An Efficacy, Safety, and Pharmacokinetics Study of JNJ-56136379 in Participants With Chronic Hepatitis B Virus Infection
- Conditions
- Hepatitis B
- Interventions
- Registration Number
- NCT03361956
- Lead Sponsor
- Janssen Sciences Ireland UC
- Brief Summary
The main purpose of this study is to evaluate efficacy of 24 weeks of study treatment, in terms of changes in hepatitis B surface antigen (HBsAg) levels.
- Detailed Description
The main study consists of 2-parts and each part will consist of 2 types of Chronic Hepatitis B-infected participant populations. Each part of the study will consist of screening phase (up to 8 weeks), treatment phase (24 weeks or 48 weeks, depending on treatment response), and post-treatment follow-up phase (24 weeks or 48 weeks, depending on treatment response). The duration of individual participation will be up to approximately 56 weeks (participants not eligible to continue treatment in extension phase), up to 80 weeks (participants continuing treatment in extension phase but not meeting treatment completion criteria), or up to 104 weeks (participants meeting treatment completion criteria). The safety and efficacy will be monitored throughout the study. In a separate substudy, at selected clinical sites, percutaneous core liver biopsy will be performed to evaluate changes of intrahepatic viral parameters.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 232
- Participants must have a body mass index (weight in kilogram (kg) divided by the square of height in meters) of 18.0 to 35.0 kilogram / square meter (kg/m^2), extremes included
- Participants must have chronic hepatitis B virus infection (CHB) infection documented by: Serum hepatitis B surface antigen (HBsAg)-positive at screening and serum HBsAg- or hepatitis B virus (HBV) deoxyribonucleic acid (DNA)-positive at least 6 months prior to screening; Serum immunoglobulin M (IgM) anti- hepatitis B core-related (HBc) antibody negative at screening
- In participants currently not being treated (Treatment Arms 1-2-3 and 6-7-8): Participants must not be receiving any CHB treatment at screening, that is, Have never received treatment with HBV antiviral medicines, including NAs or interferon (IFN) products, OR Have not been on treatment with HBV antiviral medicines, including nucleos(t)ide analog (NA)s or IFN products within 6 months prior to baseline (first intake of study drugs), and participants must be HBeAg-positive and have HBV DNA greater than or equal to (>=) 20,000 International Units Per Milliliter (IU/mL), OR be hepatitis B e antigen (HBeAg)-negative and have HBV DNA >=2,000 IU /mL at screening, and participants must have HBsAg greater than (>) 250 IU/mL at screening, and participants must have alanine aminotransferase (ALT) > upper limit of normal (ULN) and less than or equal to (<=) 5 * ULN at screening, determined in the central laboratory
- In virologically suppressed participants (Treatment Arms 4-5 and 9-10): Participants must be virologically suppressed by current NA treatment (entecavir (ETV) or tenofovir disoproxil fumarate (TDF)) as defined by HBV DNA less than (<) 60 IU/mL at screening and at least 6 months prior to screening, and participants must be on the same NA treatment (ETV or TDF) and the same dose for >=12 months prior to screening, and participants must have HBsAg > 250 IU/mL at screening, and participants must have ALT <=2*ULN at screening
- Participants must have: A liver biopsy result classified as Metavir F0-F2 within 1 year prior to screening or at the time of screening, OR FibroScan liver stiffness measurement <8.0 kilopascal (kPa) within 6 months prior to screening or at the time of screening
Main Study:
- Participants who test positive for anti-hepatitis B surface (HBs) antibodies
- Participants with current hepatitis A virus infection (confirmed by hepatitis A antibody immunoglobulin M [IgM]), hepatitis D virus (HDV) infection (confirmed by HDV antibody), hepatitis E virus infection (confirmed by hepatitis E antibody IgM), or human immunodeficiency virus (HIV)-1 or HIV-2 infection (confirmed by antibodies) at screening; participants with a history of or current HCV infection (confirmed by HCV antibody). Evidence of other active infection (bacterial, viral, fungal, including acute tuberculosis) deemed clinically relevant by the investigator that would interfere with study conduct or its interpretation will also lead to exclusion
- Participants with any evidence of hepatic decompensation at any time point prior to or at the time of screening: Direct bilirubin >1.2* ULN, or International normalized ratio (INR) >1.5* ULN, or Serum albumin < lower limit of normal (LLN), or documented history or current evidence of variceal bleeding, ascites, or hepatic encephalopathy
- Participants with a history of cardiac arrhythmia (example, extrasystoli, tachycardia at rest), history of risk factors for Torsades de Pointes syndrome (example, hypokalemia, family history of long QT syndrome) or history or other clinical evidence of significant or unstable cardiac disease (example, angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease, and/or clinically significant 12 lead electrocardiograms (ECGs) abnormalities), moderate to severe valvular disease, or uncontrolled hypertension at screening
- Participants with contraindications to the use of ETV or TDF per local prescribing information
Substudy:
- Presence of coagulopathy or hemoglobinopathy (including sickle cell disease, thalassemia)
- Use of any anti-coagulant, anti-platelet, or non-steroidal anti-inflammatory drug medications from 10 days before until 5 days after each liver biopsy
- Presence of ascites, focal liver lesions, and other findings that would be contraindications for liver biopsies
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Arm 1 (JNJ-56136379 or NA) (open label) JNJ-56136379 Participants with hepatitis B virus (HBV) currently not being treated and receiving JNJ-56136379 tablet (at a lower dose) orally for 24 weeks, will stop further dosing with JNJ-56136379 and start treatment with nucleos(t)ide analog (NA) (entecavir \[ETV\] or tenofovir disoproxil fumarate \[TDF\]), and enter the 24 week post treatment follow-up phase. Part A: Arm 1 (JNJ-56136379 or NA) (open label) NA (ETV or TDF) Participants with hepatitis B virus (HBV) currently not being treated and receiving JNJ-56136379 tablet (at a lower dose) orally for 24 weeks, will stop further dosing with JNJ-56136379 and start treatment with nucleos(t)ide analog (NA) (entecavir \[ETV\] or tenofovir disoproxil fumarate \[TDF\]), and enter the 24 week post treatment follow-up phase. Part A: Arm 2 (Placebo+NA [ETV] or [TDF]) Placebo Participants with HBV currently not being treated will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part A: Arm 3 (JNJ-56136379 + NA [ETV or TDF]) JNJ-56136379 Participants with HBV currently not being treated will receive JNJ-56136379 along with NA (ETV or TDF) tablet orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part B: Arm 8 (JNJ-56136379 + NA [ETV or TDF]) JNJ-56136379 Participants with HBV currently not being treated will receive JNJ-56136379 tablet at a high dose along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part B: Arm 9 (placebo + NA [ETV or TDF]) Placebo Virologically suppressed participants will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part B: Arm 9 (placebo + NA [ETV or TDF]) NA (ETV or TDF) Virologically suppressed participants will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part B: Arm 10 (JNJ-56136379 + NA [ETV or TDF]) JNJ-56136379 Virologically suppressed participants will receive JNJ-56136379 tablet at a high dose along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part B: Arm 10 (JNJ-56136379 + NA [ETV or TDF]) NA (ETV or TDF) Virologically suppressed participants will receive JNJ-56136379 tablet at a high dose along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part A: Arm 4 (Placebo + NA [ETV or TDF]) Placebo Virologically suppressed participants will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part A: Arm 5 (JNJ-56136379 + NA [ETV or TDF]) JNJ-56136379 Virologically suppressed participants will receive JNJ-56136379 along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part A: Arm 5 (JNJ-56136379 + NA [ETV or TDF]) NA (ETV or TDF) Virologically suppressed participants will receive JNJ-56136379 along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part B: Arm 6 (JNJ-56136379 + NA [ETV or TDF]) (open label) JNJ-56136379 Participants with HBV currently not being treated will receive JNJ-56136379 tablet at a high dose, orally for 24 weeks. The eligible participants may enter the extension phase and will receive JNJ-56136379 along with NA (ETV or TDF) from Week 24 to Week 48. Part B: Arm 7 (placebo + NA [ETV or TDF]) Placebo Participants with HBV currently not being treated will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part A: Arm 4 (Placebo + NA [ETV or TDF]) NA (ETV or TDF) Virologically suppressed participants will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part A: Arm 2 (Placebo+NA [ETV] or [TDF]) NA (ETV or TDF) Participants with HBV currently not being treated will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part A: Arm 3 (JNJ-56136379 + NA [ETV or TDF]) NA (ETV or TDF) Participants with HBV currently not being treated will receive JNJ-56136379 along with NA (ETV or TDF) tablet orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part B: Arm 6 (JNJ-56136379 + NA [ETV or TDF]) (open label) NA (ETV or TDF) Participants with HBV currently not being treated will receive JNJ-56136379 tablet at a high dose, orally for 24 weeks. The eligible participants may enter the extension phase and will receive JNJ-56136379 along with NA (ETV or TDF) from Week 24 to Week 48. Part B: Arm 7 (placebo + NA [ETV or TDF]) NA (ETV or TDF) Participants with HBV currently not being treated will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks. Part B: Arm 8 (JNJ-56136379 + NA [ETV or TDF]) NA (ETV or TDF) Participants with HBV currently not being treated will receive JNJ-56136379 tablet at a high dose along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels in Currently Not Treated Population at Week 24 Baseline and Week 24 Change from baseline in HBsAg levels in currently not treated population at Week 24 based on Hepatitis B e Antigen (HBeAg) status was reported. Currently not treated population defined as participants who didn't receive any hepatitis B virus (HBV) treatment 6 months prior to baseline.
Change From Baseline in HBsAg Levels in Virologically Suppressed Population at Week 24 Baseline and Week 24 Change from baseline in HBsAg levels in virologically suppressed population at Week 24 based on HBeAg status was reported. Virologically suppressed population defined as participants who were on entecavir (ETV) or tenofovir disoproxil fumarate (TDF) for at least 12 months prior to screening and had HBV deoxyribonucleic acid (DNA) \<60 IU/mL. This outcome measure was planned to be analyzed for specified arms only.
- Secondary Outcome Measures
Name Time Method Change From Baseline in HBsAg Levels in Virologically Suppressed Population Over Time Weeks 24, 48 and Follow-up Week 24 Change from baseline in HBsAg levels in virologically suppressed population based on HBeAg status was reported. This outcome measure was planned to be analyzed for specified arms only.
Change From Baseline in HBV DNA Levels in Virologically Suppressed Population Baseline up to Weeks 24, 48 and Follow-up Week 24 Change from baseline in HBV DNA levels in virologically supressed population based on their HBeAg status was reported. This outcome measure was planned to be analyzed for specified arms only.
Percentage of Participants With Undetectable HBV DNA Levels in Currently Not Treated Population Weeks 24, 48 and Follow-up Week 24 Percentage of participants with undetectable HBV DNA levels in currently not treated population based on their HBeAg status was evaluated.
Percentage of Participants With HBsAg Seroclearance in Currently Not Treated Population Weeks 24 and 48 Percentage of participants with HBsAg seroclearance in currently not treated population based on their HBeAg status were reported. Seroclearance at Week 24/48 of the treatment defined as a confirmed loss of HBsAg at Week 24/48. Loss is defined as a baseline HBsAg with a repeat reactive, confirmed or positive result and a post-baseline assessment with a negative result. This outcome measure was planned to be analyzed at specified timepoints only.
Percentage of Participants With HBsAg Seroclearance in Virologically Suppressed Population Weeks 24 and 48 Percentage of participants with HBsAg seroclearance in virologically suppressed population based on their HBeAg status were reported. Seroclearance at Week 24/48 of the treatment defined as a confirmed loss of HBsAg at Week 24/48. Loss is defined as a baseline HBsAg with a repeat reactive, confirmed or positive result and a post-baseline assessment with a negative result. This outcome measure was planned to be analyzed for specified arms and specific timepoints only .
Percentage of Participants With Normalized Alanine Aminotransferase (ALT) Levels in Currently Not Treated Population Weeks 24, 48 and Follow-up Week 24 Percentage of participants with normalized ALT levels in currently not treated population, whose ALT levels were above upper limit of normal at baseline based on their HBeAg status were reported.
Percentage of Participants With Normalized ALT Levels in Virologically Suppressed Population Weeks 24, 48 and Follow-up Week 24 Percentage of participants with normalized ALT levels in virologically suppressed population, whose ALT levels were above upper limit of normal at baseline based on their HBeAg status were reported. This outcome measure was planned to be analyzed for specified arms only.
Percentage of Participants With Virological Breakthrough in Virologically Suppressed Population Weeks 24 and 48 Percentage of participants with virological breakthrough in virologically suppressed population based on their HBeAg status was reported. Virological breakthrough defined as confirmed on treatment HBV DNA increase by \>1 log10 from nadir level or confirmed on treatment level \>200 IU/mL in participants who had HBV DNA level below the lower limit of quantification (LLOQ) of the HBV DNA assay. This outcome measure was planned to be analyzed for specified arms only.
Number of Participants With Serious Adverse Events (SAEs) Up to Week 80 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.
Percentage of Participants With >0.5 log10 IU/mL or >1 log10 IU/mL Reduction in HBsAg From Baseline in Virologically Suppressed Population Weeks 24, 48 and Follow-up Week 24 Percentage of participants with \>0.5 log10 IU/mL or \>1 log10 IU/mL reduction in HBsAg from baseline in virologically suppressed population based on their HBeAg status were reported. This outcome measure was planned to be analyzed for specified arms only.
Change From Baseline in HBeAg Levels in Virologically Suppressed Population Baseline up to Weeks 24, 48 and Follow-up Week 24 Change from baseline in HBeAg levels in HBeAg positive virologically suppressed population was reported. This outcome measure was planned to be analyzed for specified arms only.
Percentage of Participants With >0.5 log10 IU/mL and >1 log10 IU/mL Reduction in HBeAg From Baseline in Virologically Suppressed Population Weeks 24, 48 and Follow-up Week 24 Percentage of participants with \>0.5 log10 IU/mL and \>1 log10 IU/mL reduction in HBeAg from baseline in HBeAg positive virologically suppressed population was reported. This outcome measure was planned to be analyzed for specified arms only.
Plasma Concentrations of ETV in Virologically Suppressed Population Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4 Plasma concentrations of ETV administered as monotherapy or co-administered with JNJ-56136379 in virologically suppressed population was determined. As planned, plasma concentration of ETV co-administered with placebo was analyzed separately for Part A and Part B. Samples were analyzed using POP PK modeling.
Plasma Concentrations of JNJ-56136379 in Currently Not Treated Population Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4 Plasma concentrations of JNJ-56136379 in currently not treated population administered as monotherapy or when co-administered with NA (ETV or TDF) was determined. As planned, the plasma concentration of JNJ-56136379 when co-administered with NA was determined separately for each NA treatment (ETV and TDF). Samples were analyzed using POP PK modeling.
Number of Participants With Treatment- Emergent Adverse Events (AEs) Up to Week 48 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. Treatment-emergent AEs were AEs with onset during the treatment phase or that worsened since baseline.
Percentage of Participants With HBsAg Levels <1,000 or <100 IU/mL in Virologically Suppressed Population Weeks 24, 48 and Follow-up Week 24 Percentage of participants with HBsAg levels \<1,000 or \<100 IU/mL in virologically suppressed population based on their HBeAg status were reported. This outcome measure was planned to be analyzed for specified arms only.
Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels in Currently Not Treated Population Baseline up to Weeks 24, 48 and Follow-up Week 24 Change from baseline in HBV DNA levels in currently not treated population based on their HBeAg status was reported.
Change From Baseline in HBeAg Levels in Currently Not Treated Population Baseline up to Weeks 24, 48 and Follow-up Week 24 Change from baseline in HBeAg levels in HBeAg positive currently not treated population was reported.
Percentage of Participants With HBsAg Seroconversion in Currently Not Treated Population Weeks 24 and 48 Percentage of participants with HBsAg seroconversion in currently not treated population based on their HBeAg status were reported. Seroconversion at Week 24/48 of the treatment defined as a confirmed loss of HBsAg at week 24/48 of the treatment and an appearance of Anti-HBs. This outcome measure was planned to be analyzed for specified timepoints only.
Percentage of Participants With HBsAg Seroconversion in Virologically Suppressed Population Weeks 24 and 48 Percentage of participants with HBsAg seroconversion in virologically suppressed population based on their HBeAg status were reported. Seroconversion at Week 24/48 of the treatment defined as a confirmed loss of HBsAg at week 24/48 of the treatment and an appearance of Anti-HBs. This outcome measure was planned to be analyzed for specified arms and specified timepoints only.
Plasma Concentrations of TDF in Virologically Suppressed Population Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4 Plasma concentrations of TDF administered as monotherapy or co-administered with JNJ-56136379 was determined. As planned, plasma concentration of TDF co-administered with placebo was analyzed separately for Part A and Part B. Samples were analyzed using POP PK modeling.
Number of Participants With Clinically Significant Changes in Vital Signs, Physical Examinations, Electrocardiogram (ECG), and Clinical Laboratory Tests Up to Week 80 Number of participants with clinically significant changes in vital signs, physical examinations, ECG, and clinical laboratory tests (including hematology, blood biochemistry, blood coagulation, and urinalysis) were reported.
Change From Baseline in HBsAg Levels in Currently Not Treated Population Over Time Weeks 24, 48 and Follow-up Week 24 Change from baseline in HBsAg levels in currently not treated population based on HBeAg status was reported.
Plasma Concentrations of JNJ-56136379 in Virologically Suppressed Population Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4 Plasma concentrations of JNJ-56136379 in virologically suppressed population administered as monotherapy or when co-administered with NA (ETV or TDF) was determined. As planned, the plasma concentration of JNJ-56136379 when co-administered with NA was determined separately for each NA treatment (ETV and TDF). Samples were analyzed using POP PK modeling.
Number of Participants With Treatment-Associated Mutations From Week 0 to Week 24, From Week 25 to Week 48, Up to Follow-up Week 24 Number of participants with treatment-associated mutations were reported. Viral genome sequence analysis was performed to evaluate emergence of mutations associated with JNJ-56136379 considering 15 HBV core protein positions of interest. This outcome measure was planned to be analyzed for specified arms only.
Percentage of Participants With HBsAg Levels Less Than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) in Currently Not Treated Population Weeks 24, 48 and Follow-up Week 24 Percentage of participants with HBsAg levels \<1,000 or \<100 IU/mL in currently not treated population based on their HBeAg status were reported.
Percentage of Participants With Greater Than (>) 0.5 log10 IU/mL or >1 log10 IU/mL Reduction in HBsAg From Baseline in Currently Not Treated Population Weeks 24, 48 and Follow-up Week 24 Percentage of participants with \>0.5 log10 IU/mL or \>1 log10 IU/mL reduction in HBsAg from baseline in currently not treated population based on their HBeAg status were reported.
Percentage of Participants With Undetectable HBV DNA Levels in Virologically Suppressed Population Weeks 24, 48 and Follow-up Week 24 Percentage of participants with undetectable HBV DNA levels in virologically suppressed population based on their HBeAg status were reported. This outcome measure was planned to be analyzed for specified arms only.
Percentage of Participants With >0.5 log10 IU/mL and >1 log10 IU/mL Reduction in HBeAg From Baseline in Currently Not Treated Population Weeks 24, 48 and Follow-up Week 24 Percentage of participants with \>0.5 log10 IU/mL and \>1 log10 IU/mL reduction in HBeAg from baseline in HBeAg positive currently not treated population was reported.
Percentage of Participants With Virological Breakthrough in Currently Not Treated Population Weeks 24 and 48 Percentage of participants with virological breakthrough in currently not treated population based on their HBeAg status was reported. Virological breakthrough defined as confirmed on treatment HBV DNA increase by \>1 log10 from nadir level or confirmed on treatment level \>200 IU/mL in participants who had HBV DNA level below the lower limit of quantification (LLOQ) of the HBV DNA assay.
Plasma Concentrations of Entecavir [ETV] in Currently Not Treated Population Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4 Plasma concentrations of ETV administered as monotherapy or co-administered with JNJ-56136379 in currently not treated population was determined. As planned, plasma concentration of ETV co-administered with placebo was analyzed separately for Part A and Part B. Samples were analyzed using POP PK modeling.
Plasma Concentrations of Tenofovir Disoproxil Fumarate (TDF) in Currently Not Treated Population Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4 Plasma concentrations of TDF administered as monotherapy or co-administered with JNJ-56136379 was determined. As planned, plasma concentration of TDF co-administered with placebo was analyzed separately for Part A and Part B. Samples were analyzed using POP PK modeling.
Trial Locations
- Locations (76)
Queen Mary Hospital, University of Hong Kong
ðŸ‡ðŸ‡°Hong Kong, Hong Kong
Musashino Red Cross Hospital
🇯🇵Musashino, Japan
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
🇩🇪Frankfurt, Germany
The Office of Franco Felizarta, MD
🇺🇸Bakersfield, California, United States
NYU Hepatology Associates
🇺🇸New York, New York, United States
Tulane Medical Center (TMC)
🇺🇸New Orleans, Louisiana, United States
UPMC Center For Liver Diseases
🇺🇸Pittsburgh, Pennsylvania, United States
The First Hospital of Jilin University
🇨🇳Changchun, China
Peking University People's Hospital
🇨🇳Beijing, China
Nagoya City University Hospital
🇯🇵Nagoya, Japan
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)
🇧🇪Antwerpen, Belgium
I.D. Care, Inc.
🇺🇸Hillsborough, New Jersey, United States
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Toronto General Hospital
🇨🇦Toronto, Canada
Hosp. Clinic I Provincial de Barcelona
🇪🇸Barcelona, Spain
Hosp. Univ. Vall D Hebron
🇪🇸Barcelona, Spain
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Medical Center SibNovoMed LLC
🇷🇺Novosibirsk, Russian Federation
Medical Company Hepatolog Ltd
🇷🇺Samara, Russian Federation
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Irccs Ospedale Maggiore Di Milano
🇮🇹Milano, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Stavropol State Medical University
🇷🇺Stavropol, Russian Federation
Hosp. Univ. Marques de Valdecilla
🇪🇸Santander, Spain
Wojewodzki Szpital Zespolony
🇵🇱Kielce, Poland
Siriraj Hospital
🇹ðŸ‡Bangkok, Thailand
Istanbul University Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Hosp. Univ. Ramon Y Cajal
🇪🇸Madrid, Spain
SE 'National institute therapy named L.T. Maloi NAMS of Ukraine'
🇺🇦Kharkiv, Ukraine
Chiang Mai University Hospital
🇹ðŸ‡Chiang Mai, Thailand
Karadeniz Teknik University Medical Faculty
🇹🇷Trabzon, Turkey
Asklepios Klinik St. Georg, Haus Lifi - Studien und Projekte GmbH
🇩🇪Hamburg, Germany
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hosp. Virgen Del Rocio
🇪🇸Sevilla, Spain
Nanfang Hospital
🇨🇳Guangzhou, China
Hôpital Beaujon
🇫🇷Clichy, France
Hopital Paul Brousse
🇫🇷Villejuif, France
Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
🇩🇪Berlin, Germany
Universitatsklinikum Essen
🇩🇪Essen, Germany
Hiroshima University Hospital
🇯🇵Hiroshima-shi, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Sverdlovsk Regional Clinical Hospital #1
🇷🇺Ekaterinburg, Russian Federation
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Chang Gung Memorial Hospital Linkou Branch
🇨🇳Tao-Yuan, Taiwan
King Chulalongkorn Memorial Hospital
🇹ðŸ‡Bangkok, Thailand
Prince Of Songkla University
🇹ðŸ‡Songkla, Thailand
Saglık Bilimleri University Şişli Trainig and Research Hospital,Department of Gastroenterology
🇹🇷İstanbul, Turkey
Kharkiv National Medical University, Regional Clinical Infectious Hospital
🇺🇦Kharkiv, Ukraine
Ege University Medical of Faculty, Department of Gastroenterology
🇹🇷Izmir, Turkey
Odessa Regional Clinical Hospital
🇺🇦Odessa, Ukraine
Vinnytsia City Clinical Hospital #1, Department of Infectious Diseases #1
🇺🇦Vinnytsya, Ukraine
North Manchester General Hospital
🇬🇧Crumpsall, United Kingdom
Grahame Hayton Unit
🇬🇧London, United Kingdom
Newcastle upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle upon Tyne, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Hopital Saint-Antoine
🇫🇷Paris, France
Hopital de La Croix Rousse
🇫🇷Lyon, France
Osaka University Hospital
🇯🇵Suita-shi, Japan
National Hospital Organization Nagasaki Medical Center
🇯🇵Nagasaki, Japan
UZ Antwerpen
🇧🇪Edegem, Belgium
SP ZOZ Wroclawskie Centrum Zdrowia
🇵🇱Wroclaw, Poland
ID Clinic
🇵🇱Myslowice, Poland
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Vancouver ID Research and Care Centre Society
🇨🇦Vancouver, British Columbia, Canada
Hospital Sultanah Bahiyah
🇲🇾Alor Setar, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Szpital Specjalistyczny w Chorzowie
🇵🇱Chorzow, Poland
University of Calgary
🇨🇦Calgary, Alberta, Canada
GI Research Institute (G.I.R.I.)
🇨🇦Vancouver, British Columbia, Canada
Beiijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, China
The Chinese University of Hong Kong
ðŸ‡ðŸ‡°Shatin, Hong Kong