A Trial of Setanaxib in Patients With Primary Biliary Cholangitis (PBC) and Liver Stiffness

Phase 2

Completed

Conditions: Primary Biliary Cholangitis
Liver Stiffness

Interventions: Drug: Setanaxib
Drug: Placebo

Registration Number: NCT05014672

Lead Sponsor: Calliditas Therapeutics Suisse SA

Brief Summary: The primary objective of this study is to evaluate the effect of setanaxib on alkaline phosphatase (ALP) at Week 24 in participants with PBC and with elevated liver stiffness and intolerance or inadequate response to ursodeoxycholic acid (UDCA).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 76

Inclusion Criteria

Male or female participant aged ≥18 years, inclusive at the time of informed consent.
Willing and able to give written informed consent and to comply with the requirements of the study.
Definite or probable PBC diagnosis as demonstrated by the presence of ≥2 of the following 3 diagnostic factors:
- Documented history of elevated ALP levels ≥1.67×ULN of the local reference range.
- Documented history of positive antimitochondrial antibodies (AMA) titer or positive PBC-specific antibodies (anti-GP210 or anti-SP100 or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex]).
- Historical liver biopsy consistent with PBC.
Serum ALP ≥1.67×ULN at Screening.
Liver stiffness measured by transient elastography (FibroScan®) of ≥8.8 kilopascals (kPa) and an interquartile range over median ratio (IQR/med) of ≤30% at Screening, are taken with the results expressed in kilopascals).
Ursodeoxycholic acid (UDCA) prescriptional dose use for the past 6 months (at a stable dose for >3 months prior to Screening) OR intolerant to UDCA (last dose of UDCA >3 months prior to Screening). Intolerance to UDCA is defined as participants unable to tolerate the full-labelled dose of UDCA in PBC (13-15 mg/kg) due to frequently reported gastrointestinal symptoms such as diarrhea and abdominal pain.
For participants receiving obeticholic acid (OCA), fenofibrate, or bezafibrate treatment for at least 6 months and stable dose for >3 months prior to Screening.
For participants intolerant to OCA, OCA must have been discontinued >3 months prior to Screening.
For participants previously treated with bezafibrate or fenofibrate, and these agents were discontinued prior to screening, they must have been discontinued >3 months prior to Screening.
Female participants of childbearing potential must use a highly effective method of contraception to prevent pregnancy for ≥4 weeks before Randomization and must agree to continue strict contraception up to 90 days after the last dose of investigational medicinal product (IMP).
- For the purposes of this trial, women of childbearing potential are defined as "Fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy."
- Postmenopausal state is defined as no menses for 12 months without an alternative medical cause. In female participants who are not using hormonal contraception or hormonal replacement therapy but with suspected menopause and less than 12 months of amenorrhea, a high follicle stimulating hormone (FSH) level in the postmenopausal range will be required at Screening to confirm a postmenopausal state. Confirmation with more than one FSH measurement is required.
- Highly effective contraception is defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. These methods are:
  - Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal)
  - Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)
  - Intrauterine device
  - Intrauterine hormone-releasing system
  - Bilateral tubal occlusion
  - Vasectomized partner
  - Sexual abstinence (refraining from heterosexual intercourse during the entire period of risk associate with the study treatments). The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
Female participants of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline/Randomization before dosing.
Male participants with female partners of childbearing potential must be willing to use a condom and require their partner to use a highly effective contraceptive method. This requirement begins at the time of informed consent and ends 90 days after receiving the last dose of IMP.
Male participants must be willing not to donate sperm, and female study participants must be willing not to donate eggs, from Baseline until 90 days after the last dose of IMP.

Exclusion Criteria

A positive pregnancy test or breastfeeding for female participants.
Any historical or current hepatic decompensation event defined as variceal/portal hypertension bleed and/or hepatic encephalopathy, spontaneous bacterial peritonitis, ascites requiring treatment, or liver transplantation list inclusion.
History of liver transplantation, current placement on a liver transplant list or current model for end stage liver disease (MELD) score of ≥12 unless the participant is on anticoagulant therapy, or a Child-Pugh Score of ≥6.
Cirrhosis with complications, including history or presence of hepatocellular carcinoma.
Total bilirubin >2×ULN. In case of total bilirubin elevation >ULN the Screening serum albumin must be within the reference range.
Plasma alanine aminotransferase (ALT) >3×ULN and/or aspartate aminotransferase (AST) >3×ULN.
International normalized ratio (INR) >1.2 unless participant is on anticoagulant therapy. One repeat blood sampling (with analysis by the central laboratory) can be performed at the discretion of the Investigator at Screening Visit 2 for participants who meet this exclusion criterion at Screening Visit 1. If this exclusion criterion is not met at Screening Visit 2, the participant may be eligible for the study.
Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2, as calculated by the central laboratory using the chronic kidney disease-epidemiology collaboration (CKD- EPI) equation.
Thyroid-stimulating hormone >ULN at Screening. One repeat blood sampling (with analysis by the central laboratory) can be performed at the discretion of the Investigator at Screening Visit 2 for participants who meet this exclusion criterion at Screening Visit 1. If this exclusion criterion is not met at Screening Visit 2, the participant may be eligible for the study.
Competing etiology for liver disease (eg, hepatitis C [unless effectively cured of hepatitis C, with a sustained virologic response for at least 6 months prior to Screening], active hepatitis B [HBsAg positive], nonalcoholic steatohepatitis [NASH], alcoholic liver disease, autoimmune hepatitis, autoimmune hepatitis-PBC overlap syndrome, primary sclerosing cholangitis, Gilbert's Syndrome).
Medical conditions that could cause nonhepatic increases in ALP (eg, Paget's disease).
Known history of human immunodeficiency virus (HIV) infection.
Surgery (eg, stomach bypass) or medical condition that might significantly affect absorption of medicines (as judged by the Investigator).
Positive urine drug screen (if not due to prescriptional use of a concomitant medication, as confirmed by the Investigator) at Screening. Participants on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to Screening Visit 1 may be included in the study. Medicinal cannabis and cannabidiol products are not exclusionary and may be allowed if the prescription and diagnosis are reviewed and approved by the Investigator.
Participants receiving prohibited medications within 3 months of Screening Visit 1.
Treatment with any investigational agent within 12 weeks of Screening Visit 1 or 5 half-lives of the IMP (if known) (whichever is longer) or current enrollment in an interventional clinical trial.
Evidence of any of the following cardiac conduction abnormalities: A QTc Fridericia interval >450 milliseconds for males or >470 milliseconds for females, as calculated by the central reader. Participants with a second- or third-degree atrioventricular block are to be excluded.
History of a malignancy within 5 years of Screening with the following exceptions:
- Adequately treated carcinoma in situ of the cervix.
- Adequately treated basal or squamous cell cancer or other localized nonmelanoma skin cancer.
The occurrence of any acute infection requiring systemic antibiotic therapy within the 2 weeks prior to Screening Visit 1.
A history of bone marrow disorder including aplastic anemia, or any current marked anemia defined as hemoglobin <10.0 g/dL.
Prior treatment with setanaxib or participation in a previous setanaxib clinical trial.
Unstable cardiovascular disease.
Presence of any laboratory abnormality or condition that, in the opinion of the Investigator, could interfere with or compromise a participant's treatment, assessment, or compliance with the protocol and/or study procedures.
Any other condition which, in the opinion of the Investigator, constitutes a risk or contraindication for the participation of the participant in the study, or that could interfere with the study objectives, conduct, or evaluation.
Hypersensitivity or intolerance to setanaxib or to any of its excipients or placebo compounds.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Setanaxib 1200 mg/day	Setanaxib	Participants will be administered setanaxib at a dose of 1200 mg/day for the 24-week double-blind treatment period.
Placebo	Placebo	Participants will be administered a placebo for the 24-week double-blind treatment period.
Setanaxib 1600 mg/day	Setanaxib	Participants will be administered setanaxib at a dose of 1600 mg/day for the 24-week double-blind treatment period.

Primary Outcome Measures

Name	Time	Method
Change in ALP at Week 24 Compared to Baseline	Baseline (Day 1) and Week 24	Change in ALP at Week 24 Compared to Baseline, ratio of week 24 value to baseline value.

Secondary Outcome Measures

Name	Time	Method
Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the PROMIS Short Form-Fatigue 7b Daily	Baseline (Day 1) and Week 24	The Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7b measures the severity of fatigue since waking. There are 7 questions, each scored between 1 and 5, with a total score between 7 to 35. A higher score indicates worse fatigue. This raw score is converted to a T score (a standardized score with a mean of 50 and a SD of 10).
Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the Patient's Global Impression of Severity (PGIS) Fatigue	Baseline (Day 1) and Week 24	The Patient's Global Impression of Severity (PGIS)-Fatigue is a global index where subjects are asked to rate the severity of fatigue on a 5-point scale within the past 7 days, with choices of 1=None, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe. Higher scores indicate a worse assessment for fatigue.
Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the Patient's Global Impression of Change (PGIC) Fatigue	Week 24	The Patient's Global Impression of Change (PGIC)-Fatigue is a 7-point scale reflecting a subject's rating of overall improvement where subjects are asked to rate their overall improvement with fatigue with 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Worse, 6=Much worse, 7=Very much worse. Higher scores indicate a worse outcome for change in fatigue.
Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the PBC-40 Questionnaire (PBC 40) Fatigue Domain	Baseline (Day 1) and Week 24	PBC-40 fatigue domain includes 11 item questions, items scores range from 1 to 5. The individual item scores are summed to obtain a total domain score (Range for fatigue domain: 11 to 55), high scores represent high impact and low scores indicate low impact of PBC on the quality of life.
Change in Liver Stiffness at Week 24 Compared to Screening	Screening (Day -28) and Week 24	Change in liver stiffness at Week 24 compared to Screening, as assessed by transient elastography (FibroScan®)
Change in Pruritus at Week 24 Compared to Baseline, as Assessed by the Worst Itch Numerical Rating Scale (WI-NRS)	Baseline (Day 1) and Week 24	WI-NRS is a daily patient-reported measure of itch intensity using an 11-point scale where 0=no itch and 10=worst itching imaginable. The WI-NRS score is calculated by averaging the daily WI-NRS scores before the visit date (inclusive). Higher scores indicate worse functioning for pruritus on the WI-NRS.
Change in Pruritus at Week 24 Compared to Baseline, as Assessed by the PBC-40 Itch Domain	Baseline (Day 1) and Week 24	Pruritus was assessed by answering 3 questions on the PBC-40 Itch domain from 1 to 5, which was also summed to obtain a total domain score (range 3 to 15). A high score represents a high impact, and a low score indicates low impact of pruritus on the quality of life.
Change in Pruritus at Week 24 Compared to Baseline, as Assessed by the PGIS Pruritus	Baseline (Day 1) and Week 24	PGIS-Pruritus is a global index where subjects are asked to rate the severity of pruritus on a 5-point scale within the past 7 days, with choices of 1=None, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe. Higher scores indicate a worse assessment for pruritus.
Change in Pruritus at Week 24 Compared to Baseline, as Assessed by the PGIC Pruritus	Week 24	The PGIC-Pruritus is a 7-point scale reflecting a subject's rating of overall improvement where subjects are asked to rate their overall improvement with fatigue with 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Worse, 6=Much worse, 7=Very much worse. Higher scores indicate a worse outcome for change in pruritus.
Changes in Markers of Cholestasis at Week 24	Baseline (Day 1) and Week 24	Changes in markers of cholestasis as assessed by proportion of patients at Week 24 with: * ALP reduction to \<1.67×ULN and total bilirubin ≤1×ULN and a ≥15% or ≥30% or ≥40% or ≥70% ALP reduction from Baseline, respectively * ALP reduction to \<1.5×ULN and total bilirubin ≤1×ULN and a ≥40% ALP reduction from Baseline * ALP \<1×ULN and total bilirubin ≤1×ULN * Total bilirubin \<0.6×ULN
Change in ALP at Week 24 Compared to Baseline, Where Setanaxib Doses Are Combined	Baseline (Day 1) and Week 24	Change in ALP at Week 24 Compared to Baseline, ratio of week 24 value to baseline value. Setanaxib doses are combined and the change from baseline is estimated using a mixed model-repeated measures approach with fixed factors for treatment, visit, log(baseline), treatment\visit, and log(baseline)\visit, subject is included as a random effect. The variance-covariance matrix is therefore not the same as in the three arm analysis, which causes treatment effects estimated in the placebo to group differ from those estimated in the analysis with three treatment arms.
Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the PROMIS Short Form-Fatigue 7b Daily, Where Setanaxib Doses Are Combined	Baseline (Day 1) and Week 24	The Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7b measures the severity of fatigue since waking. There are 7 questions, each scored between 1 and 5, with a total score between 7 to 35. A higher score indicates worse fatigue. This raw score is converted to a T score (a standardized score with a mean of 50 and a SD of 10). Setanaxib doses are combined and the change from baseline is estimated using a mixed model-repeated measures approach with fixed factors for treatment, visit, log(baseline), treatment\visit, and log(baseline)\visit, subject is included as a random effect. The variance-covariance matrix is therefore not the same as in the three arm analysis, which causes treatment effects estimated in the placebo to group differ from those estimated in the analysis with three treatment arms.
Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the PBC-40 Questionnaire (PBC 40) Fatigue Domain, Where Setanaxib Doses Are Combined	Baseline (Day 1) and Week 24	PBC-40 fatigue domain includes 11 item questions, items scores range from 1 to 5. The individual item scores are summed to obtain a total domain score (Range for fatigue domain: 11 to 55), high scores represent high impact and low scores indicate low impact of PBC on the quality of life. Setanaxib doses are combined and the change from baseline is estimated using a mixed model-repeated measures approach with fixed factors for treatment, visit, log(baseline), treatment\visit, and log(baseline)\visit, subject is included as a random effect. The variance-covariance matrix is therefore not the same as in the three arm analysis, which causes treatment effects estimated in the placebo to group differ from those estimated in the analysis with three treatment arms.
Change in Liver Stiffness at Week 24 Compared to Screening, Where Setanaxib Doses Are Combined	Screening (Day -28) and Week 24	Change in liver stiffness at Week 24 compared to Screening, as assessed by transient elastography (FibroScan®). Setanaxib doses are combined and the change from baseline is estimated using a mixed model-repeated measures approach with fixed factors for treatment, visit, log(baseline), treatment\visit, and log(baseline)\visit, subject is included as a random effect. The variance-covariance matrix is therefore not the same as in the three arm analysis, which causes treatment effects estimated in the placebo to group differ from those estimated in the analysis with three treatment arms.

Trial Locations

Locations (127): Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Ordensklinikum Linz GmbH Barmherzige Schwestern
🇦🇹
Linz, Oberösterreich, Austria
ID Clinic
🇵🇱
Myslowice, Poland
Liver Specialists of Texas
🇺🇸
Houston, Texas, United States
Fiona Stanley Hospital
🇦🇺
Murdoch, Western Australia, Australia
Hospital Universitario de Canarias
🇪🇸
La Laguna, Santa Cruz De Tenerife, Spain
Icahn School of Medicine at Mount Sinai
🇺🇸
New York, New York, United States
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹
Milano, Italy
Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara
🇮🇹
Novara, Italy
Office Of Stephane M. Gauthier
🇨🇦
North Bay, Ontario, Canada
St. Joseph's Healthcare Hamilton - Charlton Campus
🇨🇦
Hamilton, Ontario, Canada
Centricity Research (LMC Manna Research) - London
🇨🇦
London, Ontario, Canada
William Osler Health System - Brampton Civic Hospital
🇨🇦
Brampton, Canada
University of Miami Leonard M. Miller School of Medicine
🇺🇸
Miami, Florida, United States
Northwestern University
🇺🇸
Evanston, Illinois, United States
Gastroenterology Associates - Crystal River
🇺🇸
Inverness, Florida, United States
Kansas Medical Clinic - Gastroenterology
🇺🇸
Topeka, Kansas, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
Einstein Medical Center
🇺🇸
Philadelphia, Pennsylvania, United States
Queen Elizabeth II Health Sciences Centre - Victoria General
🇨🇦
Halifax, Nova Scotia, Canada
Rapid City Medical Center
🇺🇸
Rapid City, South Dakota, United States
Monash Medical Centre
🇦🇺
Clayton, Victoria, Australia
Mater Misericordiae - Hospital Brisbane
🇦🇺
South Brisbane, Queensland, Australia
Dunedin Hospital
🇳🇿
Dunedin, New Zealand
University of Calgary
🇨🇦
Calgary, Alberta, Canada
Hospital General Universitario Gregorio Marañón
🇪🇸
Madrid, Spain
Hospital Germans Trias i Pujol
🇪🇸
Badalona, Barcelona, Spain
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
🇮🇹
Ancona, Italy
Hôpital l'Archet
🇫🇷
Nice, France
Waikato Hospital
🇳🇿
Hamilton, New Zealand
Tel Aviv Sourasky Medical Center
🇮🇱
Tel Aviv, Israel
Toronto Liver Center
🇨🇦
Toronto, Ontario, Canada
Hepato-Gastroenterologie HK
🇨🇿
Hradec Králové, Czechia
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico Humanitas
🇮🇹
Rozzano, Milan, Italy
Hospital Universitario Virgen de la Victoria
🇪🇸
Málaga, Spain
Rambam Health Care Campus
🇮🇱
Haifa, Israel
Hospital General Universitari d'Alicante
🇪🇸
Alicante, Spain
Azienda Ospedaliera Universitaria Policlinico Gaetano Martino
🇮🇹
Messina, Italy
Wellington Regional Hospital
🇳🇿
Crofton Downs, Wellington, New Zealand
Hospital Universitario La Paz
🇪🇸
Madrid, Spain
Ospedale San Giuseppe
🇮🇹
Milan, Milano, Italy
Università degli Studi di Napoli Federico II
🇮🇹
Napoli, Italy
Complejo Hospitalario Torrecárdenas
🇪🇸
Almería, Spain
Hospital Universitario Miguel Servet
🇪🇸
Zaragoza, Spain
Hadassah University Hospital Ein Kerem
🇮🇱
Jerusalem, Israel
Liverpool Hospital
🇦🇺
Liverpool, Australia
The Alfred Hospital
🇦🇺
Melbourne, Australia
Nepean Hospital
🇦🇺
Kingswood, Australia
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Vanderbilt Digestive Disease Center
🇺🇸
Nashville, Tennessee, United States
UA Thomas D. Boyer Liver Institute
🇺🇸
Tucson, Arizona, United States
California Liver Research Institute
🇺🇸
Pasadena, California, United States
University of California Davis Medical Center
🇺🇸
Sacramento, California, United States
Tampa General Hospital
🇺🇸
Tampa, Florida, United States
Summit - Southern Therapy and Advanced Research
🇺🇸
Jackson, Mississippi, United States
New York University Hepatology Associates
🇺🇸
New York, New York, United States
Pioneer Research Solutions
🇺🇸
Houston, Texas, United States
University of Utah Hospital
🇺🇸
Salt Lake City, Utah, United States
Froedtert and Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Universitaetsklinikum Graz - Universitätsklinik für Innere Medizin
🇦🇹
Graz, Styria, Austria
Hôpital Erasme
🇧🇪
Bruxelles, Brussels, Belgium
Centre Hospitalier de l'Université de Montréal (CHUM)
🇨🇦
Montréal, Quebec, Canada
Hôpital Claude Huriez
🇫🇷
Lille, France
Hôpitaux Universitaires Henri Mondor
🇫🇷
Créteil, Ile-de-France, France
Hopital Dupuytren
🇫🇷
Limoges, Limousin, France
Hôpitaux de Brabois
🇫🇷
Vandœuvre-lès-Nancy, Lorraine, France
Hôpital de la Croix Rousse
🇫🇷
Lyon, Rhone-alpes, France
Clinique Pasteur - Toulouse
🇫🇷
Toulouse, Occitanie, France
Centre Hosptitalier Universitaire d'Angers
🇫🇷
Angers, Pays De La Loire, France
Centre Hospitalier Universitaire Amiens-Picardie - Site Sud
🇫🇷
Amiens, Picardie, France
Hôpital Saint Joseph Marseille
🇫🇷
Marseille, France
Hôpital Saint-Antoine
🇫🇷
Paris, France
Klinikum rechts der Isar der Technischen Universität München
🇩🇪
Munich, Bayern, Germany
St. Josefs-Hospital Wiesbaden
🇩🇪
Wiesbaden, Hessen, Germany
Universitätsklinikum Frankfurt
🇩🇪
Frankfurt, Hessen, Germany
Medizinische Hochschule Hannover
🇩🇪
Hannover, Niedersachsen, Germany
Eugastro
🇩🇪
Leipzig, Sachsen, Germany
University General Hospital of Heraklion (PAGNI)
🇬🇷
Heraklion, Greece
Semmelweis Egyetem - I. Sz. Sebészeti és Intervenciós Gasztroenterológiai Klinika
🇭🇺
Budapest, Hungary
Carmel Medical Center
🇮🇱
Haifa, Haifa District, Israel
Western Galilee Hospital-Nahariya
🇮🇱
Nahariya, Northern District, Israel
Soroka Medical Center
🇮🇱
Be'er Sheva, Southern District, Israel
Rabin Medical Center - Beilinson Hospital
🇮🇱
Petah Tikva, Tel Aviv, Israel
Auckland City Hospital
🇳🇿
Grafton, Auckland, New Zealand
Szpital Specjalistyczny Nr 1 w Bytomiu
🇵🇱
Bytom, Poland
Centrum Badań Klinicznych Piotr Napora Lekarze Sp. p.
🇵🇱
Wrocław, Poland
Hospital del Mar - Parc de Salut Mar
🇪🇸
Barcelona, Spain
Hospital Universitario Reina Sofía
🇪🇸
Córdoba, Spain
Hospital Universitario de La Princesa
🇪🇸
Madrid, Spain
Hospital Clínico Universitario de Santiago
🇪🇸
Santiago, Spain
Akademiska Sjukhuset - Uppsala
🇸🇪
Uppsala, Sweden
Consorci Hospital General Universitari de València
🇪🇸
València, Spain
Hospital Universitario Virgen del Rocío
🇪🇸
Sevilla, Spain
King's College Hospital NHS Foundation Trust
🇬🇧
London, England, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧
Nottingham, England, United Kingdom
Springfield Clinic
🇺🇸
Springfield, Illinois, United States
John Hunter Hospital
🇦🇺
New Lambton Heights, New South Wales, Australia
Northwell Health
🇺🇸
Manhasset, New York, United States
Royal Prince Alfred Hospital
🇦🇺
Camperdown, New South Wales, Australia
Flinders Medical Centre
🇦🇺
Bedford Park, South Australia, Australia
Hospital de Sabadell
🇪🇸
Sabadell, Barcelona, Spain
Ústřední Vojenská Nemocnice Praha
🇨🇿
Praha, Prague, Czechia
Hospital Clínic de Barcelona
🇪🇸
Barcelona, Spain
Universitätsklinikum des Saarlandes
🇩🇪
Homburg, Germany
AdventHealth Transplant Institute
🇺🇸
Orlando, Florida, United States
Advanced Research Institute, Inc.
🇺🇸
Orlando, Florida, United States
A. Alfred Taubman Health Care Center
🇺🇸
Ann Arbor, Michigan, United States
Wake Forest University Baptist Medical Center
🇺🇸
Winston-Salem, North Carolina, United States
Kantonsspital Sankt Gallen
🇨🇭
Sankt Gallen, Switzerland
Universitair Ziekenhuis Gent
🇧🇪
Gent, Oost-Vlaanderen, Belgium
Azienda Socio Sanitaria Territoriale Monza - Ospedale San Gerardo
🇮🇹
Monza, Monza And Brianza, Italy
Klinikum Wels-Grieskirchen
🇦🇹
Wels, Oberösterreich, Austria
Universitair Ziekenhuis Leuven - Campus Gasthuisberg
🇧🇪
Leuven, Flemish Brabant, Belgium
Centre Hospitalier Universitaire Grenoble Alpes
🇫🇷
Grenoble, Isère, France
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
🇬🇧
Newcastle upon Tyne, England, United Kingdom
University General Hospital of Larissa
🇬🇷
Larissa, Greece
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Hôpital Rangueil
🇫🇷
Toulouse, Occitanie, France
Fondazione Epatocentro Ticino
🇨🇭
Lugano, Ticino, Switzerland
Centre Hospitalier Universitaire Brugmann - Site Victor Horta
🇧🇪
Laeken, Brussels, Belgium
Gloucestershire Hospitals NHS Foundation Trust
🇬🇧
Gloucester, England, United Kingdom
Eastern Health - Australia
🇦🇺
Box Hill, Victoria, Australia
University Hospital Southampton NHS Foundation Trust
🇬🇧
Southampton, England, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧
Sheffield, England, United Kingdom
Tulane Medical Center
🇺🇸
New Orleans, Louisiana, United States
NHS Greater Glasgow and Clyde
🇬🇧
Glasgow, Scotland, United Kingdom
Medizinische Universität Innsbruck
🇦🇹
Innsbruck, Tyrol, Austria