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出境医 / 临床实验 / A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection (REEF-1)

A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection (REEF-1)

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Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis B, Chronic	Drug: JNJ-73763989 Drug: Placebo for JNJ-73763989 Drug: JNJ-56136379 Drug: Placebo for JNJ-56136379 Drug: Nucleos(t)ide Analog (NA)	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	471 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
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
Actual Study Start Date :	August 1, 2019
Actual Primary Completion Date :	March 29, 2021
Estimated Study Completion Date :	February 28, 2023

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: 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. Drug: JNJ-56136379 JNJ-56136379 tablets will be administered orally. Drug: Nucleos(t)ide Analog (NA) NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.
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.	Drug: 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. Drug: Placebo for JNJ-56136379 Placebo for JNJ-56136379 tablets will be administered orally. Drug: Nucleos(t)ide Analog (NA) NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.
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.	Drug: 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. Drug: Placebo for JNJ-56136379 Placebo for JNJ-56136379 tablets will be administered orally. Drug: Nucleos(t)ide Analog (NA) NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.
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.	Drug: 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. Drug: Placebo for JNJ-56136379 Placebo for JNJ-56136379 tablets will be administered orally. Drug: Nucleos(t)ide Analog (NA) NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.
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.	Drug: Placebo for JNJ-73763989 Placebo for JNJ-73763989 will be administered as subcutaneous injection. Drug: JNJ-56136379 JNJ-56136379 tablets will be administered orally. Drug: Nucleos(t)ide Analog (NA) NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.
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.	Drug: Placebo for JNJ-73763989 Placebo for JNJ-73763989 will be administered as subcutaneous injection. Drug: Placebo for JNJ-56136379 Placebo for JNJ-56136379 tablets will be administered orally. Drug: Nucleos(t)ide Analog (NA) NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.

Outcome Measures

Primary Outcome Measures :

Percentage of Participants Meeting the Nucleos(t)ide Analog (NA) Treatment Completion Criteria at Week 48 [ Time Frame: Week 48 ]
Percentage of participants meeting the NA treatment completion criteria at week 48 will be reported.

Secondary Outcome Measures :

Number of Participants with Adverse Events (AE) and Serious Adverse Events (SAE) as a Measure of Safety and Tolerability [ Time Frame: Up to follow-up (maximum up to 150 weeks) ]
An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants with Abnormalities in Clinical Laboratory Tests, 12-Lead Electrocardiogram (ECG), and Vital Signs [ Time Frame: Up to follow-up (maximum up to 150 weeks) ]
Number of participants with abnormalities in clinical laboratory tests, 12-lead ECG, and vital signs will be reported.
Percentage of Participants with HBsAg Seroclearance After Completion of all Study Intervention [ Time Frame: Week 72 and Week 96 ]
Percentage of participants with hepatitis B surface antigen (HBsAg) seroclearance after completion of all study intervention will be reported.
Percentage of Participants with HBV DNA less than (<) Lower Limit of Quantification (LLOQ) After Completion of all Study Intervention [ Time Frame: Week 72 and Week 96 ]
Percentage participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <LLOQ after completion of all study intervention will be reported.
Percentage of Participants Meeting the NA Treatment Completion Criteria During Follow-up [ Time Frame: Up to 96 weeks ]
Percentage of participants meeting the NA treatment completion criteria during follow-up will be reported.
Percentage of Participants with HBsAg Seroclearance After Completion of NA Treatment at any Time During Follow-up [ Time Frame: Up to 150 weeks ]
Percentage of participants with HBsAg seroclearance after completion of NA treatment at any time during follow-up will be reported.
Percentage of Participants Requiring NA Re-treatment During Follow-up [ Time Frame: Up to 150 weeks ]
Percentage of participants requiring NA re-treatment during follow-up will be reported.
Percentage of Participants with Relapse [ Time Frame: Up to 150 weeks ]
Percentage of participants with relapse will be reported.
Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance Considering Single and Multiple Markers [ Time Frame: Up to Week 96 ]
Percentage of participants with (sustained) reduction, suppression, and/or seroclearance considering single and multiple markers (such as hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], HBV DNA and alanine aminotransferase [ALT]) will be reported.
Percentage of Participants with HBsAg Seroconversion [ Time Frame: Up to 150 weeks ]
Percentage of participants with HBsAg seroconversion will be reported.
Percentage of Participants with HBeAg Seroconversion [ Time Frame: Up to 150 weeks ]
Percentage of participants with HBeAg seroconversion will be reported.
Change From Baseline in HBsAg Levels [ Time Frame: Baseline up to follow up (up to Week 150) ]
Change from baseline in HBsAg levels will be determined.
Change From Baseline in HBeAg Levels [ Time Frame: Baseline up to follow up (up to Week 150) ]
Change from baseline in HBeAg levels will be determined.
Change from Baseline in HBV DNA Levels [ Time Frame: Baseline up to follow up (up to Week 150) ]
Change from baseline in HBV DNA levels will be determined.
Time to Achieve HBsAg Seroclearance [ Time Frame: Up to Week 96 ]
Time to achieve HBsAg seroclearance will be determined.
Time to Achieve HBeAg Seroclearance [ Time Frame: Up to Week 96 ]
Time to achieve HBeAg seroclearance will be determined.
Percentage of Participants with <100 IU/mL or >1 log10 IU/mL Reduction in HBsAg From Baseline [ Time Frame: Baseline up to Week 150 ]
Percentage of participants with less than (<) 100 international units per milliliter (IU/mL) or greater than (>) 1 log10 IU/mL reduction in HBsAg from baseline will be assessed.
Percentage of HBeAg-positive Participants with HBeAg Levels [ Time Frame: Baseline up to Week 150 ]
Percentage of HBeAg-positive participants with HBeAg levels will be reported.
Percentage of Participants with ALT Decrease and Normalization [ Time Frame: Up to follow-up (maximum up to 150 weeks) ]
Percentage of participants with alanine aminotransferase (ALT) decrease and normalization will be reported.
Percentage of Participants with Virologic Breakthrough [ Time Frame: Up to Week 48 ]
Percentage of participants with virologic breakthrough defined as confirmed on-treatment HBV DNA increase by >1 log10 IU/mL from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below <LLOQ of the HBV DNA assay will be reported.
Percentage of Participants with Undetectable HBV DNA Levels After Re-start of NA Treatment During Follow-up [ Time Frame: Up to 150 weeks ]
Percentage of participants who reach HBV DNA undetectability after re-start of NA treatment during follow-up will be reported.
Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of JNJ-73763989 [ Time Frame: Days 1, 29, 85, 169 and 337 ]
The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.
Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of JNJ-56136379 [ Time Frame: Days 1, 29, 85, 169 and 337 ]
The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.
Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of NA [ Time Frame: Days 1, 29, 85, 169 and 337 ]
The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Locations

Show 108 study locations

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United States, California

The Office of Franco Felizarta, MD

Bakersfield, California, United States, 93301

Ruane Clinical Research Group Inc

Los Angeles, California, United States, 90036

Southern California GI and Liver Center

San Clemente, California, United States, 92673

United States, District of Columbia

Johns Hopkins Office of Capital Region Research - Sibley Memorial Hospital

Washington, District of Columbia, United States, 20016

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21287

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, New Jersey

I.D. Care, Inc.

Hillsborough, New Jersey, United States, 08844

United States, New York

NYU Hepatology Associates

New York, New York, United States, 10016

Belgium

SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)

Antwerpen, Belgium, 2060

Cliniques Universitaires Saint-Luc

Brussel, Belgium, 1200

UZ Antwerpen

Edegem, Belgium, 2650

Universitair Ziekenhuis Gent

Gent, Belgium, 9000

UZ Leuven

Leuven, Belgium, 3000

Brazil

Fundação De Medicina Tropical Doutor Heitor Vieira Dourado

Manaus, Brazil, 69040-000

Hospital das Clinicas da Universidade Federal da Bahia

Salvador, Brazil, 40110-060

Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo

Sao Paulo, Brazil, 05403-000

Canada, Alberta

University of Calgary

Calgary, Alberta, Canada, T2N 4Z6

University of Alberta - Faculty of Medicine & Dentistry

Edmonton, Alberta, Canada, T6G 2G3

Canada, British Columbia

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

Vancouver, British Columbia, Canada, V6Z 2K5

Vancouver ID Research and Care Centre Society

Vancouver, British Columbia, Canada, V6Z2C7

Canada

Toronto General Hospital

Toronto, Canada, ON M5G 2C4

China

Nanfang Hospital

Guangzhou, China, 510515

Czechia

FN Hradec Kralove

Hradec Kralove, Czechia, 500 05

RESEARCH SITE s.r.o.

Plzen, Czechia, 32600

KLIN MED s.r.o

Praha 2, Czechia, 120 00

IKEM

Praha, Czechia, 140 21

France

Hôpital Beaujon

Clichy, France, 92110

CHU de Grenoble - Hôpital Albert Michallon

Grenoble, France, 38043

Hopital de La Croix Rousse

Lyon, France, 69004

Hopital Saint Joseph

Marseille, France, 13008

CHU de Nantes hôtel-Dieu

Nantes, France, 44093

Hopital Saint-Antoine

Paris, France, 75012

Chu Rennes - Hopital Pontchaillou

Rennes, France, 35033

Hopital Paul Brousse

Villejuif, France, 94800

Germany

EPIMED GmbH

Berlin, Germany, 10787

Universitatsklinikum Essen

Essen, Germany, 45147

Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1

Frankfurt, Germany, 60590

ICH Study Center GmbH & Co. KG

Hamburg, Germany, 20146

University Medical Center

Hamburg, Germany, D-20246

Medizinische Hochschule Hannover

Hannover, Germany, 30625

Universitatsklinikum Leipzig

Leipzig, Germany, 04103

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, Germany, 55121

Hong Kong

The University of Hong Kong

Hong Kong, Hong Kong

The Chinese University of Hong Kong

Shatin, Hong Kong

Italy

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, Italy, 98124

Irccs Ospedale Maggiore Di Milano

Milano, Italy, 20122

Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara

Modena, Italy, 41126

Azienda Ospedaliero Universitaria Pisana

Pisa, Italy, 56124

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

Rome, Italy, 00161

Japan

Tokyo Medical and Dental University Medical Hospital

Bunkyo-ku, Japan, 113-8519

Chiba University Hospital

Chiba, Japan, 260-8677

Fukui-ken Saiseikai Hospital

Fukui City, Japan, 918-8503

Fukuyama City Hospital

Fukuyama, Japan, 721-8511

Hiroshima University Hospital

Hiroshima, Japan, 734-8551

Kagawa Prefectural Central Hospital

Kagawa, Japan, 760-8557

Nara Medical University Hospital

Kashihara, Japan, 634-8522

Musashino Red Cross Hospital

Musashino, Japan, 180-8610

National Hospital Organization Nagasaki Medical Center

Nagasaki, Japan, 856-8562

Nagoya City University Hospital

Nagoya, Japan, 467-8602

The Hospital of Hyogo College of Medicine

Nishinomiya, Japan, 663-8501

Hokkaido University Hospital

Sapporo-shi, Japan, 060-8648

Osaka University Hospital

Suita, Japan, 565-0871

Toranomon Hospital

Tokyo, Japan, 105-8470

Fujita Health University Hospital

Toyoake, Japan, 470-1192

Korea, Republic of

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 03722

Samsung Medical Center

Seoul, Korea, Republic of, 06351

Asan Medical Center

Seoul, Korea, Republic of, 5505

Malaysia

Hospital Sultanah Bahiyah

Alor Setar, Malaysia, 05460

Hospital Selayang

Batu Caves, Malaysia, 68100

Hospital University Sains Malaysia

Kota Bharu, Malaysia, 16150

University Malaya Medical Centre

Kuala Lumpur, Malaysia, 59120

Poland

Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy

Bydgoszcz, Poland, 85-030

Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska

Gdansk, Poland, 80-462

ID Clinic

Myslowice, Poland, 41-400

Wojewodzki Szpital Zakazny w Warszawie

Warszawa, Poland, 01-201

SP ZOZ Wroclawskie Centrum Zdrowia

Wroclaw, Poland, 50-136

Russian Federation

Ural State Medical University

Chelyabinsk, Russian Federation, 454092

Sverdlovsk Regional Clinical Hospital #1

Ekaterinburg, Russian Federation, 620102

Krasnoyarsk Regional Center For AIDS And Infectious Diseases Treatment And Prophylaxis

Krasnoyarsk, Russian Federation, 660049

Clinic of the Modern Medicine

Moscow, Russian Federation, 121170

Medical Center SibNovoMed LLC

Novosibirsk, Russian Federation, 630005

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

Saint Petersburg, Russian Federation, 190103

Republican Clinical Infectious Hospital

Saint Petersburg, Russian Federation, 196645

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

Saint-Petersburg, Russian Federation, 195067

Medical Company Hepatolog Ltd

Samara, Russian Federation, 443063

Smolensk Regional Clinical Hospital

Smolensk, Russian Federation, 214018

Stavropol State Medical University

Stavropol, Russian Federation, 355017

Spain

Hosp. Clinic I Provincial de Barcelona

Barcelona, Spain, 8028

Hosp. Univ. Vall D Hebron

Barcelona, Spain, 8035

Hosp. Univ. 12 de Octubre

Madrid, Spain, 28041

Hospital Puerta De Hierro

Madrid, Spain, 28222

Hosp. Univ. Marques de Valdecilla

Santander, Spain, 39008

Hosp. Gral. Univ. Valencia

Valencia, Spain, 46014

Thailand

King Chulalongkorn Memorial Hospital

Bangkok, Thailand, 10500

Siriraj Hospital

Bangkok, Thailand, 10700

Chiang Mai University Hospital

Chiang Mai, Thailand, 50200

Prince Of Songkla University

Songkla, Thailand, 90110

Turkey

Ankara University Medical Faculty

Ankara, Turkey, 06620

Hacettepe University Hospital

Ankara, Turkey, 6230

Ankara Sehir Hastanesi

Ankara, Turkey, 6800

Istanbul University Cerrahpasa Medical Faculty

Istanbul, Turkey, 34098

Ege University Medical of Faculty, Department of Gastroenterology

Izmir, Turkey, 35100

Karadeniz Teknik University Medical Faculty

Trabzon, Turkey, 61080

Tracking Information

First Submitted Date ^ICMJE

June 10, 2019

First Posted Date ^ICMJE

June 11, 2019

Last Update Posted Date

April 8, 2021

Actual Study Start Date ^ICMJE

August 1, 2019

Actual Primary Completion Date

March 29, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Percentage of Participants Meeting the Nucleos(t)ide Analog (NA) Treatment Completion Criteria at Week 48 [ Time Frame: Week 48 ]

Percentage of participants meeting the NA treatment completion criteria at week 48 will be reported.

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

Number of Participants with Adverse Events (AE) and Serious Adverse Events (SAE) as a Measure of Safety and Tolerability [ Time Frame: Up to follow-up (maximum up to 150 weeks) ]
An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants with Abnormalities in Clinical Laboratory Tests, 12-Lead Electrocardiogram (ECG), and Vital Signs [ Time Frame: Up to follow-up (maximum up to 150 weeks) ]
Number of participants with abnormalities in clinical laboratory tests, 12-lead ECG, and vital signs will be reported.
Percentage of Participants with HBsAg Seroclearance After Completion of all Study Intervention [ Time Frame: Week 72 and Week 96 ]
Percentage of participants with hepatitis B surface antigen (HBsAg) seroclearance after completion of all study intervention will be reported.
Percentage of Participants with HBV DNA less than (<) Lower Limit of Quantification (LLOQ) After Completion of all Study Intervention [ Time Frame: Week 72 and Week 96 ]
Percentage participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <LLOQ after completion of all study intervention will be reported.
Percentage of Participants Meeting the NA Treatment Completion Criteria During Follow-up [ Time Frame: Up to 96 weeks ]
Percentage of participants meeting the NA treatment completion criteria during follow-up will be reported.
Percentage of Participants with HBsAg Seroclearance After Completion of NA Treatment at any Time During Follow-up [ Time Frame: Up to 150 weeks ]
Percentage of participants with HBsAg seroclearance after completion of NA treatment at any time during follow-up will be reported.
Percentage of Participants Requiring NA Re-treatment During Follow-up [ Time Frame: Up to 150 weeks ]
Percentage of participants requiring NA re-treatment during follow-up will be reported.
Percentage of Participants with Relapse [ Time Frame: Up to 150 weeks ]
Percentage of participants with relapse will be reported.
Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance Considering Single and Multiple Markers [ Time Frame: Up to Week 96 ]
Percentage of participants with (sustained) reduction, suppression, and/or seroclearance considering single and multiple markers (such as hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], HBV DNA and alanine aminotransferase [ALT]) will be reported.
Percentage of Participants with HBsAg Seroconversion [ Time Frame: Up to 150 weeks ]
Percentage of participants with HBsAg seroconversion will be reported.
Percentage of Participants with HBeAg Seroconversion [ Time Frame: Up to 150 weeks ]
Percentage of participants with HBeAg seroconversion will be reported.
Change From Baseline in HBsAg Levels [ Time Frame: Baseline up to follow up (up to Week 150) ]
Change from baseline in HBsAg levels will be determined.
Change From Baseline in HBeAg Levels [ Time Frame: Baseline up to follow up (up to Week 150) ]
Change from baseline in HBeAg levels will be determined.
Change from Baseline in HBV DNA Levels [ Time Frame: Baseline up to follow up (up to Week 150) ]
Change from baseline in HBV DNA levels will be determined.
Time to Achieve HBsAg Seroclearance [ Time Frame: Up to Week 96 ]
Time to achieve HBsAg seroclearance will be determined.
Time to Achieve HBeAg Seroclearance [ Time Frame: Up to Week 96 ]
Time to achieve HBeAg seroclearance will be determined.
Percentage of Participants with <100 IU/mL or >1 log10 IU/mL Reduction in HBsAg From Baseline [ Time Frame: Baseline up to Week 150 ]
Percentage of participants with less than (<) 100 international units per milliliter (IU/mL) or greater than (>) 1 log10 IU/mL reduction in HBsAg from baseline will be assessed.
Percentage of HBeAg-positive Participants with HBeAg Levels [ Time Frame: Baseline up to Week 150 ]
Percentage of HBeAg-positive participants with HBeAg levels will be reported.
Percentage of Participants with ALT Decrease and Normalization [ Time Frame: Up to follow-up (maximum up to 150 weeks) ]
Percentage of participants with alanine aminotransferase (ALT) decrease and normalization will be reported.
Percentage of Participants with Virologic Breakthrough [ Time Frame: Up to Week 48 ]
Percentage of participants with virologic breakthrough defined as confirmed on-treatment HBV DNA increase by >1 log10 IU/mL from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below <LLOQ of the HBV DNA assay will be reported.
Percentage of Participants with Undetectable HBV DNA Levels After Re-start of NA Treatment During Follow-up [ Time Frame: Up to 150 weeks ]
Percentage of participants who reach HBV DNA undetectability after re-start of NA treatment during follow-up will be reported.
Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of JNJ-73763989 [ Time Frame: Days 1, 29, 85, 169 and 337 ]
The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.
Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of JNJ-56136379 [ Time Frame: Days 1, 29, 85, 169 and 337 ]
The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.
Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of NA [ Time Frame: Days 1, 29, 85, 169 and 337 ]
The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

Brief Summary

Detailed Description

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment

Condition ^ICMJE

Hepatitis B, Chronic

Intervention ^ICMJE

Drug: 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.
Drug: Placebo for JNJ-73763989
Placebo for JNJ-73763989 will be administered as subcutaneous injection.
Drug: JNJ-56136379
JNJ-56136379 tablets will be administered orally.
Drug: Placebo for JNJ-56136379
Placebo for JNJ-56136379 tablets will be administered orally.
Drug: Nucleos(t)ide Analog (NA)
NA treatment that is either of ETV, TDF or TAF tablets will be administered orally.

Study Arms ^ICMJE

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

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Active, not recruiting

Actual Enrollment ^ICMJE

471

Original Estimated Enrollment ^ICMJE

450

Estimated Study Completion Date ^ICMJE

February 28, 2023

Actual Primary Completion Date

March 29, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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)

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years to 65 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Belgium, Brazil, Canada, China, Czechia, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Malaysia, Poland, Russian Federation, Spain, Thailand, Turkey, United Kingdom, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT03982186

Other Study ID Numbers ^ICMJE

CR108608
2019-000622-22 ( EudraCT Number )
73763989HPB2001 ( Other Identifier: Janssen Sciences Ireland UC )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
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
URL:	https://www.janssen.com/clinical-trials/transparency

Responsible Party

Janssen Sciences Ireland UC

Study Sponsor ^ICMJE

Janssen Sciences Ireland UC

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Janssen Sciences Ireland UC Clinical Trial

Janssen Sciences Ireland UC

PRS Account

Janssen Sciences Ireland UC

Verification Date

April 2021

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

梅奥诊所
美国最佳医院荣誉榜第1名
克利夫兰诊所
美国最佳医院荣誉榜第2名
约翰霍普金斯医院
美国最佳医院荣誉榜第3名
麻省总医院
美国最佳医院荣誉榜第4名
密歇根大学医院
美国最佳医院荣誉榜第5名
倉敷中央医院
日本综合排名第1名
順天堂医院
日本综合排名第2名
藤田医科大学医院（原藤田保健大学医院)
日本综合排名第3名
北里大学医院
日本综合排名第4名
東京医科大学医院
日本综合排名第5名

4006 776 356

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A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection (REEF-1)

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