A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection (REEF-1)
January 31, 2025 updated by: Janssen Sciences Ireland UC
A Phase 2b, Multicenter, Double-blind, Active-controlled, Randomized Study to Investigate the Efficacy and Safety of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection
The purpose of this study is to establish the dose-response relationship for antiviral activity of 3 dose levels of JNJ-73763989+nucleos(t)ide analog (NA) and to evaluate the efficacy of combination regimens of JNJ-73763989+NA (with and without JNJ-56136379) and of JNJ-56136379+NA.
Study Overview
Status
Completed
Conditions
Detailed Description
Hepatitis B virus (HBV) is a small deoxyribonucleic acid virus that specifically infects the human liver.
The acute phase of infection is either followed by an immune controlled state or progresses to chronic hepatitis B. The worldwide estimated prevalence of chronic HBV infection is about 292 million people affected.
Hepatitis B surface antigen (HBsAg) seroclearance is currently considered to be associated with the most thorough suppression of HBV replication (termed functional cure).
With current available NA treatment strategies, rate of HBsAg seroclearance remains very low (around 3 percent [%]) even under long-term treatment.
Also, with the persistently high global prevalence of HBV-associated mortality, there is a medical need for more effective finite treatment options that lead to sustained HBsAg seroclearance.
JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via ribonucleic acid interference mechanism.
JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for the treatment of chronic HBV infection.
The aim of the study is to evaluate efficacy as measured by proportion of participants who completed 48-week study intervention and qualified for stopping NA treatment at Week 48.
The study includes: Screening phase (4 weeks), Double-blind study intervention phase (from Day 1 up to Week 48), and Follow-up phase (48 weeks after end of investigational intervention with a maximum duration of 96 weeks).
The duration of individual study participation will be between 100 and 150 weeks.
Safety and tolerability (including adverse events [AEs] and Serious AEs, laboratory assessments, electrocardiogram [ECG], vital signs, physical examination), efficacy (including HBsAg seroclearance), and pharmacokinetics will be assessed throughout the study.
Study Type
Interventional
Enrollment (Actual)
471
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Bruxelles, Belgium, 1200
- Cliniques Universitaires Saint Luc
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Edegem, Belgium, 2650
- UZ Antwerpen
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Edegem, Belgium, 2650
- UZA-SGS
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Gent, Belgium, 9000
- Universitair Ziekenhuis Gent
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Leuven, Belgium, 3000
- UZ Leuven
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Manaus, Brazil, 69040-000
- Fundacao de Medicina Tropical Doutor Heitor Vieira Dourado - FMT
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Salvador, Brazil, 40110-060
- Universidade Federal da Bahia - Hospital Professor Edgard Santos
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Sao Paulo, Brazil, 05403-000
- Hospital das Clínicas da Faculdade de Medicina da USP
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Alberta
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Calgary, Alberta, Canada, T2N 4Z6
- University Of Calgary
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Edmonton, Alberta, Canada, T6G 2G3
- University of Alberta - Faculty of Medicine & Dentistry
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British Columbia
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Vancouver, British Columbia, Canada, V6Z 2K5
- GI Research Institute (G.I.R.I.)
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Vancouver, British Columbia, Canada, V6Z2C7
- Vancouver ID Research and Care Centre Society
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Ontario
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Toronto, Ontario, Canada, ON M5G 2C4
- Toronto General Hospital
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Guangzhou, China, 510515
- Nanfang Hospital
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Hradec Kralove, Czechia, 500 05
- FN Hradec Kralove
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Plzen, Czechia, 32600
- Research Site s.r.o.
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Praha, Czechia, 140 21
- IKEM
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Praha 2, Czechia, 120 00
- KLIN MED s.r.o
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Clichy, France, 92110
- Hôpital Beaujon
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Grenoble, France, 38043
- CHU de Grenoble Hopital Albert Michallon
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Lyon, France, 69004
- Hopital de la croix rousse
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Marseille, France, 13008
- Hôpital Saint Joseph
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Nantes, France, 44093
- CHU de Nantes hotel Dieu
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Paris, France, 75012
- Hôpital Saint-Antoine
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Rennes, France, 35033
- Chu Rennes Hopital Pontchaillou
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Villejuif, France, 94800
- Hôpital Paul Brousse
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Berlin, Germany, 10787
- Epimed GmbH
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Essen, Germany, 45147
- Universitatsklinikum Essen
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Frankfurt, Germany, 60590
- Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
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Hamburg, Germany, 20146
- ICH Study Center GmbH & Co. KG
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Hamburg, Germany, D-20246
- University Medical Center
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Hannover, Germany, 30625
- Medizinische Hochschule Hannover
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Leipzig, Germany, 04103
- Universitaetsklinikum Leipzig
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Mainz, Germany, 55131
- Universitatsmedizin der Johannes Gutenberg Universitat Mainz
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Hong Kong, Hong Kong
- The University of Hong Kong
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Shatin, Hong Kong
- The Chinese University of Hong Kong
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Messina, Italy, 98124
- Azienda Ospedaliera Universitaria Policlinico G. Martino
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Milano, Italy, 20122
- Irccs Ospedale Maggiore Di Milano
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Modena, Italy, 41126
- Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara
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Pisa, Italy, 56124
- Azienda Ospedaliero Universitaria Pisana
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Rome, Italy, 00161
- Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma
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Bunkyo Ku, Japan, 113 8519
- Tokyo Medical and Dental University Hospital
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Chiba, Japan, 260 8677
- Chiba University Hospital
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Fukui City, Japan, 918-8503
- Fukui-ken Saiseikai Hospital
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Fukuyama, Japan, 721-8511
- Fukuyama City Hospital
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Hiroshima shi, Japan, 734 8551
- Hiroshima University Hospital
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Kagawa, Japan, 760-8557
- Kagawa Prefectural Central Hospital
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Kashihara, Japan, 634-8522
- Nara Medical University Hospital
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Musashino, Japan, 180-8610
- Musashino Red Cross Hospital
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Nagasaki, Japan, 856-8562
- National Hospital Organization Nagasaki Medical Center
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Nagoya, Japan, 467 8602
- Nagoya City University Hospital
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Nishinomiya, Japan, 663-8501
- The Hospital of Hyogo College of Medicine
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Sapporo-shi, Japan, 060-8648
- Hokkaido University Hospital
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Suita-shi, Japan, 565-0871
- Osaka University Hospital
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Tokyo, Japan, 105-8470
- Toranomon Hospital
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Toyoake, Japan, 470-1192
- Fujita Health University Hospital
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Seoul, Korea, Republic of, 03080
- Seoul National University Hospital
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Seoul, Korea, Republic of, 05505
- Asan Medical Center
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Seoul, Korea, Republic of, 03722
- Severance Hospital Yonsei University Health System
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Seoul, Korea, Republic of, 06351
- Samsung Medical Center
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Alor Setar, Malaysia, 05460
- Hospital Sultanah Bahiyah
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Batu Caves, Malaysia, 68100
- Hospital Selayang
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Kota Bharu, Malaysia, 16150
- Hospital University Sains Malaysia
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Kuala Lumpur, Malaysia, 59100
- University Malaya Medical Centre
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Bydgoszcz, Poland, 85-030
- Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy
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Gdansk, Poland, 80-462
- Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska
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Myslowice, Poland, 41-400
- ID Clinic
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Warszawa, Poland, 01-201
- Wojewódzki Szpital Zakaźny w Warszawie
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Wroclaw, Poland, 50-136
- SP ZOZ Wroclawskie Centrum Zdrowia
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Chelyabinsk, Russian Federation, 454092
- Ural State Medical University
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Ekaterinburg, Russian Federation, 620102
- Sverdlovsk Regional Clinical Hospital #1
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Krasnoyarsk, Russian Federation, 660049
- Krasnoyarsk Regional Center For AIDS And Infectious Diseases Treatment And Prophylaxis
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Moscow, Russian Federation, 121170
- Clinic of the Modern Medicine
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Novosibirsk, Russian Federation, 630005
- Medical Center SibNovoMed LLC
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Saint Petersburg, Russian Federation, 190103
- St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis
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Saint Petersburg, Russian Federation, 196645
- Republican Clinical Infectious Hospital
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Saint-Petersburg, Russian Federation, 195067
- Clinical Infectious Diseases Hospital n. a. S.P. Botkin
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Samara, Russian Federation, 443063
- Medical Company Hepatolog Ltd
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Smolensk, Russian Federation, 214018
- Smolensk Regional Clinical Hospital
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Stavropol, Russian Federation, 355017
- Stavropol State Medical University
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Barcelona, Spain, 08028
- Hosp Clinic de Barcelona
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Barcelona, Spain, 8035
- Hosp Univ Vall D Hebron
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Madrid, Spain, 28041
- Hosp. Univ. 12 de Octubre
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Madrid, Spain, 28222
- Hospital Puerta de Hierro
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Santander, Spain, 39008
- Hosp. Univ. Marques de Valdecilla
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Valencia, Spain, 46014
- Hosp. Gral. Univ. Valencia
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Bangkok, Thailand, 10700
- Siriraj Hospital
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Bangkok, Thailand, 10500
- King Chulalongkorn Memorial Hospital
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Chiang Mai, Thailand, 50200
- Chiang Mai University Hospital
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Songkla, Thailand, 90110
- Prince of Songkla University
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Ankara, Turkey, 06230
- Hacettepe University Hospital
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Ankara, Turkey, 06620
- Ankara University Medical Faculty
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Ankara, Turkey, 6800
- Ankara Bilkent Şehir Hastanesi
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Istanbul, Turkey, 34098
- Istanbul University Cerrahpasa Medical Faculty
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Izmir, Turkey, 35100
- Ege University Medical of Faculty, Department of Gastroenterology
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Trabzon, Turkey, 61080
- Karadeniz Teknik University Medical Faculty
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Glasgow, United Kingdom, G12 0YN
- NHS Greater Glasgow and Clyde - Gartnavel General Hospital
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London, United Kingdom, E1 1BB
- Grahame Hayton Unit
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London, United Kingdom, SE5 9RF
- Kings College Hospital
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London, United Kingdom, SW17 0RE
- St Georges University of London and St George's University Hospitals NHS Foundation Trust
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California
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Bakersfield, California, United States, 93301
- The Office of Franco Felizarta, MD
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Los Angeles, California, United States, 90036
- Ruane Clinical Research Group Inc
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San Clemente, California, United States, 92673
- Southern California GI and Liver Center
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District of Columbia
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Washington, District of Columbia, United States, 20016
- Johns Hopkins Office of Capital Region Research - Sibley Memorial Hospital
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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New Jersey
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Hillsborough, New Jersey, United States, 08844
- I.D. Care, Inc.
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New York
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New York, New York, United States, 10016
- NYU Hepatology Associates
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
14 years to 61 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 surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
- Body mass index (BMI) between 18.0 and 35.0 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
- 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
- Participants with known allergies, hypersensitivity, or intolerance to JNJ-3989 and JNJ 6379 or their excipients or excipients of the 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
- Female participants who are pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study intervention
- Male participants who plan to father a child while enrolled
- Participants who had or planned major surgery, (example, requiring general anesthesia) or who have received an organ transplant
- Vulnerable participants (example, incarcerated individuals, individuals under a legal protection measure)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Arm 1: JNJ-73763989 (medium dose) + JNJ-56136379 + NA
Participants will receive medium dose of JNJ-73763989 along with JNJ-56136379 and nucleos(t)ide analog (NA) treatment (either entecavir [ETV], tenofovir disoproxil fumarate [TDF], or tenofovir alafenamide [TAF]) up to 48 weeks.
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JNJ-56136379 tablets will be administered orally.
JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection.
NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.
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Experimental: Arm 2: JNJ-73763989 (high dose) + Placebo + NA
Participants will receive high dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks.
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JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection.
NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.
Placebo for JNJ-56136379 tablets will be administered orally.
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Experimental: Arm 3: JNJ-73763989 (medium dose) + Placebo + NA
Participants will receive medium dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks.
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JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection.
NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.
Placebo for JNJ-56136379 tablets will be administered orally.
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Experimental: Arm 4: JNJ-73763989 (low dose) + Placebo + NA
Participants will receive low dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks.
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JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection.
NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.
Placebo for JNJ-56136379 tablets will be administered orally.
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Experimental: Arm 5: Placebo + JNJ-56136379 + NA
Participants will receive placebo for JNJ-73763989 and a fixed dose of JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks.
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JNJ-56136379 tablets will be administered orally.
NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.
Placebo for JNJ-73763989 will be administered as subcutaneous injection.
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Placebo Comparator: Arm 6 (Control): Placebo + Placebo + NA
Participants will receive placebo for JNJ-73763989 and placebo for JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks.
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NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.
Placebo for JNJ-56136379 tablets will be administered orally.
Placebo for JNJ-73763989 will be administered as subcutaneous injection.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Percentage of Participants Meeting the Nucleos(t)Ide Analog (NA) Treatment Completion Criteria at Week 48
Time Frame: Week 48
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Percentage of participants meeting the NA treatment completion criteria at Week 48 were reported.
A participant was defined as a responder in meeting the NA treatment completion criteria at Week 48, if the following criteria were met based on the clinical laboratory tests performed at Week 44: participants had alanine transaminase (ALT) less than (<) 3*upper limit of normal range (ULN); had hepatitis B virus deoxyribonucleic acid (HBV DNA) < lower limit of quantification (LLOQ); was hepatitis B e antigen (HBeAg)-negative; had hepatitis B surface antigen (HBsAg) <10 international units per milliliter (IU/mL).
Multiple Imputation using a longitudinal multiple regression model was applied to impute missing data.
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Week 48
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Double-blind Phase: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
Time Frame: Baseline up to Week 48
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An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product.
An AE does not necessarily have a causal relationship with the intervention.
Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.
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Baseline up to Week 48
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Follow-up Phase 1: Percentage of Participants With TEAEs
Time Frame: From Week 48 up to Week 96
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An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product.
An AE does not necessarily have a causal relationship with the intervention.
Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.
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From Week 48 up to Week 96
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Follow-up Phase 2: Percentage of Participants With TEAEs
Time Frame: From Week 48 up to Week 96
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An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product.
An AE does not necessarily have a causal relationship with the intervention.
Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.
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From Week 48 up to Week 96
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Follow-up Phase 3: Percentage of Participants With TEAEs
Time Frame: From Week 48 up to Week 96
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An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product.
An AE does not necessarily have a causal relationship with the intervention.
Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.
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From Week 48 up to Week 96
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Extended Follow-up Phase: Percentage of Participants With TEAEs
Time Frame: Extended Follow up Week 1 to extended follow up Week 48
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An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product.
An AE does not necessarily have a causal relationship with the intervention.
Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.
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Extended Follow up Week 1 to extended follow up Week 48
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Double-blind Phase: Percentage of Participants With Serious Adverse Events (SAEs)
Time Frame: Baseline up to Week 48
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An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.
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Baseline up to Week 48
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Follow-up Phase 1: Percentage of Participants With SAEs
Time Frame: From Week 48 up to Week 96
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An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.
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From Week 48 up to Week 96
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Follow-up Phase 2: Percentage of Participants With SAEs
Time Frame: From Week 48 up to Week 96
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An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.
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From Week 48 up to Week 96
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Follow-up Phase 3: Percentage of Participants With SAEs
Time Frame: From Week 48 up to Week 96
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An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.
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From Week 48 up to Week 96
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Extended Follow-up Phase: Percentage of Participants With SAEs
Time Frame: Extended Follow up Week 1 to extended follow up Week 48
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An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.
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Extended Follow up Week 1 to extended follow up Week 48
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Percentage of Participants With Abnormalities in Clinical Laboratory Tests (Hematology)
Time Frame: Double blind (DB) phase: Baseline (Day 1) up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
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Percentage of participants with abnormalities in clinical laboratory tests (hematology: Abnormally low [AL] and Abnormally high [AH] basophils, eosinophils, erthrocytes mean corpuscular hemoglobin concentration, erthrocytes mean corpuscular heamoglobin, erthrocytes mean corpuscular volume, erthrocytes, hematocrit, lymphocytes atypical, metamyelocytes, monocytes, myelocytes, neutrophils, segmented, reticulocytes) were reported.
Abnormality was determined at the investigator's discretion.
Here, M.C: Mean corpuscular.
Participants with abnormally low or high values were reported.
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Double blind (DB) phase: Baseline (Day 1) up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
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Percentage of Participants With Abnormalities in Clinical Laboratory Tests (Chemistry)
Time Frame: Double blind (DB) phase: Baseline up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
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Percentage of participants with abnormalities in clinical laboratory tests (Chemistry: abnormally high and serum alpha fetoprotein, serum chloride, Serum gamma glutamyl tranferase [GGT], Serum high density cholesterol [HDL] Cholesterol, Indirect Bilirubin, Lactate Dehydrogenase, Serum Protein, Urea Nitrogen) were reported.
Abnormality was determined at the investigator's discretion.
Participants with abnormally low or high values were reported.
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Double blind (DB) phase: Baseline up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
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Percentage of Participants With Abnormalities in Clinical Laboratory Tests (Urinalysis)
Time Frame: Double blind (DB) phase: Baseline up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
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Percentage of participants with abnormalities in clinical laboratory tests(Urinalysis: abnormally high and low urine granular casts, urine hyaline casts, Urine Leukocytes,Urine Specific Gravity,Urine Squamous Epithelial cell, Urine T.E Cells, Urine Transitinoal erythrocyte count [E.C],Urine Tubular erthrocyte count ) were reported.
Abnormality was determined at the investigator's discretion.
Participants with abnormally low or high values were reported.
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Double blind (DB) phase: Baseline up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
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Percentage of Participants With Abnormalities in Electrocardiogram (ECG)
Time Frame: Double blind (DB) phase: Baseline (Day 1) up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
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Percentage of participants with abnormalities in ECG parameters (heart rate, PR interval, QRS duration, and QTcF interval) were reported.
Abnormality criteria: Heart rate abnormally low (AL): <45 beats per minute (bpm); PR interval AH:>220 msec; QRS duration AH:>120 msec; QTcF borderline prolonged (BP) QT: 450 msec to <=480 msec.
Participants with abnormally low or high values were reported.
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Double blind (DB) phase: Baseline (Day 1) up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
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Percentage of Participants With Abnormalities in Vital Signs
Time Frame: Double blind (DB) phase: Baseline (Day 1) up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
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Percentage of participants with abnormalities in vital signs parameters (pulse rate, diastolic and systolic blood pressure) were reported.
Abnormality criteria: Pulse rate AL:<=45 bpm; Systolic blood pressure (SBP) AL: <=90 millimeters of mercury (mmHg), mild:>140 mmHg to <160 mmHg; moderate:>=160 mmHg to <180 mmHg; Diastolic blood pressure (DBP): AL: <=150 mmHg; mild:>90 mmHg to <100 mmHg; moderate: >=100 mmHg to <110 mmHg; severe:>=110 mmHg.
Abnormality was determined at the investigator's discretion.
Participants with abnormally low or high values were reported.
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Double blind (DB) phase: Baseline (Day 1) up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
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Percentage of Participants With HBsAg Seroclearance 24 Weeks After Completion of All Study Intervention at Week 48
Time Frame: Week 72
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Percentage of participants with HBsAg seroclearance 24 weeks after completion of all study intervention at Week 48 were reported.
HBsAg seroclearance was defined as HBsAg (less than [<] lower limit of quantification LLOQ [0.05 IU/mL]).
Responder was defined as a participant who achieved functional cure at Week 72.
A participant was defined as having achieved functional cure at Week 72 if he/she: had met the criteria for stopping NA treatment at Week 48 and stopped treatment; had HBsAg seroclearance at Week 72 (that is, 24 weeks after stopping all study interventions); did not require NA re-treatment between Weeks 48 and 72.
Multiple Imputation using a longitudinal multiple regression model was applied to impute missing data.
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Week 72
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Percentage of Participants With HBsAg Seroclearance 48 Weeks After Completion of All Study Intervention at Week 48
Time Frame: Week 96
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Percentage of participants with HBsAg seroclearance 48 weeks after completion of all study intervention at Week 48 were reported.
HBsAg Seroclearance was defined as HBsAg <LLOQ (0.05 IU/mL).
A responder was defined as a participant who achieved HBsAg seroclearance at Week 96 if the participant completed 48 weeks of treatment, met the criteria for stopping NA treatment at Week 48, did not require NA re-treatment between Week 48 and Week 96, and had HBsAg seroclearance at Week 96.
Multiple Imputation using a longitudinal multiple regression model was applied to impute missing data.
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Week 96
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Percentage of Participants With HBV DNA <LLOQ 24 and 48 Weeks After Completion of All Study Intervention at Week 48
Time Frame: Weeks 72 and 96
|
Percentage of participants with HBV DNA <LLOQ at 24 and 48 weeks after completion of all study intervention at Week 48 were reported.
A responder was defined as a participant who achieved HBV DNA <LLOQ 24 and 48 weeks after stopping all study treatments at any time during the study and without restarting NA treatment thereafter.
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Weeks 72 and 96
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Percentage of Participants Meeting the NA Treatment Completion Criteria During Follow-up
Time Frame: Week 48 up to Week 96
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Percentage of participants meeting the NA treatment completion criteria during follow-up were reported.
A participant was defined as a responder in meeting the NA treatment completion criteria at Week 48, if the following criteria were met based on the clinical laboratory tests performed at Week 44: participants had alanine transaminase (ALT) less than (<) 3*upper limit of normal range (ULN); had hepatitis B virus deoxyribonucleic acid (HBV DNA) < lower limit of quantification (LLOQ); was hepatitis B e antigen (HBeAg)-negative; had hepatitis B surface antigen (HBsAg) <10 international units per milliliter (IU/mL).
A responder was defined as a participant who stopped NA at Week 48 and met the NA treatment completion criteria at any time during the follow-up phase, regardless of the treatment duration.
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Week 48 up to Week 96
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Percentage of Participants With HBsAg Seroclearance After Completion of NA Treatment at Weeks 60, 84, and 96
Time Frame: Weeks 60, 84, and 96
|
Percentage of participants with HBsAg seroclearance after completion of NA treatment at Weeks 60, 84, and 96 were reported.
Seroclearance of HBsAg was defined as HBsAg level <LLOQ (0.05 IU/mL).
For Week 60: a responder was defined as a participant who achieved HBsAg seroclearance 12 weeks off treatment if the subject achieved HBsAg seroclearance 12 weeks after stopping; for Week 84:A responder was defined as a participant who achieved HBsAg seroclearance 36 weeks off-treatment if the participant achieved HBsAg seroclearance 36 weeks after stopping all study treatments; for Week 96:A responder was defined as a participant who achieved HBsAg seroclearance at Week 96 if the participant completed 48 weeks of treatment, met the criteria for stopping NA treatment at Week 48, did not require NA re-treatment between Week 48 and Week 96, and had HBsAg seroclearance at Week 96.
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Weeks 60, 84, and 96
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Percentage of Participants Who Required NA Re-treatment During Follow-up
Time Frame: Week 48 up to Week 96
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Percentage of participants who required NA re-treatment during follow-up were reported.
Responder was defined as a participant who met the criteria for NA re-treatment at any time during follow-up, for those participants who met the NA treatment completion criteria at any time during the study and actually stopped NA treatment.
NA re-treatment criteria: (1) Re-start NA treatment immediately with signs of decreasing liver function based on laboratory findings (eg, International Normalized Ratio [INR], direct bilirubin) or clinical assessment (eg, ascites, hepatic encephalopathy).
(2) Immediately with an HBV DNA value of >100,000 IU/mL (irrespective of confirmation and/or ALT increase).
(3) With confirmed post-treatment HBeAg seroreversion (HBeAg positive after it was negative at NA completion) (4) With confirmed* post-treatment increases in HBV DNA >2,000 IU/mL and ALT >5x ULN (5) With confirmed* post-treatment increases in HBV DNA >20,000 IU/mL.
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Week 48 up to Week 96
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Percentage of Participants With Flares
Time Frame: Follow-up phase (Week 48 up to Week 96)
|
Percentage of participants with flares (virologic, biochemical, and clinical) were reported.
Virologic flare: confirmed HBV DNA >peak threshold ( 20,000 IU/mL 2,000 IU/mL and 200 IU/mL); biochemical Flare: confirmed ALT and/or AST increase of 3*ULN and 3*nadir; clinical flare: confirmed HBV DNA >peak threshold and confirmed ALT and/or AST increase of 3*ULN and 3*nadir.
Virologic and clinical flare was assessed only for those participants who were off-treatment and had HBV DNA<LLOQ at the last observed time point on all study treatments and biochemical flares was identified on treatment and off treatment, respectively.
Each virologic flare was categorized based on the confirmed (i.e., two consecutive values) peak HBV DNA above any of the three thresholds within the start and end date of that flare as follows: 20,000 IU/mL 2,000 IU/mL and 200 IU/mL.
A participant was defined as off-treatment failure if he/she required NA re-treatment after stopping all study interventions.
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Follow-up phase (Week 48 up to Week 96)
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Number of Participants With (Sustained) Reduction, Suppression, and/or Seroclearance Considering Single and Multiple Marker
Time Frame: Weeks 12, 24, 36 and 48
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Number of participants with (sustained) reduction considering multiple markers were reported.
HBV DNA results <LLOQ were reported as: (a) target detected, that is, traces of HBV DNA were detected/found but were too low to be quantified, or (b) target not detected, that is, no traces of HBV DNA were detected/found.
LLOQ value for HBV DNA was 20 IU/mL.
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Weeks 12, 24, 36 and 48
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Percentage of Participants With HBsAg Seroconversion
Time Frame: Weeks 48, 60, 72, and 96
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HBsAg seroconversion was defined as achieving HBsAg seroclearance (HBsAg [quantitative] <LLOQ [0.05 IU/mL]) together with an appearance of anti-HBs antibodies (baseline anti-HBs antibodies [quantitative] <LLOQ and a post-baseline assessment greater than or equal to [>=] LLOQ).
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Weeks 48, 60, 72, and 96
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Percentage of Participants With HBeAg Seroconversion
Time Frame: Weeks 48, 60, 72, and 96
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HBeAg seroconversion was defined as achieving HBeAg seroclearance (HBeAg [quantitative] <LLOQ) together with an appearance of anti-HBe antibodies (baseline anti-HBe antibodies [qualitative] with a "negative" result and a post-baseline assessment with "positive" result.
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Weeks 48, 60, 72, and 96
|
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Change From Baseline in HBsAg Levels
Time Frame: Baseline, Weeks 12, 24, 48, 60, 72, 96
|
Change from baseline in HBsAg levels was reported.
|
Baseline, Weeks 12, 24, 48, 60, 72, 96
|
|
Change From Baseline in HBeAg Levels
Time Frame: Baseline, Weeks 12, 24, 48, 60, 72, 96
|
Change from baseline in HBeAg levels was reported.
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Baseline, Weeks 12, 24, 48, 60, 72, 96
|
|
Change From Baseline in HBV DNA Levels
Time Frame: Baseline, Weeks 12, 24, 48, 60, 72, 96
|
Change from baseline in HBV DNA levels were reported.
|
Baseline, Weeks 12, 24, 48, 60, 72, 96
|
|
Time to Achieve HBsAg Seroclearance
Time Frame: Baseline (Day 1) up to Week 96
|
Time to HBsAg seroclearance (defined as HBsAg level <LLOQ [0.05 IU/mL]) was defined as the number of days between the date of first study treatment intake and the date of the first occurrence of HBsAg seroclearance.
|
Baseline (Day 1) up to Week 96
|
|
Time to Achieve HBeAg Seroclearance
Time Frame: Baseline (Day 1) up to Week 96
|
Time to HBeAg seroclearance (defined as HBeAg level <LLOQ [0.11 IU/mL]) was defined as the number of days between the date of first study treatment intake and the date of the first occurrence of HBeAg seroclearance.
|
Baseline (Day 1) up to Week 96
|
|
Percentage of Participants With HBsAg Levels <100 IU/mL
Time Frame: Baseline, Weeks 12, 24, 48, 60, 72, 96
|
Percentage of participants with HBsAg levels <100 IU/mL was reported.
|
Baseline, Weeks 12, 24, 48, 60, 72, 96
|
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Percentage of Participants With HBsAg Levels >1 log10 IU/mL Reduction From Baseline
Time Frame: Weeks 12, 24, 48, 60, 72, 96
|
Percentage of participants with HBsAg levels >1 log10 IU/mL reduction from baseline was reported.
|
Weeks 12, 24, 48, 60, 72, 96
|
|
Percentage of HBeAg-positive Participants With HBeAg Levels <LLOQ
Time Frame: Weeks 12, 24, 48, 60, 72, 96
|
Percentage of HBeAg-positive participants with HBeAg levels <LLOQ were reported.
|
Weeks 12, 24, 48, 60, 72, 96
|
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Percentage of HBeAg-positive Participants With HBeAg Levels >1 log10 IU/mL
Time Frame: Weeks 12, 24, 48, 60, 72, 96
|
Percentage of HBeAg-positive partcipants with HBeAg levels >1 log10 IU/mL were reported.
|
Weeks 12, 24, 48, 60, 72, 96
|
|
Percentage of Participants With HBV DNA Levels <LLOQ
Time Frame: Baseline, Weeks 12, 24, 48, 60, 72, 96
|
Percentage of participants with HBV DNA levels <LLOQ (20 IU/mL) were reported.
|
Baseline, Weeks 12, 24, 48, 60, 72, 96
|
|
Mean Change From Baseline in ALT at EOT (Week 48) in Participants With Elevated ALT at Baseline
Time Frame: Baseline and Week 48
|
Mean change from baseline in ALT at EOT (Week 48) in participants with elevated ALT at baseline were reported.
|
Baseline and Week 48
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Percentage of Participants With ALT Normalization
Time Frame: Baseline, Weeks 12, 24, 48, 60, 72, 96
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Percentage of participants with ALT normalization was reported.
A participant with ALT elevation at baseline was considered to achieve ALT normalization if his/her ALT value was <ULN at any given postbaseline analysis time point.
A participant was defined as on treatment failure if he/she never met the criteria for stopping NA treatment during the study.
A participant was defined as off-treatment failure if he/she required NA re-treatment after stopping all study interventions.
|
Baseline, Weeks 12, 24, 48, 60, 72, 96
|
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Percentage of Participants With Virologic Breakthrough
Time Frame: Baseline (Day 1) up to Week 48
|
Virologic breakthrough was defined as having a confirmed on-treatment HBV DNA increase by >1 log10 from nadir (that is, lowest value during treatment) or a confirmed HBV DNA level >200 IU/mL in participants who had on-treatment HBV DNA level below the LLOQ (20 IU/mL).
On-treatment was defined as the time period in which the participant received any of the study intervention.
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Baseline (Day 1) up to Week 48
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Percentage of Participants With Undetectable HBV DNA Levels After Re-start of NA Treatment During Follow-up
Time Frame: Week 48 up to Week 96
|
Percentage of participants with undetectable HBV DNA levels after re-start of NA treatment during follow-up was reported.
|
Week 48 up to Week 96
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Janssen Sciences Ireland UC Clinical Trial, Janssen Sciences Ireland UC
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 1, 2019
Primary Completion (Actual)
March 29, 2021
Study Completion (Actual)
April 26, 2022
Study Registration Dates
First Submitted
June 10, 2019
First Submitted That Met QC Criteria
June 10, 2019
First Posted (Actual)
June 11, 2019
Study Record Updates
Last Update Posted (Actual)
March 25, 2025
Last Update Submitted That Met QC Criteria
January 31, 2025
Last Verified
January 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
- 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
- Virus Diseases
- Herpesviridae Infections
- Anti-Infective Agents
- Antiviral Agents
- JNJ-56136379
Other Study ID Numbers
- CR108608
- 2019-000622-22 (EudraCT Number)
- 73763989HPB2001 (Other Identifier: Janssen Sciences Ireland UC)
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.