Clinical trial NCT03982186: A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Janssen Sciences Ireland UC
Sponsor class: INDUSTRY
First posted: 2019-06-11
Enrollment: 471
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Percentage of Participants Meeting the Nucleos(t)Ide Analog (NA) Treatment Completion Criteria at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Double-blind Phase: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Week 48
measure: Follow-up Phase 1: Percentage of Participants With TEAEs
timeFrame: From Week 48 up to Week 96
measure: Follow-up Phase 2: Percentage of Participants With TEAEs
timeFrame: From Week 48 up to Week 96
measure: Follow-up Phase 3: Percentage of Participants With TEAEs
timeFrame: From Week 48 up to Week 96
measure: Extended Follow-up Phase: Percentage of Participants With TEAEs
timeFrame: Extended Follow up Week 1 to extended follow up Week 48
measure: Double-blind Phase: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 48
measure: Follow-up Phase 1: Percentage of Participants With SAEs
timeFrame: From Week 48 up to Week 96
measure: Follow-up Phase 2: Percentage of Participants With SAEs
timeFrame: From Week 48 up to Week 96
measure: Follow-up Phase 3: Percentage of Participants With SAEs
timeFrame: From Week 48 up to Week 96
measure: Extended Follow-up Phase: Percentage of Participants With SAEs
timeFrame: Extended Follow up Week 1 to extended follow up Week 48
measure: Percentage of Participants With Abnormalities in Clinical Laboratory Tests (Hematology)
timeFrame: Double blind (DB) phase: Baseline (Day 1) up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
measure: Percentage of Participants With Abnormalities in Clinical Laboratory Tests (Chemistry)
timeFrame: Double blind (DB) phase: Baseline up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
measure: Percentage of Participants With Abnormalities in Clinical Laboratory Tests (Urinalysis)
timeFrame: Double blind (DB) phase: Baseline up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
measure: Percentage of Participants With Abnormalities in Electrocardiogram (ECG)
timeFrame: Double blind (DB) phase: Baseline (Day 1) up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
measure: Percentage of Participants With Abnormalities in Vital Signs
timeFrame: Double blind (DB) phase: Baseline (Day 1) up to Week 48, Follow up (FU) phase: Week 48 up to Week 96
measure: Percentage of Participants With HBsAg Seroclearance 24 Weeks After Completion of All Study Intervention at Week 48
timeFrame: Week 72
measure: Percentage of Participants With HBsAg Seroclearance 48 Weeks After Completion of All Study Intervention at Week 48
timeFrame: Week 96
measure: Percentage of Participants With HBV DNA <LLOQ 24 and 48 Weeks After Completion of All Study Intervention at Week 48
timeFrame: Weeks 72 and 96
measure: Percentage of Participants Meeting the NA Treatment Completion Criteria During Follow-up
timeFrame: Week 48 up to Week 96
measure: Percentage of Participants With HBsAg Seroclearance After Completion of NA Treatment at Weeks 60, 84, and 96
timeFrame: Weeks 60, 84, and 96
measure: Percentage of Participants Who Required NA Re-treatment During Follow-up
timeFrame: Week 48 up to Week 96
measure: Percentage of Participants With Flares
timeFrame: Follow-up phase (Week 48 up to Week 96)
measure: Number of Participants With (Sustained) Reduction, Suppression, and/or Seroclearance Considering Single and Multiple Marker
timeFrame: Weeks 12, 24, 36 and 48
measure: Percentage of Participants With HBsAg Seroconversion
timeFrame: Weeks 48, 60, 72, and 96
measure: Percentage of Participants With HBeAg Seroconversion
timeFrame: Weeks 48, 60, 72, and 96
measure: Change From Baseline in HBsAg Levels
timeFrame: Baseline, Weeks 12, 24, 48, 60, 72, 96
measure: Change From Baseline in HBeAg Levels
timeFrame: Baseline, Weeks 12, 24, 48, 60, 72, 96
measure: Change From Baseline in HBV DNA Levels
timeFrame: Baseline, Weeks 12, 24, 48, 60, 72, 96
measure: Time to Achieve HBsAg Seroclearance
timeFrame: Baseline (Day 1) up to Week 96
measure: Time to Achieve HBeAg Seroclearance
timeFrame: Baseline (Day 1) up to Week 96
measure: Percentage of Participants With HBsAg Levels <100 IU/mL
timeFrame: Baseline, Weeks 12, 24, 48, 60, 72, 96
measure: Percentage of Participants With HBsAg Levels >1 log10 IU/mL Reduction From Baseline
timeFrame: Weeks 12, 24, 48, 60, 72, 96
measure: Percentage of HBeAg-positive Participants With HBeAg Levels <LLOQ
timeFrame: Weeks 12, 24, 48, 60, 72, 96
measure: Percentage of HBeAg-positive Participants With HBeAg Levels >1 log10 IU/mL
timeFrame: Weeks 12, 24, 48, 60, 72, 96
measure: Percentage of Participants With HBV DNA Levels <LLOQ
timeFrame: Baseline, Weeks 12, 24, 48, 60, 72, 96
measure: Mean Change From Baseline in ALT at EOT (Week 48) in Participants With Elevated ALT at Baseline
timeFrame: Baseline and Week 48
measure: Percentage of Participants With ALT Normalization
timeFrame: Baseline, Weeks 12, 24, 48, 60, 72, 96
measure: Percentage of Participants With Virologic Breakthrough
timeFrame: Baseline (Day 1) up to Week 48
measure: Percentage of Participants With Undetectable HBV DNA Levels After Re-start of NA Treatment During Follow-up
timeFrame: Week 48 up to Week 96
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: The Office of Franco Felizarta, MD
state: California
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group Inc
state: California
city: San Clemente
country: United States
facility: Southern California GI and Liver Center
state: California
city: Washington
country: United States
facility: Johns Hopkins Office of Capital Region Research - Sibley Memorial Hospital
state: District of Columbia
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Hillsborough
country: United States
facility: I.D. Care, Inc.
state: New Jersey
city: New York
country: United States
facility: NYU Hepatology Associates
state: New York
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Edegem
country: Belgium
facility: UZA-SGS
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Manaus
country: Brazil
facility: Fundacao de Medicina Tropical Doutor Heitor Vieira Dourado - FMT
city: Salvador
country: Brazil
facility: Universidade Federal da Bahia - Hospital Professor Edgard Santos
city: Sao Paulo
country: Brazil
facility: Hospital Das Clinicas Da Faculdade De Medicina Da USP
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta - Faculty of Medicine & Dentistry
state: Alberta
city: Vancouver
country: Canada
facility: GI Research Institute (G.I.R.I.)
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver ID Research and Care Centre Society
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Guangzhou
country: China
facility: Nanfang Hospital
city: Hradec Kralove
country: Czechia
facility: FN Hradec Kralove
city: Plzen
country: Czechia
facility: RESEARCH SITE s.r.o.
city: Praha 2
country: Czechia
facility: KLIN MED s.r.o
city: Praha
country: Czechia
facility: IKEM
city: Clichy
country: France
facility: Hopital Beaujon
city: Grenoble
country: France
facility: CHU de Grenoble Hopital Albert Michallon
city: Lyon
country: France
facility: Hopital de La Croix Rousse
city: Marseille
country: France
facility: Hopital Saint Joseph
city: Nantes
country: France
facility: CHU de Nantes hotel Dieu
city: Paris
country: France
facility: Hopital Saint-Antoine
city: Rennes
country: France
facility: Chu Rennes Hopital Pontchaillou
city: Villejuif
country: France
facility: Hopital Paul Brousse
city: Berlin
country: Germany
facility: EPIMED GmbH
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Frankfurt
country: Germany
facility: Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
city: Hamburg
country: Germany
facility: ICH Study Center GmbH & Co. KG
city: Hamburg
country: Germany
facility: University Medical Center
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Mainz
country: Germany
facility: Universitatsmedizin der Johannes Gutenberg Universitat Mainz
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
city: Shatin
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico G. Martino
city: Milano
country: Italy
facility: Irccs Ospedale Maggiore Di Milano
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Rome
country: Italy
facility: Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma
city: Bunkyo Ku
country: Japan
facility: Tokyo Medical and Dental University Hospital
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Fukui City
country: Japan
facility: Fukui-ken Saiseikai Hospital
city: Fukuyama
country: Japan
facility: Fukuyama City Hospital
city: Hiroshima shi
country: Japan
facility: Hiroshima University Hospital
city: Kagawa
country: Japan
facility: Kagawa Prefectural Central Hospital
city: Kashihara
country: Japan
facility: Nara Medical University Hospital
city: Musashino
country: Japan
facility: Musashino Red Cross Hospital
city: Nagasaki
country: Japan
facility: National Hospital Organization Nagasaki Medical Center
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Nishinomiya
country: Japan
facility: The Hospital of Hyogo College of Medicine
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
city: Suita-shi
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: Toranomon Hospital
city: Toyoake
country: Japan
facility: Fujita Health University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Alor Setar
country: Malaysia
facility: Hospital Sultanah Bahiyah
city: Batu Caves
country: Malaysia
facility: Hospital Selayang
city: Kota Bharu
country: Malaysia
facility: Hospital University Sains Malaysia
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy
city: Gdansk
country: Poland
facility: Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska
city: Myslowice
country: Poland
facility: ID Clinic
city: Warszawa
country: Poland
facility: Wojewodzki Szpital Zakazny w Warszawie
city: Wroclaw
country: Poland
facility: SP ZOZ Wroclawskie Centrum Zdrowia
city: Chelyabinsk
country: Russian Federation
facility: Ural State Medical University
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Clinical Hospital #1
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Center For AIDS And Infectious Diseases Treatment And Prophylaxis
city: Moscow
country: Russian Federation
facility: Clinic of the Modern Medicine
city: Novosibirsk
country: Russian Federation
facility: Medical Center SibNovoMed LLC
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis
city: Saint Petersburg
country: Russian Federation
facility: Republican Clinical Infectious Hospital
city: Saint-Petersburg
country: Russian Federation
facility: Clinical Infectious Diseases Hospital n. a. S.P. Botkin
city: Samara
country: Russian Federation
facility: Medical Company Hepatolog Ltd
city: Smolensk
country: Russian Federation
facility: Smolensk Regional Clinical Hospital
city: Stavropol
country: Russian Federation
facility: Stavropol State Medical University
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Puerta De Hierro
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Valencia
country: Spain
facility: Hosp. Gral. Univ. Valencia
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai University Hospital
city: Songkla
country: Thailand
facility: Prince Of Songkla University
city: Ankara
country: Turkey
facility: Hacettepe University Hospital
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Ankara
country: Turkey
facility: Ankara Bilkent Sehir Hastanesi
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Izmir
country: Turkey
facility: Ege University Medical of Faculty, Department of Gastroenterology
city: Trabzon
country: Turkey
facility: Karadeniz Teknik University Medical Faculty
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde - Gartnavel General Hospital
city: London
country: United Kingdom
facility: Grahame Hayton Unit
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: St Georges University of London and St George's University Hospitals NHS Foundation Trust
Study officials:
affiliation: Janssen Sciences Ireland UC
name: Janssen Sciences Ireland UC Clinical Trial
role: STUDY_DIRECTOR
References: