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

NCT03982186 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: CR1086082019-000622-2273763989HPB2001
• Study Type: interventional
• Target: 471
• Locations: 19 countries
• Sites: 108

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.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Meeting the Nucleos(t)Ide Analog (NA) Treatment Completion Criteria at Week 48

  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.

  Week 48

Secondary Outcomes (39)

• Double-blind Phase: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)

  Baseline up to Week 48

• Follow-up Phase 1: Percentage of Participants With TEAEs

  From Week 48 up to Week 96

• Follow-up Phase 2: Percentage of Participants With TEAEs

  From Week 48 up to Week 96

• Follow-up Phase 3: Percentage of Participants With TEAEs

  From Week 48 up to Week 96

• Extended Follow-up Phase: Percentage of Participants With TEAEs

  Extended Follow up Week 1 to extended follow up Week 48

Study Arms (6)

Arm 1: JNJ-73763989 (medium dose) + JNJ-56136379 + NA

EXPERIMENTAL

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.

Drug: JNJ-73763989; Drug: JNJ-56136379; Drug: Nucleos(t)ide Analog (NA)

Arm 2: JNJ-73763989 (high dose) + Placebo + NA

EXPERIMENTAL

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.

Drug: JNJ-73763989; Drug: Placebo for JNJ-56136379; Drug: Nucleos(t)ide Analog (NA)

Arm 3: JNJ-73763989 (medium dose) + Placebo + NA

EXPERIMENTAL

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.

Drug: JNJ-73763989; Drug: Placebo for JNJ-56136379; Drug: Nucleos(t)ide Analog (NA)

Arm 4: JNJ-73763989 (low dose) + Placebo + NA

EXPERIMENTAL

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.

Drug: JNJ-73763989; Drug: Placebo for JNJ-56136379; Drug: Nucleos(t)ide Analog (NA)

Arm 5: Placebo + JNJ-56136379 + NA

EXPERIMENTAL

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.

Drug: Placebo for JNJ-73763989; Drug: JNJ-56136379; Drug: Nucleos(t)ide Analog (NA)

Arm 6 (Control): Placebo + Placebo + NA

PLACEBO COMPARATOR

Participants will receive placebo for JNJ-73763989 and placebo for JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks.

Drug: Placebo for JNJ-73763989; Drug: Placebo for JNJ-56136379; Drug: Nucleos(t)ide Analog (NA)

Interventions

JNJ-73763989 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.

Arm 1: JNJ-73763989 (medium dose) + JNJ-56136379 + NA; Arm 2: JNJ-73763989 (high dose) + Placebo + NA; Arm 3: JNJ-73763989 (medium dose) + Placebo + NA; Arm 4: JNJ-73763989 (low dose) + Placebo + NA

Placebo for JNJ-73763989 DRUG

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

Arm 5: Placebo + JNJ-56136379 + NA; Arm 6 (Control): Placebo + Placebo + NA

JNJ-56136379 DRUG

JNJ-56136379 tablets will be administered orally.

Arm 1: JNJ-73763989 (medium dose) + JNJ-56136379 + NA; Arm 5: Placebo + JNJ-56136379 + NA

Placebo for JNJ-56136379 DRUG

Placebo for JNJ-56136379 tablets will be administered orally.

Arm 2: JNJ-73763989 (high dose) + Placebo + NA; Arm 3: JNJ-73763989 (medium dose) + Placebo + NA; Arm 4: JNJ-73763989 (low dose) + Placebo + NA; Arm 6 (Control): Placebo + Placebo + NA

Nucleos(t)ide Analog (NA) DRUG

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

Arm 1: JNJ-73763989 (medium dose) + JNJ-56136379 + NA; Arm 2: JNJ-73763989 (high dose) + Placebo + NA; Arm 3: JNJ-73763989 (medium dose) + Placebo + NA; Arm 4: JNJ-73763989 (low dose) + Placebo + NA; Arm 5: Placebo + JNJ-56136379 + NA; Arm 6 (Control): Placebo + Placebo + NA

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Sciences Ireland UC: lead

Study Sites (108)

The Office of Franco Felizarta, MD

Bakersfield, California, 93301, United States

Location

Ruane Clinical Research Group Inc

Los Angeles, California, 90036, United States

Location

Southern California GI and Liver Center

San Clemente, California, 92673, United States

Location

Johns Hopkins Office of Capital Region Research - Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Washington University School Of Medicine

St Louis, Missouri, 63110, 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

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZA-SGS

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Fundacao de Medicina Tropical Doutor Heitor Vieira Dourado - FMT

Manaus, 69040-000, Brazil

Location

Universidade Federal da Bahia - Hospital Professor Edgard Santos

Salvador, 40110-060, Brazil

Location

Hospital Das Clinicas Da Faculdade De Medicina Da USP

São Paulo, 05403-000, Brazil

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

University of Alberta - Faculty of Medicine & Dentistry

Edmonton, Alberta, T6G 2G3, Canada

Location

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

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Vancouver ID Research and Care Centre Society

Vancouver, British Columbia, V6Z2C7, Canada

Location

Toronto General Hospital

Toronto, Ontario, ON M5G 2C4, Canada

Location

Nanfang Hospital

Guangzhou, 510515, China

Location

FN Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

RESEARCH SITE s.r.o.

Pilsen, 32600, Czechia

Location

KLIN MED s.r.o

Prague, 120 00, Czechia

Location

IKEM

Prague, 140 21, Czechia

Location

Hopital Beaujon

Clichy, 92110, France

Location

CHU de Grenoble Hopital Albert Michallon

Grenoble, 38043, France

Location

Hopital de La Croix Rousse

Lyon, 69004, France

Location

Hopital Saint Joseph

Marseille, 13008, France

Location

CHU de Nantes hotel Dieu

Nantes, 44093, France

Location

Hopital Saint-Antoine

Paris, 75012, France

Location

Chu Rennes Hopital Pontchaillou

Rennes, 35033, France

Location

Hopital Paul Brousse

Villejuif, 94800, France

Location

EPIMED GmbH

Berlin, 10787, Germany

Location

Universitatsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1

Frankfurt, 60590, Germany

Location

ICH Study Center GmbH & Co. KG

Hamburg, 20146, Germany

Location

University Medical Center

Hamburg, D-20246, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitatsmedizin der Johannes Gutenberg Universitat Mainz

Mainz, 55131, Germany

Location

The University of Hong Kong

Hong Kong, Hong Kong

Location

The Chinese University of Hong Kong

Shatin, Hong Kong

Location

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, 98124, Italy

Location

Irccs Ospedale Maggiore Di Milano

Milan, 20122, Italy

Location

Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara

Modena, 41126, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56124, Italy

Location

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

Rome, 00161, Italy

Location

Tokyo Medical and Dental University Hospital

Bunkyō City, 113 8519, Japan

Location

Chiba University Hospital

Chiba, 260 8677, Japan

Location

Fukui-ken Saiseikai Hospital

Fukui, 918-8503, Japan

Location

Fukuyama City Hospital

Fukuyama, 721-8511, Japan

Location

Hiroshima University Hospital

Hiroshima, 734 8551, Japan

Location

Kagawa Prefectural Central Hospital

Kagawa, 760-8557, Japan

Location

Nara Medical University Hospital

Kashihara, 634-8522, 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

The Hospital of Hyogo College of Medicine

Nishinomiya, 663-8501, Japan

Location

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

Osaka University Hospital

Suita-shi, 565-0871, Japan

Location

Toranomon Hospital

Tokyo, 105-8470, Japan

Location

Fujita Health University Hospital

Toyoake, 470-1192, Japan

Location

Hospital Sultanah Bahiyah

Alor Star, 05460, Malaysia

Location

Hospital Selayang

Batu Caves, 68100, Malaysia

Location

Hospital University Sains Malaysia

Kota Bharu, 16150, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy

Bydgoszcz, 85-030, Poland

Location

Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska

Gdansk, 80-462, Poland

Location

ID Clinic

Mysłowice, 41-400, Poland

Location

Wojewodzki Szpital Zakazny w Warszawie

Warsaw, 01-201, Poland

Location

SP ZOZ Wroclawskie Centrum Zdrowia

Wroclaw, 50-136, Poland

Location

Ural State Medical University

Chelyabinsk, 454092, Russia

Location

Krasnoyarsk Regional Center For AIDS And Infectious Diseases Treatment And Prophylaxis

Krasnoyarsk, 660049, Russia

Location

Clinic of the Modern Medicine

Moscow, 121170, Russia

Location

Medical Center SibNovoMed LLC

Novosibirsk, 630005, Russia

Location

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

Saint Petersburg, 190103, Russia

Location

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

Saint Petersburg, 195067, Russia

Location

Republican Clinical Infectious Hospital

Saint Petersburg, 196645, Russia

Location

Medical Company Hepatolog Ltd

Samara, 443063, Russia

Location

Smolensk Regional Clinical Hospital

Smolensk, 214018, Russia

Location

Stavropol State Medical University

Stavropol, 355017, Russia

Location

Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, 620102, Russia

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

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hosp Clinic de Barcelona

Barcelona, 08028, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 8035, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Puerta De Hierro

Madrid, 28222, Spain

Location

Hosp. Univ. Marques de Valdecilla

Santander, 39008, Spain

Location

Hosp. Gral. Univ. Valencia

Valencia, 46014, Spain

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

Hacettepe University Hospital

Ankara, 06230, Turkey (Türkiye)

Location

Ankara University Medical Faculty

Ankara, 06620, Turkey (Türkiye)

Location

Ankara Bilkent Sehir Hastanesi

Ankara, 6800, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Medical Faculty

Istanbul, 34098, 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

NHS Greater Glasgow and Clyde - Gartnavel General Hospital

Glasgow, G12 0YN, United Kingdom

Location

Grahame Hayton Unit

London, E1 1BB, United Kingdom

Location

Kings College Hospital

London, SE5 9RF, United Kingdom

Location

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

London, SW17 0RE, United Kingdom

Location

Related Publications (2)

• Verbinnen T, Lathouwers E, Jezorwski J, Biermer M, Augustyns I, Grant C, Agarwal K, Yuen MF, De Meyer S, Lenz O. Viral sequence analysis of chronic hepatitis B patients treated with the siRNA JNJ-73763989 in phase II clinical trials. JHEP Rep. 2025 Oct 9;7(12):101618. doi: 10.1016/j.jhepr.2025.101618. eCollection 2025 Dec.

  PMID: 41362713 DERIVED

• 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.

  PMID: 37442152 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

JNJ-56136379

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study 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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2019
• First Posted: June 11, 2019
• Study Start: August 1, 2019
• Primary Completion: March 29, 2021
• Study Completion: April 26, 2022
• Last Updated: February 4, 2025
• Results First Posted: July 10, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

BR (3); JP (15); DE (8); TU (6); CN (1); PL (5); MY (4); ES (6); CA (5); FR (8); BE (5); RU (11); KR (4); GB (4); US (8); TH (4); HK (2); IT (5); CZ (4)