A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection

NCT ID: NCT03982186

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 471 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-01
• Study Completion Date: 2022-04-26

Brief Summary

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.

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.

Conditions

Hepatitis B, Chronic

Study Design

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

Study Groups

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.

Group Type: EXPERIMENTAL

JNJ-73763989

Intervention Type: DRUG

JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection.

JNJ-56136379

Intervention Type: DRUG

JNJ-56136379 tablets will be administered orally.

Nucleos(t)ide Analog (NA)

Intervention Type: DRUG

NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.

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.

Group Type: EXPERIMENTAL

JNJ-73763989

Intervention Type: DRUG

JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection.

Placebo for JNJ-56136379

Intervention Type: DRUG

Placebo for JNJ-56136379 tablets will be administered orally.

Nucleos(t)ide Analog (NA)

Intervention Type: DRUG

NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.

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.

Group Type: EXPERIMENTAL

JNJ-73763989

Intervention Type: DRUG

JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection.

Placebo for JNJ-56136379

Intervention Type: DRUG

Placebo for JNJ-56136379 tablets will be administered orally.

Nucleos(t)ide Analog (NA)

Intervention Type: DRUG

NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.

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.

Group Type: EXPERIMENTAL

JNJ-73763989

Intervention Type: DRUG

JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection.

Placebo for JNJ-56136379

Intervention Type: DRUG

Placebo for JNJ-56136379 tablets will be administered orally.

Nucleos(t)ide Analog (NA)

Intervention Type: DRUG

NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.

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.

Group Type: EXPERIMENTAL

Placebo for JNJ-73763989

Intervention Type: DRUG

Placebo for JNJ-73763989 will be administered as subcutaneous injection.

JNJ-56136379

Intervention Type: DRUG

JNJ-56136379 tablets will be administered orally.

Nucleos(t)ide Analog (NA)

Intervention Type: DRUG

NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.

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.

Group Type: PLACEBO_COMPARATOR

Placebo for JNJ-73763989

Intervention Type: DRUG

Placebo for JNJ-73763989 will be administered as subcutaneous injection.

Placebo for JNJ-56136379

Intervention Type: DRUG

Placebo for JNJ-56136379 tablets will be administered orally.

Nucleos(t)ide Analog (NA)

Intervention Type: DRUG

NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.

Interventions

JNJ-73763989

JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection.

Intervention Type: DRUG

Placebo for JNJ-73763989

Placebo for JNJ-73763989 will be administered as subcutaneous injection.

Intervention Type: DRUG

JNJ-56136379

JNJ-56136379 tablets will be administered orally.

Intervention Type: DRUG

Placebo for JNJ-56136379

Placebo for JNJ-56136379 tablets will be administered orally.

Intervention Type: DRUG

Nucleos(t)ide Analog (NA)

NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 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

Ruane Clinical Research Group Inc

Los Angeles, California, United States

Southern California GI and Liver Center

San Clemente, California, United States

Johns Hopkins Office of Capital Region Research - Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Johns Hopkins University

Baltimore, Maryland, United States

Washington University School Of Medicine

St Louis, Missouri, United States

I.D. Care, Inc.

Hillsborough, New Jersey, United States

NYU Hepatology Associates

New York, New York, United States

Cliniques Universitaires Saint Luc

Brussels, , Belgium

UZ Antwerpen

Edegem, , Belgium

UZA-SGS

Edegem, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

Fundacao de Medicina Tropical Doutor Heitor Vieira Dourado - FMT

Manaus, , Brazil

Universidade Federal da Bahia - Hospital Professor Edgard Santos

Salvador, , Brazil

Hospital Das Clinicas Da Faculdade De Medicina Da USP

São Paulo, , Brazil

University of Calgary

Calgary, Alberta, Canada

University of Alberta - Faculty of Medicine & Dentistry

Edmonton, Alberta, Canada

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

Vancouver, British Columbia, Canada

Vancouver ID Research and Care Centre Society

Vancouver, British Columbia, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Nanfang Hospital

Guangzhou, , China

FN Hradec Kralove

Hradec Králové, , Czechia

RESEARCH SITE s.r.o.

Pilsen, , Czechia

KLIN MED s.r.o

Prague, , Czechia

IKEM

Prague, , Czechia

Hopital Beaujon

Clichy, , France

CHU de Grenoble Hopital Albert Michallon

Grenoble, , France

Hopital de La Croix Rousse

Lyon, , France

Hopital Saint Joseph

Marseille, , France

CHU de Nantes hotel Dieu

Nantes, , France

Hopital Saint-Antoine

Paris, , France

Chu Rennes Hopital Pontchaillou

Rennes, , France

Hopital Paul Brousse

Villejuif, , France

EPIMED GmbH

Berlin, , Germany

Universitatsklinikum Essen

Essen, , Germany

Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1

Frankfurt, , Germany

ICH Study Center GmbH & Co. KG

Hamburg, , Germany

University Medical Center

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitaetsklinikum Leipzig

Leipzig, , Germany

Universitatsmedizin der Johannes Gutenberg Universitat Mainz

Mainz, , Germany

The University of Hong Kong

Hong Kong, , Hong Kong

The Chinese University of Hong Kong

Shatin, , Hong Kong

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, , Italy

Irccs Ospedale Maggiore Di Milano

Milan, , Italy

Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara

Modena, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma

Rome, , Italy

Tokyo Medical and Dental University Hospital

Bunkyō City, , Japan

Chiba University Hospital

Chiba, , Japan

Fukui-ken Saiseikai Hospital

Fukui, , Japan

Fukuyama City Hospital

Fukuyama, , Japan

Hiroshima University Hospital

Hiroshima, , Japan

Kagawa Prefectural Central Hospital

Kagawa, , Japan

Nara Medical University Hospital

Kashihara, , Japan

Musashino Red Cross Hospital

Musashino, , Japan

National Hospital Organization Nagasaki Medical Center

Nagasaki, , Japan

Nagoya City University Hospital

Nagoya, , Japan

The Hospital of Hyogo College of Medicine

Nishinomiya, , Japan

Hokkaido University Hospital

Sapporo, , Japan

Osaka University Hospital

Suita-shi, , Japan

Toranomon Hospital

Tokyo, , Japan

Fujita Health University Hospital

Toyoake, , Japan

Hospital Sultanah Bahiyah

Alor Star, , Malaysia

Hospital Selayang

Batu Caves, , Malaysia

Hospital University Sains Malaysia

Kota Bharu, , Malaysia

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy

Bydgoszcz, , Poland

Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska

Gdansk, , Poland

ID Clinic

Mysłowice, , Poland

Wojewodzki Szpital Zakazny w Warszawie

Warsaw, , Poland

SP ZOZ Wroclawskie Centrum Zdrowia

Wroclaw, , Poland

Ural State Medical University

Chelyabinsk, , Russia

Krasnoyarsk Regional Center For AIDS And Infectious Diseases Treatment And Prophylaxis

Krasnoyarsk, , Russia

Clinic of the Modern Medicine

Moscow, , Russia

Medical Center SibNovoMed LLC

Novosibirsk, , Russia

St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis

Saint Petersburg, , Russia

Clinical Infectious Diseases Hospital n. a. S.P. Botkin

Saint Petersburg, , Russia

Republican Clinical Infectious Hospital

Saint Petersburg, , Russia

Medical Company Hepatolog Ltd

Samara, , Russia

Smolensk Regional Clinical Hospital

Smolensk, , Russia

Stavropol State Medical University

Stavropol, , Russia

Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, , Russia

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hosp Clinic de Barcelona

Barcelona, , Spain

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Hospital Puerta De Hierro

Madrid, , Spain

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

Hosp. Gral. Univ. Valencia

Valencia, , Spain

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Siriraj Hospital

Bangkok, , Thailand

Chiang Mai University Hospital

Chiang Mai, , Thailand

Prince Of Songkla University

Songkhla, , Thailand

Hacettepe University Hospital

Ankara, , Turkey (Türkiye)

Ankara University Medical Faculty

Ankara, , Turkey (Türkiye)

Ankara Bilkent Sehir Hastanesi

Ankara, , Turkey (Türkiye)

Istanbul University Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Ege University Medical of Faculty, Department of Gastroenterology

Izmir, , Turkey (Türkiye)

Karadeniz Teknik University Medical Faculty

Trabzon, , Turkey (Türkiye)

NHS Greater Glasgow and Clyde - Gartnavel General Hospital

Glasgow, , United Kingdom

Grahame Hayton Unit

London, , United Kingdom

Kings College Hospital

London, , United Kingdom

St Georges University of London and St George's University Hospitals NHS Foundation Trust

London, , United Kingdom

Countries

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

References

Yuen MF, Asselah T, Jacobson IM, Brunetto MR, Janssen HLA, Takehara T, Hou JL, Kakuda TN, Lambrecht T, Beumont M, Kalmeijer R, Guinard-Azadian C, Mayer C, Jezorwski J, Verbinnen T, Lenz O, Shukla U, Biermer M; REEF-1 Study Group. Efficacy and safety of the siRNA JNJ-73763989 and the capsid assembly modulator JNJ-56136379 (bersacapavir) with nucleos(t)ide analogues for the treatment of chronic hepatitis B virus infection (REEF-1): a multicentre, double-blind, active-controlled, randomised, phase 2b trial. Lancet Gastroenterol Hepatol. 2023 Sep;8(9):790-802. doi: 10.1016/S2468-1253(23)00148-6. Epub 2023 Jul 10.

Reference Type: DERIVED

PMID: 37442152 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-000622-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

73763989HPB2001

Identifier Type: OTHER

Identifier Source: secondary_id

CR108608

Identifier Type: -

Identifier Source: org_study_id