A Study to Test Safety and Efficacy of Survodutide (BI456906) in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3)

Phase 2

Completed

• Conditions: Non-alcoholic Steatohepatitis (NASH)
• Interventions: Drug: Survodutide; Drug: Placebo

• Registration Number: NCT04771273
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

This study is open for men and women with a liver disease called nonalcoholic steatohepatitis (NASH) and liver fibrosis. The purpose of the study is to find out whether a medicine called BI 456906 helps patients with NASH and liver fibrosis. The study tests 3 different doses of BI 456906 to find the dose that helps best. Participants are put into 4 groups randomly, which means by chance. There are 3 groups that each receive a different dose of BI 456906 and there is 1 group that receives placebo. BI 456906 and placebo are given as an injection under the skin once per week. The placebo injection looks like the BI 456906 injection but does not contain any medicine.

Participants are in the study for a little over 1 year (60 weeks). During this time, they visit the study site several times and have some video calls in addition. At the visits, the study doctors take different measurements. To see whether the treatment works, the doctors take a very small sample of liver tissue (biopsy) from each participant at the start and at the end of the study. They also examine the liver by ultrasound and MRI. The doctors also regularly check the general health of the participants.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-24
• Study First Submitted QC: 2021-02-24
• Study First Posted: 2021-02-25
• Study Start: 2021-04-27
• Primary Completion: 2023-11-09
• Study Completion: 2023-12-21
• Status Verified: 2024-11
• Results First Submitted: 2024-11-07
• Results First Submitted QC: 2024-11-07
• Last Update Submitted: 2024-11-07
• Results First Posted: 2024-12-03
• Last Update Posted: 2024-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 295

Inclusion Criteria

1. Male or female patients ≥ 18 years (or who are of legal age in countries where that is greater than 18 years) and ≤ 80 years of age at time of consent.
2. Diagnosis of non-alcoholic steatohepatitis (NASH) (Non-alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) ≥ 4, with at least 1 point in inflammation and ballooning each) and fibrosis stage F1-F3 proven by a biopsy conducted during the screening period or by a historical biopsy conducted within the last 6 months prior to randomization and stable body weight defined as less than 5% self-reported change in body weight between the historical biopsy and randomization, if a historical biopsy is used.
3. Liver fat fraction ≥ 8% measured by Magnetic Resonance Imaging (MRI)-Proton Density Fat Fraction (PDFF) and liver stiffness > 6.0 kPa measured by FibroScan® at Visit 1 (if biopsy is scheduled during the screening period MRI-PDFF and FibroScan® assessments have to be performed prior to the biopsy). However, the diagnosis of NASH and fibrosis at liver biopsy (including historical biopsy) is the primary assessment to establish patient eligibility.
4. Patients willing and able to undergo liver biopsies per protocol as judged by the Investigator.
5. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
6. Women of childbearing potential (WOCBP)1 must be willing and able to use two forms of effective contraception where at least one form is highly effective methods of birth control per International Council on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.

Further inclusion criteria apply.

Exclusion Criteria

1. Current or history of significant alcohol consumption (defined as intake of > 210 g/ week in males and > 140 g/ week in females on average over a consecutive period of more than 3 months) or inability to reliably quantify alcohol consumption based on Investigator judgement within the last 5 years.
2. Intake of medications historically associated with liver injury, hepatic steatosis or steatohepatitis within 12 weeks prior to Visit 1. Intake of restricted medications or any medications considered likely to interfere with the safe conduct of the trial.
3. History of other forms of chronic liver disease (e.g., viral hepatitis, autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilson's disease, hemochromatosis, Alpha-1 Antitrypsin (A1At) deficiency, history of liver transplantation). Hepatitis B and C testing will be done at Visit 1. Patients with positive Hepatitis B surface antigen (HBsAg) should be excluded. Patients treated for hepatitis C must have a negative RNA test at screening and also be Hepatitis C Virus (HCV) RNA negative for at least 3 years prior to screening in order to be eligible for the trial.
4. Suspicion, diagnosis, or history of hepatocellular carcinoma (HCC), or any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
5. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, manifest hypo- or hyperthyroidism at Visit 1.
6. History of chronic or acute pancreatitis or elevation of serum lipase/amylase > 2x ULN or fasting serum triglyceride levels of > 500 mg/dL (> 5.65 mmol/L) at screening.
7. Known history of HIV (Human Immunodeficiency Virus) infection and/or tuberculosis and/or an acute COVID-19 infection at Visit 1 (confirmed by SARS CoV-2 RT-PCR test). Further exclusion criteria apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Survodutide 2.4 mg - planned maintenance treatment	Survodutide	-
Survodutide 4.8 mg - planned maintenance treatment	Survodutide	-
Survodutide 6.0 mg - planned maintenance treatment	Survodutide	-
Placebo - planned maintenance treatment	Placebo	-

Primary Outcome Measures

Name	Time	Method
Improvement (Yes/ no) From Baseline in Liver Histological Findings Based on Liver Biopsy After 48 Weeks of Treatment in Patients With NASH (NAS ≥ 4, Fibrosis F1-F3) - Actual Maintenance Treatment	At baseline and at 48 weeks.	Percentage of patients who had an improvement from baseline in liver histological findings based on liver biopsy after 48 weeks of treatment is reported. Percentages were rounded to one decimal place.; Improvement in histological findings was defined as a composite of improvement in NASH and no worsening of fibrosis.; Improvement in non-alcoholic steatohepatitis (NASH) was defined as decrease of at least 2 points in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) with at least 1 point decrease in NAS subscore of either lobular inflammation or ballooning.; The NAS represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease.; The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease.; Patients without post-baseline data were considered non-responders.
Improvement (Yes/ no) From Baseline in Liver Histological Findings Based on Liver Biopsy After 48 Weeks of Treatment in Patients With NASH (NAS ≥ 4, Fibrosis F1-F3) - Planned Maintenance Treatment	At baseline and after 48 weeks of treatment.	Percentage of patients who had an improvement from baseline in liver histological findings based on liver biopsy after 48 weeks of treatment is reported. Percentages were rounded to one decimal place.; Improvement in histological findings was defined as a composite of improvement in non-alcoholic steatohepatitis (NASH) and no worsening of fibrosis.; Improvement in NASH was defined as decrease of at least 2 points in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) with at least 1 point decrease in NAS subscore of either lobular inflammation or ballooning.; The NAS represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease.; The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease.; Patients without post-baseline data were considered non-responders.

Secondary Outcome Measures

Name	Time	Method
Improvement of Liver Fat Content (Yes/ no) Defined as at Least 30% Relative Reduction in Liver Fat Content After 48 Weeks of Treatment Compared to Baseline Assessed by MRI-PDFF - Actual Maintenance Treatment	At baseline and after 48 weeks.	Percentage of participants with improvement in liver fat content is reported. Improvement in liver fat content was defined as percentage reduction from baseline of ≥30% in liver fat content after 48 weeks of treatment compared to baseline. Percentages were rounded to one decimal place.; Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF).; Patients without post-baseline values were imputed as non-responders.
Improvement of Liver Fat Content (Yes/ no) Defined as at Least 30% Relative Reduction in Liver Fat Content After 48 Weeks of Treatment Compared to Baseline Assessed by MRI-PDFF - Planned Maintenance Treatment	At baseline and at 48 weeks.	Percentage of participants with improvement in liver fat content is reported. Improvement in liver fat content was defined as percentage reduction from baseline of ≥30% in liver fat content after 48 weeks of treatment compared to baseline.; Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF).; Patients without post-baseline values were imputed as non-responders.
Absolute Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Actual Maintenance Treatment	MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of absolute change from baseline to Week 48 is reported.	Absolute change of liver fat content (percentage \[%\]) from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF).; Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type \[yes, no\], baseline fibrosis score \[F1, F2, F3\], visit, treatment by visit interaction and baseline by visit interaction as factors.
Absolute Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Planned Maintenance Treatment	MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of absolute change from baseline to Week 48 is reported.	Absolute change of liver fat content from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF).; Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type \[yes, no\], baseline fibrosis score \[F1, F2, F3\], visit, treatment by visit interaction and baseline by visit interaction as factors.
Percent Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Actual Maintenance Treatment	MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of percent change from baseline to Week 48 is reported.	Percent change of liver fat content (percentage \[%\]) from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF).; Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type \[yes, no\], baseline fibrosis score \[F1, F2, F3\], visit, treatment by visit interaction and baseline by visit interaction as factors.
Percent Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Planned Maintenance Treatment	MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of percent change from baseline to Week 48 is reported.	Percent change of liver fat content (percentage \[%\]) from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF).; Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type \[yes, no\], baseline fibrosis score \[F1, F2, F3\], visit, treatment by visit interaction and baseline by visit interaction as factors.
Improvement of Fibrosis (Yes/ no) Defined as at Least One Stage Decrease in Fibrosis Stage After 48 Weeks of Treatment Assessed by Liver Biopsy - Actual Maintenance Treatment	At baseline and after 48 weeks of treatment.	Percentage of participants with improvement of liver fibrosis is reported. Improvement of fibrosis was defined as at least one stage decrease in fibrosis stage after 48 weeks of treatment assessed by liver biopsy.; The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease and the stages of fibrosis based on their location are the following: * 1A Zone 3, perisinusoidal, delicate; * 1B Zone 3, perisinusoidal, dense; * 1C Portal, periportal only; * 2 Zone 3, perisinusoidal + portal, periportal only; * 3 Bridging fibrosis; * 4 Cirrhosis. For analysis purposes no distinction was made between stages 1A, 1B and 1C.
Improvement of Fibrosis (Yes/ no) Defined as at Least One Stage Decrease in Fibrosis Stage After 48 Weeks of Treatment Assessed by Liver Biopsy - Planned Maintenance Treatment	At baseline and after 48 weeks of treatment.	Percentage of participants with improvement of liver fibrosis is reported. Improvement of fibrosis was defined as at least one stage decrease in fibrosis stage after 48 weeks of treatment assessed by liver biopsy.; The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease and the stages of fibrosis based on their location are the following: * 1A Zone 3, perisinusoidal, delicate; * 1B Zone 3, perisinusoidal, dense; * 1C Portal, periportal only; * 2 Zone 3, perisinusoidal + portal, periportal only; * 3 Bridging fibrosis; * 4 Cirrhosis. For analysis purposes no distinction was made between stages 1A, 1B and 1C.
Absolute Change From Baseline in NAS After 48 Weeks of Treatment Assessed by Liver Biopsy - Actual Maintenance Treatment	At baseline and 48 weeks of treatment.	Absolute change from baseline in NAS after 48 weeks of treatment assessed by liver biopsy is reported.; The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease.
Absolute Change From Baseline in NAS After 48 Weeks of Treatment Assessed by Liver Biopsy - Planned Maintenance Treatment	At baseline and 48 weeks of treatment.	Absolute change from baseline in NAS after 48 weeks of treatment assessed by liver biopsy is reported.; The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease.

Trial Locations

Locations (149)

North Alabama Health Research, LLC; 🇺🇸 Huntsville, Alabama, United States

Southern California Research Center; 🇺🇸 Coronado, California, United States

Velocity Clinical Research; 🇺🇸 Panorama City, California, United States

Quest Clinical Research; 🇺🇸 San Francisco, California, United States

Peak Gastroenterology Associates; 🇺🇸 Colorado Springs, Colorado, United States

Integrity Clinical Research, LLC; 🇺🇸 Doral, Florida, United States

Covenant Metabolic Specialists, LLC; 🇺🇸 Sarasota, Florida, United States

Optimus U Corporation; 🇺🇸 Miami, Florida, United States

Sanchez Clinical Research ,Inc; 🇺🇸 Miami, Florida, United States

Ocala GI Research; 🇺🇸 Ocala, Florida, United States

Omega Research Orlando, LLC; 🇺🇸 Orlando, Florida, United States

Gastrointestinal Specialists of Georgia; 🇺🇸 Marietta, Georgia, United States

Digestive Research Alliance of Michiana; 🇺🇸 South Bend, Indiana, United States

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

Delta Research Partners, LLC; 🇺🇸 Bastrop, Louisiana, United States

Centex Studies, Inc.; 🇺🇸 Lake Charles, Louisiana, United States

Tandem Clinical Research; 🇺🇸 Marrero, Louisiana, United States

NECCR PrimaCare Research, LLC; 🇺🇸 Fall River, Massachusetts, United States

National Diabetes and Obesity Research Institute; 🇺🇸 Biloxi, Mississippi, United States

Gastrointestinal Associates; 🇺🇸 Flowood, Mississippi, United States

AIG Digestive Disease Research; 🇺🇸 Florham Park, New Jersey, United States

Northeast GI Research Division; 🇺🇸 Concord, North Carolina, United States

Lucas Research, Inc.; 🇺🇸 Morehead City, North Carolina, United States

Digestive Diseases Research Center; 🇺🇸 Greenwood, South Carolina, United States

Palmetto Clinical Research; 🇺🇸 Summerville, South Carolina, United States

Digestive Health Research, LLC; 🇺🇸 Hermitage, Tennessee, United States

Texas Clinical Research Institute, LLC; 🇺🇸 Arlington, Texas, United States

Texas Liver Institute; 🇺🇸 Austin, Texas, United States

South Texas Research Institute; 🇺🇸 Edinburg, Texas, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

American Research Corporation at the Texas Liver Institute; 🇺🇸 San Antonio, Texas, United States

Pinnacle Clinical Research; 🇺🇸 San Antonio, Texas, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

Gold Coast University Hospital; 🇦🇺 Southport, Queensland, Australia

Monash Medical Centre; 🇦🇺 Clayton, Victoria, Australia

Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

Medical University of Graz State Hospital - University Hospital Graz; 🇦🇹 Graz, Austria

Medical University of Innsbruck; 🇦🇹 Innsbruck, Austria

Ordensklinikum Linz GmbH - Barmherzige Schwestern; 🇦🇹 Linz, Austria

Edegem - UNIV UZ Antwerpen; 🇧🇪 Edegem, Belgium

University Hospital (LHSC); 🇨🇦 London, Ontario, Canada

Toronto Liver Centre; 🇨🇦 Toronto, Ontario, Canada

Ecogene-21; 🇨🇦 Chicoutimi, Quebec, Canada

Beijing Ditan Hospital Capital Medical University; 🇨🇳 Beijing, China

Beijing Tsinghua Changgung Hospital; 🇨🇳 Beijing, China

Peking University People's Hospital; 🇨🇳 Beijing, China

Beijing Friendship Hospital; 🇨🇳 Beijing, China

The First Hospital of Jilin University; 🇨🇳 Changchun, China

The First Afiliated Hospital, Sun Yet-sen University; 🇨🇳 Guangzhou, China

NanFang Hosptial; 🇨🇳 Guangzhou, China

Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine; 🇨🇳 Hangzhou, China

First People's hospital of Yunann Province; 🇨🇳 Kunming, China

The Second Hospital of Nanjing; 🇨🇳 Nanjing, China

Shanghai Public Health Clinical Center; 🇨🇳 Shanghai, China

Tianjin Third Central Hospital; 🇨🇳 Tianjin, China

The First Affiliated Hospital of Wenzhou Med College; 🇨🇳 Wenxzhou, China

Regional Hospital Liberec; 🇨🇿 Liberec, Czechia

General Faculty Hospital, Prague; 🇨🇿 Prague, Czechia

HOP l'Archet; 🇫🇷 Nice, France

HOP La Pitié Salpêtrière; 🇫🇷 Paris, France

HOP Haut-Lévêque; 🇫🇷 Pessac, France

HOP Civil; 🇫🇷 Strasbourg, France

Universitätsklinikum Aachen, AöR; 🇩🇪 Aachen, Germany

Synexus Clinical Research GmbH; 🇩🇪 Leipzig, Germany

Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH; 🇩🇪 Bochum, Germany

Universitätsklinikum Düsseldorf; 🇩🇪 Düsseldorf, Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz; 🇩🇪 Mainz, Germany

Universitätsklinikum Mannheim GmbH; 🇩🇪 Mannheim, Germany

Universitätsklinikum Ulm; 🇩🇪 Ulm, Germany

Attikon University Hospital; 🇬🇷 Haidari-Athens, Greece

General Hospital of Thessaloniki "Hippokrateio"; 🇬🇷 Thessaloniki, Greece

Prince of Wales Hospital; 🇭🇰 Hong Kong, Hong Kong

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong

Synexus Hungary Healthcare Service Ltd.; 🇭🇺 Budapest, Hungary

Fed.St. Istvan&Szent Laszlo Hospital; 🇭🇺 Budapest, Hungary

Synexus Hungary Healthcare Service Ltd; 🇭🇺 Gyula, Hungary

Shaare Zedek Medical Center, Jerusalem 91031; 🇮🇱 Jerusalem, Israel

Western Galilee Hospital; 🇮🇱 Nahariya, Israel

Rabin Medical Center Beilinson; 🇮🇱 Petach Tikva, Israel

Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

The Chaim Sheba Medical Center; 🇮🇱 Tel-Hashomer, Israel

Ospedale Civile di Baggiovara; 🇮🇹 Baggiovara (MO), Italy

A.O. Univ. Policlinico "Paolo Giaccone"; 🇮🇹 Palermo, Italy

Poli Univ A. Gemelli; 🇮🇹 Roma, Italy

Istituto Clinico Humanitas; 🇮🇹 Rozzano (MI), Italy

IRCCS Ospedale "Casa Sollievo della Sofferenza"; 🇮🇹 SAN Giovanni Rotondo (FG), Italy

AO Città della Salute e Scienza; 🇮🇹 Torino, Italy

Ehime University Hospital; 🇯🇵 Ehime, Toon, Japan

Fukuiken Saiseikai Hospital; 🇯🇵 Fukui, Fukui, Japan

Kurume University Hospital; 🇯🇵 Fukuoka, Kurume, Japan

Ogaki Municipal Hospital; 🇯🇵 Gifu, Ogaki, Japan

Japan Community Health Care Organization Hokkaido Hospital; 🇯🇵 Hokkaido, Sapporo, Japan

Kagawa University Hospital; 🇯🇵 Kagawa, Kita-gun, Japan

Kagawa Prefectural Central Hospital; 🇯🇵 Kagawa, Takamatsu, Japan

St. Marianna University Hospital; 🇯🇵 Kanagawa, Kawasaki, Japan

Kitasato University Hospital; 🇯🇵 Kanagawa, Sagamihara, Japan

Yokohama City University Hospital; 🇯🇵 Kanagawa, Yokohama, Japan

National Hospital Organization Yokohama Medical Center; 🇯🇵 Kanagawa, Yokohama, Japan

Kumamoto University Hospital; 🇯🇵 Kumamoto, Kumamoto, Japan

University Hospital Kyoto Prefectural University of Medicine; 🇯🇵 Kyoto, Kyoto, Japan

Shinshu University Hospital; 🇯🇵 Nagano, Matsumoto, Japan

Nagano Municipal Hospital; 🇯🇵 Nagano, Nagano, Japan

Nara Medical University Hospital; 🇯🇵 Nara, Kashihara, Japan

Suita Hospital; 🇯🇵 Osaka, Suita, Japan

Saga University Hospital; 🇯🇵 Saga, Saga, Japan

Hamamatsu University Hospital; 🇯🇵 Shizuoka, Hamamatsu, Japan

Juntendo University Shizuoka Hospital; 🇯🇵 Shizuoka, Izunokuni, Japan

Tokyo Medical and Dental University Hospital; 🇯🇵 Tokyo, Bunkyo-ku, Japan

Pusan National Univ. Hosp; 🇰🇷 Busan, Korea, Republic of

Keimyung University Dongsan Hospital; 🇰🇷 Daegu, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Universiti Sains Malaysia Hospital; 🇲🇾 Kelantan, Malaysia

University of Malaya Medical Centre; 🇲🇾 Kuala Lumpur, Malaysia

Hospital Selayang; 🇲🇾 Selangor, Malaysia

Amsterdam UMC, location VUMC; 🇳🇱 Amsterdam, Netherlands

Leids Universitair Medisch Centrum (LUMC); 🇳🇱 Leiden, Netherlands

Sint Franciscus, Locatie Vlietland; 🇳🇱 Rotterdam, Netherlands

New Zealand Clinical Research (NZCR); 🇳🇿 Auckland, New Zealand

Middlemore Clinical Trials; 🇳🇿 Papatoetoe, New Zealand

INTERCORE Medical Center; 🇵🇱 Bydgoszcz, Poland

Synexus Poland, Branch in Czestochowa; 🇵🇱 Czestochowa, Poland

Private health care facility "Your Health EL" LLC; 🇵🇱 Elblag, Poland

Synexus Polska SCM Sp. z o.o. Gdansku, Gdansk; 🇵🇱 Gdansk, Poland

Synexus Polska Sp. z o.o. Oddzial w Gdyni, Gdynia; 🇵🇱 Gdynia, Poland

University Clinical Center Professor Gibinskiego; 🇵🇱 Katowice, Poland

University Hospital in Krakow; 🇵🇱 Krakow, Poland

Medicome Limited Liability Company; 🇵🇱 Oswiecim, Poland

Centrum Medyczne Synexus; 🇵🇱 Warszawa, Poland

Synexus Poland, Branch in Wroclaw; 🇵🇱 Wroclaw, Poland

ETG Zamosc; 🇵🇱 Zamosc, Poland

ULS de Santa Maria, E.P.E; 🇵🇹 Lisboa, Portugal

Centro Hospitalar Universitário São João,EPE; 🇵🇹 Porto, Portugal

National University Hospital; 🇸🇬 Singapore, Singapore

Singapore General Hospital; 🇸🇬 Singapore, Singapore

Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Puerta de Hierro; 🇪🇸 Majadahonda, Spain

Hospital de Montecelo; 🇪🇸 Pontevedra, Spain

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Spain

Hospital Virgen del Rocío; 🇪🇸 Sevilla, Spain

Hospital General Universitario de Valencia; 🇪🇸 Valencia, Spain

Chia Yi Christian Hospital; 🇨🇳 ChiaYi, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

National Chen Kung University, Dept of Neurology; 🇨🇳 Tainan, Taiwan

Chang Gung Memorial Hospital(Linkou); 🇨🇳 Taoyuan County, Taiwan

Queen Elizabeth Hospital; 🇬🇧 Birmingham, United Kingdom

Synexus - Hexham; 🇬🇧 Hexham, United Kingdom

Aintree University Hospital; 🇬🇧 Liverpool, United Kingdom

King's College Hospital; 🇬🇧 London, United Kingdom

Queen's Medical Centre; 🇬🇧 Nottingham, United Kingdom