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

NCT03361956 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: CR1084102017-001110-2956136379HPB2001
• Study Type: interventional
• Target: 232
• Locations: 19 countries
• Sites: 76

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.

Conditions

Hepatitis B

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (32)

• Number of Participants With Treatment- Emergent Adverse Events (AEs)

  Up to Week 48

• Number of Participants With Serious Adverse Events (SAEs)

  Up to Week 80

• Number of Participants With Clinically Significant Changes in Vital Signs, Physical Examinations, Electrocardiogram (ECG), and Clinical Laboratory Tests

  Up to Week 80

• Change From Baseline in HBsAg Levels in Currently Not Treated Population Over Time

  Weeks 24, 48 and Follow-up Week 24

• Change From Baseline in HBsAg Levels in Virologically Suppressed Population Over Time

  Weeks 24, 48 and Follow-up Week 24

Study Arms (10)

Part A: Arm 1 (JNJ-56136379 or NA) (open label)

EXPERIMENTAL

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; Drug: NA (ETV or TDF)

Part A: Arm 2 (Placebo+NA [ETV] or [TDF])

PLACEBO COMPARATOR

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: Placebo; Drug: NA (ETV or TDF)

Part A: Arm 3 (JNJ-56136379 + NA [ETV or TDF])

EXPERIMENTAL

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; Drug: NA (ETV or TDF)

Part A: Arm 4 (Placebo + NA [ETV or TDF])

PLACEBO COMPARATOR

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: Placebo; Drug: NA (ETV or TDF)

Part A: Arm 5 (JNJ-56136379 + NA [ETV or TDF])

EXPERIMENTAL

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; Drug: NA (ETV or TDF)

Part B: Arm 6 (JNJ-56136379 + NA [ETV or TDF]) (open label)

EXPERIMENTAL

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; Drug: NA (ETV or TDF)

Part B: Arm 7 (placebo + NA [ETV or TDF])

PLACEBO COMPARATOR

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: Placebo; Drug: NA (ETV or TDF)

Part B: Arm 8 (JNJ-56136379 + NA [ETV or TDF])

EXPERIMENTAL

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; Drug: NA (ETV or TDF)

Part B: Arm 9 (placebo + NA [ETV or TDF])

PLACEBO COMPARATOR

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: Placebo; Drug: NA (ETV or TDF)

Part B: Arm 10 (JNJ-56136379 + NA [ETV or TDF])

EXPERIMENTAL

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; Drug: NA (ETV or TDF)

Interventions

JNJ-56136379 DRUG

Participants will receive JNJ-56136379 tablet orally.

Also known as: JNJ-6379

Part A: Arm 1 (JNJ-56136379 or NA) (open label); Part A: Arm 3 (JNJ-56136379 + NA [ETV or TDF]); Part A: Arm 5 (JNJ-56136379 + NA [ETV or TDF]); Part B: Arm 10 (JNJ-56136379 + NA [ETV or TDF]); Part B: Arm 6 (JNJ-56136379 + NA [ETV or TDF]) (open label); Part B: Arm 8 (JNJ-56136379 + NA [ETV or TDF])

Placebo DRUG

Participants will receive matching placebo tablet orally.

Part A: Arm 2 (Placebo+NA [ETV] or [TDF]); Part A: Arm 4 (Placebo + NA [ETV or TDF]); Part B: Arm 7 (placebo + NA [ETV or TDF]); Part B: Arm 9 (placebo + NA [ETV or TDF])

NA (ETV or TDF) DRUG

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

Part A: Arm 1 (JNJ-56136379 or NA) (open label); Part A: Arm 2 (Placebo+NA [ETV] or [TDF]); Part A: Arm 3 (JNJ-56136379 + NA [ETV or TDF]); Part A: Arm 4 (Placebo + NA [ETV or TDF]); Part A: Arm 5 (JNJ-56136379 + NA [ETV or TDF]); Part B: Arm 10 (JNJ-56136379 + NA [ETV or TDF]); Part B: Arm 6 (JNJ-56136379 + NA [ETV or TDF]) (open label); Part B: Arm 7 (placebo + NA [ETV or TDF]); Part B: Arm 8 (JNJ-56136379 + NA [ETV or TDF]); Part B: Arm 9 (placebo + NA [ETV or TDF])

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Main Study:
• Participants who test positive for anti-hepatitis B surface (HBs) antibodies
• 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

Sponsors & Collaborators

• Janssen Sciences Ireland UC: lead

Study Sites (76)

The Office of Franco Felizarta, MD

Bakersfield, California, 93301, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Tulane Medical Center (TMC)

New Orleans, Louisiana, 70112, United States

Location

I.D. Care, Inc.

Hillsborough, New Jersey, 08844, United States

Location

NYU Hepatology Associates

New York, New York, 10016, United States

Location

UPMC Center For Liver Diseases

Pittsburgh, Pennsylvania, 15213, United States

Location

SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)

Antwerp, 2060, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

Location

Vancouver ID Research and Care Centre Society

Vancouver, British Columbia, V6Z 2C7, Canada

Location

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

Vancouver, British Columbia, V6Z 2K5, Canada

Location

McGill University Health Centre

Montreal, Quebec, H3H 2R9, Canada

Location

Toronto General Hospital

Toronto, ON M5G 2C4, Canada

Location

Peking University People's Hospital

Beijing, 100034, China

Location

Beiijing Friendship Hospital, Capital Medical University

Beijing, 100050, China

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

Nanfang Hospital

Guangzhou, 510515, China

Location

Hôpital Beaujon

Clichy, 92110, France

Location

Hopital de La Croix Rousse

Lyon, 69004, France

Location

Hopital Saint-Antoine

Paris, 75012, France

Location

Hopital Paul Brousse

Villejuif, 94800, France

Location

Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH

Berlin, 10439, Germany

Location

Universitatsklinikum Essen

Essen, 45122, Germany

Location

Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1

Frankfurt, 60590, Germany

Location

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

Hamburg, 20099, Germany

Location

Queen Mary Hospital, University of Hong Kong

Hong Kong, Hong Kong

Location

The Chinese University of Hong Kong

Shatin, Hong Kong

Location

Irccs Ospedale Maggiore Di Milano

Milan, 20122, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56124, Italy

Location

Hiroshima University Hospital

Hiroshima, 734-8551, Japan

Location

Musashino Red Cross Hospital

Musashino, 180-8610, Japan

Location

National Hospital Organization Nagasaki Medical Center

Nagasaki, 856-8562, Japan

Location

Nagoya City University Hospital

Nagoya, 467-8602, Japan

Location

Osaka University Hospital

Suita-shi, 565-0871, Japan

Location

Hospital Sultanah Bahiyah

Alor Star, 05460, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Szpital Specjalistyczny w Chorzowie

Chorzów, 41-500, Poland

Location

Wojewodzki Szpital Zespolony

Kielce, 25-317, Poland

Location

ID Clinic

Mysłowice, 41-400, Poland

Location

SP ZOZ Wroclawskie Centrum Zdrowia

Wroclaw, 50-136, Poland

Location

Medical Center SibNovoMed LLC

Novosibirsk, 630005, Russia

Location

Medical Company Hepatolog Ltd

Samara, 443063, Russia

Location

Stavropol State Medical University

Stavropol, 355017, Russia

Location

Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, 620102, Russia

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hosp. Clinic I Provincial de Barcelona

Barcelona, 8028, Spain

Location

Hosp. Univ. Vall D Hebron

Barcelona, 8035, Spain

Location

Hosp. Univ. Ramon Y Cajal

Madrid, 28034, Spain

Location

Hosp. Univ. Marques de Valdecilla

Santander, 39008, Spain

Location

Hosp. Virgen Del Rocio

Seville, 41013, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

Chang Gung Memorial Hospital Linkou Branch

Taoyuan District, 333, Taiwan

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10500, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Chiang Mai University Hospital

Chiang Mai, 50200, Thailand

Location

Prince Of Songkla University

Songkhla, 90110, Thailand

Location

Istanbul University Cerrahpasa Medical Faculty

Istanbul, 34098, Turkey (Türkiye)

Location

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

Istanbul, 34371, Turkey (Türkiye)

Location

Ege University Medical of Faculty, Department of Gastroenterology

Izmir, 35100, Turkey (Türkiye)

Location

Karadeniz Teknik University Medical Faculty

Trabzon, 61080, Turkey (Türkiye)

Location

Kharkiv National Medical University, Regional Clinical Infectious Hospital

Kharkiv, 61000, Ukraine

Location

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

Kharkiv, 61039, Ukraine

Location

Odessa Regional Clinical Hospital

Odesa, 65025, Ukraine

Location

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

Vinnytsia, 21021, Ukraine

Location

North Manchester General Hospital

Crumpsall, M8 5RB, United Kingdom

Location

Grahame Hayton Unit

London, E1 1BB, United Kingdom

Location

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 37385475 DERIVED

• 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.

  PMID: 36697207 DERIVED

• 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.

  PMID: 32094138 DERIVED

MeSH Terms

Conditions

Hepatitis B

Interventions

JNJ-56136379; Sodium; entecavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Results Point of Contact

• Title: Senior Director
• Organization: Janssen Sciences Ireland UC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Sciences Ireland UC Clinical Trial

  Janssen Sciences Ireland UC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2017
• First Posted: December 5, 2017
• Study Start: February 13, 2018
• Primary Completion: September 5, 2019
• Study Completion: August 13, 2020
• Last Updated: November 17, 2022
• Results First Posted: November 17, 2022

Record last verified: 2022-10

Locations

GB (4); MY (2); DE (4); UA (4); TW (4); KR (4); TU (4); RU (4); IT (3); HK (2); BE (3); US (7); CN (4); FR (4); JP (5); TH (4); ES (5); PL (4); CA (5)