EudraCT Number); 56136379HPB2001 (Other Identifier: Janssen Sciences Ireland UC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No