A Long-Term Study of Elafibranor in Adult Participants With Primary Biliary Cholangitis

Phase 3

Recruiting

• Conditions: Primary Biliary Cholangitis (PBC)
• Interventions: Other: Matched 80 mg placebo; Drug: Elafibranor

• Registration Number: NCT06016842
• Lead Sponsor: Ipsen

Brief Summary

The participants of this study will have confirmed Primary Biliary Cholangitis (PBC) and cirrhosis (scarring of the liver).

PBC is a slowly progressive disease, characterised by damage to the bile ducts in the liver, leading to a build-up of bile acids which causes further damage.

The liver damage in PBC may lead to cirrhosis. PBC may also be associated with multiple symptoms. Many patients with PBC may require liver transplant or may die if the disease progresses and a liver transplant is not done.

This study will compare a daily dose of elafibranor (the study drug) to a daily dose of placebo (a dummy treatment) and will last up to 3.5 years for each participant.

The main aim of this study is to determine if elafibranor is better than placebo in preventing clinical outcome events showing disease worsening (including progression of disease leading to liver transplant or death).

This study will also study the safety of long-term treatment with elafibranor, as well as the impact on symptoms such as itching and tiredness.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-22
• Study First Submitted QC: 2023-08-29
• Study First Posted: 2023-08-30
• Study Start: 2023-08-31
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-20
• Last Update Posted: 2024-12-27
• Primary Completion: 2029-05-31
• Study Completion: 2029-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 276

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Matched 80 mg placebo	Participants will take 1 placebo tablet per day orally (matching the 80 mg elafibranor sized tablet) before breakfast with a glass of water at approximately the same time each morning.
Elafibranor 80 mg	Elafibranor	Participants will take 1 tablet of elafibranor 80 mg per day orally before breakfast with a glass of water at approximately the same time each morning.

Primary Outcome Measures

Name	Time	Method
Event-free survival	From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years)	Event-free survival is defined as the time from randomisation to either adjudicated disease progression or death, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Percentage of participants experiencing Treatment Emergent Adverse Events (TEAEs), treatment-related TEAEs, Serious Adverse Events (SAEs), and Adverse Events of Special Interests (AESIs)	From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years)	An Adverse event (AE) is any untoward medical occurrence, temporally associated with the use of study intervention, whether or not related to the study intervention. AESIs are AEs that may not be serious but are of special importance to a particular drug or class of drugs.
Percentage of participants developing clinically significant changes in physical examination findings	From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years)	Complete physical examination at screening and targeted examination at all other clinical visit timepoints.
Percentage of participants developing clinically significant changes in vital signs	From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years)	Percentage of participants with clinically significant changes in Vital Signs will be reported. The clinical significance will be graded by the investigator.
Percentage of participants developing clinically significant changes in Electrocardiogram (ECG) readings.	From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years)	Percentage of participants with clinically significant changes in ECG readings will be reported. The clinical significance will be graded by the investigator.
Percentage of participants with clinically significant changes in laboratory parameters (blood chemistry, hematology, coagulation and urinalysis)	From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years)	Percentage of participants with clinically significant change in laboratory parameters (blood chemistry, hematology and coagulation) will be reported. The clinical significance will be graded by the investigator.
Change from baseline in Alkaline phosphatase (ALP)	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in Total Bilirubin (TB)	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP≤ 1.67x ULN and TB≤ ULN	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with complete biochemical response	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)	Defined as normal levels of TB, ALP, transaminases, albumin, and International normalised ratio (INR)
Percentage of participants with normalisation of TB and ALP	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)	Defined as TB\< Upper Limit Normal (ULN) and ALP\< ULN
Percentage of participants with stabilisation in TB (i.e. no increase)	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)	Defined as TB\< 1x ULN or increase from baseline \<0.1x ULN
Percentage of participants with a response based on albumin normalisation	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in liver stiffness measurement (LSM)	At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)	Assessed by vibration-controlled transient elastography (VCTE) using Fibroscan® on the day of the visit.
Change from baseline in PBC risk scores based in Global PBC Study Group (GLOBE) score	At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)	The GLOBE score is a validated risk assessment tool providing an estimate of transplant-free survival for patients with PBC. It was developed by the Global PBC Study Group using Cox regression model on over 4,000 patients with PBC. Lower GLOBE score predicts lower risk. It is calculated from the following equation: GLOBE score = (0.044378 \* age + 0.93982 \* LN(total bilirubin/ULN) +(0.335648 \* LN(alkaline phosphatase/ULN)) - 2.266708 \* albumin /LLN -0.002581 \* platelet count per 109/L) + 1.216865; GLOBE scoring system, which calculation is based on serum values of bilirubin, ALP, albumin and platelet count after 1 year of treatment and age at baseline. A high number is indicative of a worse score.
Change from baseline in PBC risk scores based on United Kingdom (UK)-PBC score.	At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)	PBC risk score developed by United Kingdom (UK)-PBC Consortium is a scoring system and the calculation is based on laboratory test measurements and upper limits of normal (ULN) for the total bilirubin (BIL12); alanine transaminase or aspartate transaminase (TA12), and alkaline phosphatase (ALP12) after at least 12 months of UDCA, and the laboratory test measurements and lower limits of normal (LLN) for the serum albumin and platelet count in the same timeframe. A high number is indicative of a worse score.
Percentage of participants with LSM ≥15 kPa	At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)	Assessed by VCTE using Fibroscan®
Change in serum levels of Aspartate aminotransferase (AST) compared to the baseline	At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change in serum levels of ALT compared to the baseline	At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change in serum levels of Gamma-glutamyl transferase (GGT) compared to the baseline	At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in hepatic function: Conjugated bilirubin	At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change in serum levels of Albumin compared to the baseline	At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in hepatic function: international normalised ratio (INR)	At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in hepatic function: fractionated ALP	At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with no worsening of LSM	At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)	Assessed by VCTE using Fibroscan® defined as no increase \>2kPa from baseline
Percentage of participants with ALP reduction of 40%	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP <1.5x ULN, ALP decrease ≥15% and TB ≤ULN	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP <1.5x ULN, ALP decrease ≥40% and TB ≤ULN	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP <1.67x ULN, ALP decrease ≥15% and TB ≤ULN	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP <3x ULN, AST <2x ULN and TB ≤1 mg/dL (Paris I)	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP ≤1.5x ULN, AST ≤1.5x ULN and TB ≤1 mg/dL (Paris II criteria)	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with normalisation of abnormal TB	Assessed at Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with normalisation of abnormal TB and albumin (Rotterdam criteria)	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with reduction in TB to ≤0.6x ULN in participants with TB >0.6x ULN at baseline	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in lipid parameters: total cholesterol (TC)	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in lipid parameters: high density lipoprotein cholesterol (HDL-C)	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in lipid parameters: calculated very low density lipoprotein cholesterol (VLDL-C)	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in lipid parameters: low density lipoprotein cholesterol (LDL-C)	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in lipid parameters: triglycerides (TG)	At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with a response in PBC Worst Itch NRS score	Through 6 months up to end of treatment (maximum duration of 3.5 years)	Defined as ≥2-point reduction from baseline NRS in participants with a baseline NRS ≥4
Percentage of participants with a response in PBC Worst Itch NRS	Assessed through 6 months up to end of treatment (maximum duration of 3.5 years)	Defined as ≥3-point reduction from baseline NRS in participants with a baseline NRS ≥4
Change from baseline in 5D-Itch scale	Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)	Questionnaire that assesses symptoms in terms of 5 domains: degree, duration, direction, disability and distribution. Participants rate their symptoms over the preceding 2-week period on a 1 to 5 scale, with 5 being the most affected.
Change from baseline in Patient Global Impression of Severity (PGI-S)	Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)	A 1-item, 5-point scale designed to assess the participant's impression of disease severity
Patient Global Impression of Change (PGI-C)	Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)	A 1-item, 5-point scale designed to assess the participant's impression of change in disease severity since the baseline visit
Change from baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form 7a	Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)	Consists of 7 items that measure both the experience of fatigue and the interference of fatigue on daily activities over the past week. Response options are on a 5-point Likert scale, ranging from 1 to 5. Scores can range from 7 to 35, with higher scores indicating greater fatigue.
Change from baseline in the Epworth Sleepiness Scale (ESS)	Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)	Self-administered questionnaire that consists of 8 questions asking to rate how likely it is to fall asleep in different situations commonly encountered in daily life (each question can be scored from 0 to 3 points; '0' indicates no sleepiness, '3' indicates significant sleepiness). It provides a total score which has been shown to relate to the participant's level of daytime sleepiness (total score range 0-24 points).
Change from baseline in PBC-40 score	Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)	40-item questionnaire that assesses symptoms across 6 domains: fatigue, emotional and social, cognitive function, general symptoms and itch. Participants respond on a verbal response scale, depending on the section options range from 'never' / 'not at all' / 'strongly disagree' to 'always' / 'very much' / 'strongly agree'. Six items (3/3 in the itch domain, 2/10 in the social domain, and 1/7 in the general symptoms domain) also include a 'does not apply' option. A score for each domain is provided (but a total score is not calculated), with each verbal response scale correlating to a score of 1 to 5 per item (0 to 5 on items with a 'does not apply' option) with 5 being the most affected (greatest burden). The PBC-40 has a 4-week recall period.
Change from baseline in PBC Worst Itch Numeric Rating Scale (NRS) score	Assessed through 6 months up to end of treatment (maximum duration of 3.5 years)	Self-administered patient-reported outcome questionnaire that measures itch intensity. It asks participants to rate the intensity of their Worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (Worst Itch imaginable): - once daily (24-hour recall period) using the eDiary during the screening and initial 2 years of the study, - at the clinic visits (7-day recall period), from Year 3 onwards
Change from baseline in EuroQol 5-dimensional 5-level questionnaire (EQ-5D-5L)	Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)	Self-administered standardised questionnaire that assesses the 5-dimensions of mobility, self-care, usual activities, pain/discomfort, anxiety/depression descriptively (each dimension has 5 levels) and the overall health state via an EQ Visual Analogue Scale (VAS).
Change from baseline in Work Productivity and Activity Impairment General Health (WPAI-GH)	Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)	Questionnaire that measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. It consists of 6 questions: 1=currently employed; 2=hours missed because of health problems; 3=hours missed because of other reasons; 4=hours actually worked; 5=degree health affected productivity while working (using a 0 to 10 Visual Analogue Scale (VAS)); 6=degree health affected productivity in regular unpaid activities (VAS).
Time to the first occurrence of each of individual adjudicated clinical outcome events	From baseline until 4 weeks after the end of treatment	Among: • All-cause mortality • Liver-related mortality • Liver transplant • MELD-3.0 score ≥15 in participants with baseline MELD score ≤12 • Liver decompensation • Occurrence of hepatocellular carcinoma
Area under the plasma concentration-time curve from time 0 to 24 hours: AUC0-24	At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
Maximum (peak) plasma drug concentration: Cmax	At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
Time to reach maximum (peak) plasma concentration following drug administration): Tmax	At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
Apparent clearance of drug from plasma (CL)	At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
Apparent volume of distribution (VZ)	At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
Change from baseline in model for end-stage liver disease (MELD) 3.0 score	From screening until end of treatment (maximum duration of 3.5 years)	The MELD 3.0 score is calculated from parameters (sex, creatinine, bilirubin, INR, sodium and albumin) where a high score indicates a greater risk of needing a liver transplant.
Change from baseline in Child Pugh grade	From screening until end of treatment (maximum duration of 3.5 years)	Child Pugh grade is calculated using bilirubin, albumin, INR, ascites and encephalopathy.; A high grade is indicative of worse liver disease.

Trial Locations

Locations (130)

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Clinica Universidad Navarra-Sede Madrid; 🇪🇸 Madrid, Spain

Hospital General Universitario Gregorio Maranon (HGUGM); 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitario Puerta de Hierro de Majadahonda; 🇪🇸 Majadahonda, Spain

Hospital Universitario Virgen de la Victoria; 🇪🇸 Málaga, Spain

Hospital De Montecelo; 🇪🇸 Pontevedra, Spain

Institut d Investigacio i Innovacio Parc Tauli, Hospital Universitari Parc Tauli; 🇪🇸 Sabadell, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

Hospital Universitario y Politecnico La Fe; 🇪🇸 Valencia, Spain

Hospital Universitario Rio Hortega; 🇪🇸 Valladolid, Spain

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

Enroll SpA; 🇨🇱 Santiago, Chile

Hospital Clinic i Provincial de Barcelona; 🇪🇸 Barcelona, Spain

University of Alberta - Faculty of Medicine & Dentistry - The Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR); 🇨🇦 Edmonton, Canada

University Health Network (UHN) - Toronto General Hospital (TGH) - Toronto General Research Institute (TGRI); 🇨🇦 Toronto, Canada

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea, Eunpyeong St. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

Arizona Liver Health; 🇺🇸 Tucson, Arizona, United States

Arkansas Diagnostic Center, PA; 🇺🇸 Little Rock, Arkansas, United States

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

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

GastroIntestinal BioSciences; 🇺🇸 Los Angeles, California, United States

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

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

South Denver Gastroenterology, P.C.; 🇺🇸 Englewood, Colorado, United States

Rocky Mountain Gastroenterology; 🇺🇸 Littleton, Colorado, United States

University Of Miami School Of Medicine, Center For Liver Diseases; 🇺🇸 Miami, Florida, United States

International Center for Research; 🇺🇸 Tampa, Florida, United States

Louisiana Research Center, LLC; 🇺🇸 Shreveport, Louisiana, United States

University of Michigan Health System; 🇺🇸 Ann Arbor, Michigan, United States

Huron Gastroenterology Associates - Center for Digestive Care; 🇺🇸 Ypsilanti, Michigan, United States

Southwest Gastroenterology Associates, PC (SWGA); 🇺🇸 Albuquerque, New Mexico, United States

NYU Langone Gastroenterology and Hepatology Associates; 🇺🇸 New York, New York, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Gastroenterology Center of the Midsouth; 🇺🇸 Cordova, Tennessee, United States

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

American Research Corporation; 🇺🇸 Austin, Texas, United States

Rush University Medical Center - University Cardiovascular Surgeons; 🇺🇸 Dallas, Texas, United States

Liver Center of Texas; 🇺🇸 Dallas, Texas, United States

Methodist Transplant Physicians; 🇺🇸 Dallas, Texas, United States

University of Texas Southwestern Medical Center at Dallas; 🇺🇸 Dallas, Texas, United States

Baylor Scott & White All Saints Medical Center - Forth Worth; 🇺🇸 Fort Worth, Texas, United States

Liver Associates of Texas; 🇺🇸 Houston, Texas, United States

Houston Methodist Cancer Center; 🇺🇸 Houston, Texas, United States

Gastro health & Nutrition; 🇺🇸 Katy, Texas, United States

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

Impact Research Tx; 🇺🇸 Waco, Texas, United States

University of Virginia Medical Center; 🇺🇸 Charlottesville, Virginia, United States

Bon Secours St. Mary's Hospital of Richmond, Inc; 🇺🇸 Richmond, Virginia, United States

Virginia Commonwealth University Medical Center - West Hospital; 🇺🇸 Richmond, Virginia, United States

Medstar Georgetown Transplant Institute University Hospital (MGUH); 🇺🇸 Columbia, Washington, United States

Velocity Clinical Research at Liver Institute Northwest; 🇺🇸 Seattle, Washington, United States

Fundacion Respirar (Centro Medico Dra. De Salvo) - Instituto Argentino de Investigaciones Clinicas (IAIC) S.R.L; 🇦🇷 Buenos Aires, Argentina

Hospital Britanico de Buenos Aires; 🇦🇷 Buenos Aires, Argentina

Hospital Italiano de Buenos Aires; 🇦🇷 Buenos Aires, Argentina

Centro Medico Colon; 🇦🇷 Córdoba, Argentina

Hospital Espanol de Mendoza; 🇦🇷 Mendoza, Argentina

Hospital Universitario Austral; 🇦🇷 Pilar, Argentina

Sunshine Coast University Hospital; 🇦🇺 Birtinya, Australia

Footscray Hospital, Western Health; 🇦🇺 Footscray, Australia

Nepean Clinical School; 🇦🇺 Kingswood, Australia

Monash University - Monash Health -Monash Medical Centre; 🇦🇺 Melbourne, Australia

St George Hospital; 🇦🇺 Sydney, Australia

Westmead Hospital; 🇦🇺 Westmead, Australia

Universitair Ziekenhuis Antwerpen; 🇧🇪 Edegem, Belgium

Ziekenhuis Oost-Limburg; 🇧🇪 Genk, Belgium

Gent University Hospital; 🇧🇪 Gent, Belgium

Algemeen Ziekenhuis Delta; 🇧🇪 Roeselare, Belgium

Hospital de Clinicas de Porto Alegre (HCPA); 🇧🇷 Porto Alegre, Brazil

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; 🇧🇷 São Paulo, Brazil

Hospital de Base - Centro Integrado de Pesquisa ( CIP ); 🇧🇷 São Paulo, Brazil

Universidade Estadual Paulista Julio De Mesquita Filho (UNESP) Hospital das Clinicas Faculdade de Medicina de Botucatu (HCFMB); 🇧🇷 São Paulo, Brazil

Universidad De Los Andes; 🇨🇱 Las Condes, Chile

University of Chile Clinical Hospital (Hospital Clinico de la Universidad de Chile); 🇨🇱 Santiago, Chile

Centro Medico Cedid - Centro de Diagnostico Digestivo; 🇨🇱 Viña Del Mar, Chile

Hepato-Gastroenterologie HK, s.r.o.; 🇨🇿 Hradec Králové, Czechia

Krajska Nemocnice Liberec; 🇨🇿 Liberec, Czechia

Artroscan; 🇨🇿 Ostrava, Czechia

Research Site s.r.o.; 🇨🇿 Plzen, Czechia

Institute for Clinical and Experimental Medicine - IKEM; 🇨🇿 Prague, Czechia

Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez; 🇫🇷 Lille, France

Hospices Civils de Lyon (HCL) - Hopital de la Croix-Rousse; 🇫🇷 Lyon, France

Hopital Saint Joseph - Marseille; 🇫🇷 Marseille, France

CHU de Nice, Hopital de l'Archet; 🇫🇷 Nice, France

Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Universitaire Pitie Salpetriere (Hopital Pitie-Salpetriere); 🇫🇷 Paris, France

CHU Poitiers; 🇫🇷 Poitiers, France

Clinique Pasteur; 🇫🇷 Toulouse, France

Hopital Paul-Brousse - APHP; 🇫🇷 Villejuif, France

Azienda Ospedaliero Universitaria Modena; 🇮🇹 Modena, Italy

Ospedale San Gerardo; 🇮🇹 Monza, Italy

Azienda Ospedaliero Universitaria Federico II di Napoli; 🇮🇹 Naples, Italy

Azienda Ospedaliera di Padova - U.O.C. di Gastroenterologia; 🇮🇹 Padova, Italy

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone; 🇮🇹 Palermo, Italy

Fondazione I.R.C.C.S. Policlinico San Matteo; 🇮🇹 Pavia, Italy

Azienda Ospedaliero Universitaria Pisana; 🇮🇹 Pisa, Italy

Ospedale Casa Sollievo della Sofferenza; 🇮🇹 San Giovanni Rotondo, Italy

Pusan National University Hospital (PNUH); 🇰🇷 Busan, Korea, Republic of

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

The Catholic University of Korea Daejeon St.Mary's Hospital; 🇰🇷 Daejeon, Korea, Republic of

Korea University Ansan Hospital; 🇰🇷 Gyeonggi-do, Korea, Republic of

Kyungpook National University Hospital (KNUH); 🇰🇷 Junggu, Korea, Republic of

CHA Bundang Medical Center, CHA University; 🇰🇷 Seongnam-si, Korea, Republic of

Chung-Ang University Hospital; 🇰🇷 Seoul, Korea, Republic of

Hallym University Kangnam Sacred Heart Hospital; 🇰🇷 Seoul, Korea, Republic of

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

Seoul National University Bundang Hospital (SNUBH); 🇰🇷 Seoul, Korea, Republic of

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

Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea, Uijeongbu St. Mary's Hospital; 🇰🇷 Uijeongbu, Korea, Republic of

Centro de Investigacion y Gastroenterologia SC; 🇲🇽 Ciudad de mexico, Mexico

Centro de Investigacion Medico Biologica y Terapia Avanzada; 🇲🇽 Jalisco, Mexico

Medical Care & Research; 🇲🇽 Yucatán, Mexico

Canterbury District Health Board; 🇳🇿 Christchurch, New Zealand

Waikato Hospital; 🇳🇿 Hamilton, New Zealand

NZOZ Twoje Zdrowie EL Sp. z o.o.; 🇵🇱 Elbląg, Poland

Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego; 🇵🇱 Katowice, Poland

Krakowskie Centrum Medyczne Sp.z.o.o - FutureMeds; 🇵🇱 Kraków, Poland

Szpital Uniwersytecki w Krakowie; 🇵🇱 Kraków, Poland

Krakowskie Centrum Medyczne Sp.z.o.o. - FutureMeds; 🇵🇱 Małogoskie, Poland

Niepubliczny Zaklad Opieki Zdrowotnej (NZOZ) - Poliklinika Doktora Bessera; 🇵🇱 Sosnowiec, Poland

FutureMeds Warszawa Centrum; 🇵🇱 Warszawa, Poland

FutureMeds sp. z o. o; 🇵🇱 Wrocław, Poland

Centrul Pentru Studiul Metabolismului; 🇷🇴 Bucharest, Romania

Sana S.R.L; 🇷🇴 Bucharest, Romania

Spital Clinic Dr I Cantacuzino; 🇷🇴 Bucharest, Romania

Cluj County Clinical Emergency Hospital; 🇷🇴 Cluj-Napoca, Romania

Gastromedica Srl; 🇷🇴 Iaşi, Romania