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

NCT ID: NCT03361956

Last Updated: 2022-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 232 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-13
• Study Completion Date: 2020-08-13

Brief Summary

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.

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.

Conditions

Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

JNJ-56136379

Intervention Type: DRUG

Participants will receive JNJ-56136379 tablet orally.

NA (ETV or TDF)

Intervention Type: DRUG

Participants will receive NA (ETV or TDF) tablet orally as per approved label.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive matching placebo tablet orally.

NA (ETV or TDF)

Intervention Type: DRUG

Participants will receive NA (ETV or TDF) tablet orally as per approved label.

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.

Group Type: EXPERIMENTAL

JNJ-56136379

Intervention Type: DRUG

Participants will receive JNJ-56136379 tablet orally.

NA (ETV or TDF)

Intervention Type: DRUG

Participants will receive NA (ETV or TDF) tablet orally as per approved label.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive matching placebo tablet orally.

NA (ETV or TDF)

Intervention Type: DRUG

Participants will receive NA (ETV or TDF) tablet orally as per approved label.

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.

Group Type: EXPERIMENTAL

JNJ-56136379

Intervention Type: DRUG

Participants will receive JNJ-56136379 tablet orally.

NA (ETV or TDF)

Intervention Type: DRUG

Participants will receive NA (ETV or TDF) tablet orally as per approved label.

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.

Group Type: EXPERIMENTAL

JNJ-56136379

Intervention Type: DRUG

Participants will receive JNJ-56136379 tablet orally.

NA (ETV or TDF)

Intervention Type: DRUG

Participants will receive NA (ETV or TDF) tablet orally as per approved label.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive matching placebo tablet orally.

NA (ETV or TDF)

Intervention Type: DRUG

Participants will receive NA (ETV or TDF) tablet orally as per approved label.

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.

Group Type: EXPERIMENTAL

JNJ-56136379

Intervention Type: DRUG

Participants will receive JNJ-56136379 tablet orally.

NA (ETV or TDF)

Intervention Type: DRUG

Participants will receive NA (ETV or TDF) tablet orally as per approved label.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive matching placebo tablet orally.

NA (ETV or TDF)

Intervention Type: DRUG

Participants will receive NA (ETV or TDF) tablet orally as per approved label.

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.

Group Type: EXPERIMENTAL

JNJ-56136379

Intervention Type: DRUG

Participants will receive JNJ-56136379 tablet orally.

NA (ETV or TDF)

Intervention Type: DRUG

Participants will receive NA (ETV or TDF) tablet orally as per approved label.

Interventions

JNJ-56136379

Participants will receive JNJ-56136379 tablet orally.

Intervention Type: DRUG

Placebo

Participants will receive matching placebo tablet orally.

Intervention Type: DRUG

NA (ETV or TDF)

Participants will receive NA (ETV or TDF) tablet orally as per approved label.

Intervention Type: DRUG

Other Intervention Names

JNJ-6379

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Sciences Ireland UC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Sciences Ireland UC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Sciences Ireland UC

Locations

The Office of Franco Felizarta, MD

Bakersfield, California, United States

Orlando Immunology Center

Orlando, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Tulane Medical Center (TMC)

New Orleans, Louisiana, United States

I.D. Care, Inc.

Hillsborough, New Jersey, United States

NYU Hepatology Associates

New York, New York, United States

UPMC Center For Liver Diseases

Pittsburgh, Pennsylvania, United States

SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)

Antwerp, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

UZ Antwerpen

Edegem, , Belgium

University of Calgary

Calgary, Alberta, Canada

Vancouver ID Research and Care Centre Society

Vancouver, British Columbia, Canada

GI Research Institute (G.I.R.I.)

Vancouver, British Columbia, Canada

McGill University Health Centre

Montreal, Quebec, Canada

Toronto General Hospital

Toronto, , Canada

Peking University People's Hospital

Beijing, , China

Beiijing Friendship Hospital, Capital Medical University

Beijing, , China

The First Hospital of Jilin University

Changchun, , China

Nanfang Hospital

Guangzhou, , China

Hôpital Beaujon

Clichy, , France

Hopital de La Croix Rousse

Lyon, , France

Hopital Saint-Antoine

Paris, , France

Hopital Paul Brousse

Villejuif, , France

Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH

Berlin, , Germany

Universitatsklinikum Essen

Essen, , Germany

Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1

Frankfurt, , Germany

Asklepios Klinik St. Georg, Haus Lifi - Studien und Projekte GmbH

Hamburg, , Germany

Queen Mary Hospital, University of Hong Kong

Hong Kong, , Hong Kong

The Chinese University of Hong Kong

Shatin, , Hong Kong

Irccs Ospedale Maggiore Di Milano

Milan, , Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Hiroshima University Hospital

Hiroshima, , Japan

Musashino Red Cross Hospital

Musashino, , Japan

National Hospital Organization Nagasaki Medical Center

Nagasaki, , Japan

Nagoya City University Hospital

Nagoya, , Japan

Osaka University Hospital

Suita-shi, , Japan

Hospital Sultanah Bahiyah

Alor Star, , Malaysia

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Szpital Specjalistyczny w Chorzowie

Chorzów, , Poland

Wojewodzki Szpital Zespolony

Kielce, , Poland

ID Clinic

Mysłowice, , Poland

SP ZOZ Wroclawskie Centrum Zdrowia

Wroclaw, , Poland

Medical Center SibNovoMed LLC

Novosibirsk, , Russia

Medical Company Hepatolog Ltd

Samara, , Russia

Stavropol State Medical University

Stavropol, , Russia

Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, , Russia

Pusan National University Hospital

Busan, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Hosp. Clinic I Provincial de Barcelona

Barcelona, , Spain

Hosp. Univ. Vall D Hebron

Barcelona, , Spain

Hosp. Univ. Ramon Y Cajal

Madrid, , Spain

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

Hosp. Virgen Del Rocio

Seville, , Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

Chang Gung Memorial Hospital Linkou Branch

Taoyuan District, , Taiwan

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Siriraj Hospital

Bangkok, , Thailand

Chiang Mai University Hospital

Chiang Mai, , Thailand

Prince Of Songkla University

Songkhla, , Thailand

Istanbul University Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Saglık Bilimleri University Şişli Trainig and Research Hospital,Department of Gastroenterology

Istanbul, , Turkey (Türkiye)

Ege University Medical of Faculty, Department of Gastroenterology

Izmir, , Turkey (Türkiye)

Karadeniz Teknik University Medical Faculty

Trabzon, , Turkey (Türkiye)

Kharkiv National Medical University, Regional Clinical Infectious Hospital

Kharkiv, , Ukraine

SE 'National institute therapy named L.T. Maloi NAMS of Ukraine'

Kharkiv, , Ukraine

Odessa Regional Clinical Hospital

Odesa, , Ukraine

Vinnytsia City Clinical Hospital #1, Department of Infectious Diseases #1

Vinnytsia, , Ukraine

North Manchester General Hospital

Crumpsall, , United Kingdom

Grahame Hayton Unit

London, , United Kingdom

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Countries

United States; Belgium; Canada; China; France; Germany; Hong Kong; Italy; Japan; Malaysia; Poland; Russia; South Korea; Spain; Taiwan; Thailand; Turkey (Türkiye); Ukraine; United Kingdom

References

Verbinnen T, Talloen W, Janssen HLA, Zoulim F, Shukla U, Vandenbossche JJ, Biermer M, De Meyer S, Lenz O. Viral sequence analysis of chronic hepatitis B patients treated with the capsid assembly modulator JNJ-56136379 in the JADE phase 2a study. Antiviral Res. 2023 Aug;216:105660. doi: 10.1016/j.antiviral.2023.105660. Epub 2023 Jun 28.

Reference Type: DERIVED

PMID: 37385475 (View on PubMed)

Janssen HLA, Hou J, Asselah T, Chan HLY, Zoulim F, Tanaka Y, Janczewska E, Nahass RG, Bourgeois S, Buti M, Lampertico P, Lenz O, Verbinnen T, Vandenbossche J, Talloen W, Kalmeijer R, Beumont M, Biermer M, Shukla U. Randomised phase 2 study (JADE) of the HBV capsid assembly modulator JNJ-56136379 with or without a nucleos(t)ide analogue in patients with chronic hepatitis B infection. Gut. 2023 Jul;72(7):1385-1398. doi: 10.1136/gutjnl-2022-328041. Epub 2023 Jan 25.

Reference Type: DERIVED

PMID: 36697207 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32094138 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-001110-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

56136379HPB2001

Identifier Type: OTHER

Identifier Source: secondary_id

CR108410

Identifier Type: -

Identifier Source: org_study_id