A Study Comparing the Efficacy and Safety of Etrolizumab to Infliximab in Participants With Moderate to Severe Ulcerative Colitis Who Are Naïve to Tumor Necrosis Factor (TNF) Inhibitors

Phase 3

Completed

Conditions: Ulcerative Colitis

Interventions: Drug: Etrolizumab
Drug: Infliximab
Other: Placebo (IV)
Other: Placebo (Injection)

Registration Number: NCT02136069

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This is a multicenter, Phase III, randomized, double-blind, double-dummy, parallel-group study to evaluate the safety, efficacy, and tolerability of etrolizumab compared with infliximab in treating participants with moderate to severe ulcerative colitis (UC) who are naive to tumor necrosis factor (TNF) inhibitors. Participants will be randomized in a 1:1 ratio to receive either etrolizumab 105 milligrams (mg) by subcutaneous (SC) injection once every 4 weeks (Q4W) + placebo (intravenous \[IV\] infusion at Weeks 0, 2, and 6, then once every 8 weeks \[Q8W\]) or infliximab 5 milligrams/kilogram (mg/kg) IV at Weeks 0, 2, and 6, then Q8W) + placebo (SC Q4W). Time on treatment is 54 weeks.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 397

Inclusion Criteria

Moderately to severely active UC as determined by the Mayo Clinic Score assessment (MCS)
Naive to treatment with any anti-TNF inhibitor therapy (including TNF inhibitor biosimilars)
An inadequate response to or intolerance of prior corticosteroid and/or immunosuppressant treatment
Background regimen for UC may include oral 5-aminosalicylate (5-ASA), oral corticosteroids, budenoside multi-matrix system (MMX), probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period
Use of highly effective contraception during and at least 24 weeks after the last dose of study drug

Exclusion Criteria

A history of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic, radiation or microscopic colitis, Crohn's disease, fistulas or abdominal abscesses, colonic mucosal dysplasia, intestinal obstruction, toxic megacolon, or unremoved adenomatous colonic polyps
Prior or planned surgery for UC
Past or present ileostomy or colostomy
Have received non-permitted inflammatory bowel disease (IBD) therapies (including natalizumab, vedolizumab, efalizumab, and tofactinib)
History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies; fusion proteins, or murine proteins; hypersensitivity to etrolizumab or any of its excipients
Chronic hepatitis B or C infection, Human deficiency virus (HIV) or tuberculosis (active or latent)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Etrolizumab + Placebo (IV)	Etrolizumab	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.
Etrolizumab + Placebo (IV)	Placebo (IV)	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.
Infliximab + Placebo (Injection)	Placebo (Injection)	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Infliximab + Placebo (Injection)	Infliximab	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS)	Week 10, Week 54	Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1. Clinical Remission is MCS ≤2 with individual subscores ≤1.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS	Week 54	Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1.
Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS	Week 10 and Week 54	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1.
Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS	Week 10 and Week 54	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.
Pharmacokinetics: Etrolizumab Serum Concentration	Weeks 2, 10, 12, 30, and 54
Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1	Week 10	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS	Week 54	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Endoscopic Remission is Endoscopy subscore = 0.
Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS	Week 10	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS	Baseline to Week 10	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS	Baseline to Week 54	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS	Baseline to Week 10, Week 54	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS	Week 10, Week 54	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.
Percentage of Participants That Achieve Clinical Remission Corticosteroid-Free at Week 54 (Off Corticosteroid for at Least 24 Weeks Prior to Week 54) Among Those Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS	Week 54	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1.
Number of Participants With Adverse Events Leading to Study Drug Discontinuation	Baseline until the end of study (up to 66 weeks)
Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0	Baseline until the end of study (up to 66 weeks)	All AEs were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Number of Participants With Serious Infection-Related Adverse Events	Baseline until the end of study (up to 66 weeks)
Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0	Baseline until the end of study (up to 66 weeks)	All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Number of Participants With Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)	Baseline until the end of study (up to 66 weeks)	All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Number of Participants With Malignancies	Baseline until the end of study (up to 66 weeks)
Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0	Baseline until the end of study (up to 66 weeks)	All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab	Weeks 0, 4, 10, 12, 30, and 54
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54	Weeks 10, 30, and 54	The IBDQ is used to assess participant's health-related quality of life (QOL). The 32-item questionnaire contains four domains: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). The items are scored on a 7-point Likert scale with a higher score indicating better health-related QOL. IBDQ score is a total score summed up from across all 32 questions on the questionnaire. The score can range from 32-224 and the higher score indicates a better quality of life.

Trial Locations

Locations (119): Chaim Sheba Medical Center; Pediatrics B North and Pediatric Endocrinology Unit
🇮🇱
Tel Hashomer, Israel
Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz es Szakrendelo
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Budapest, Hungary
Vasutegeszsegugyi Nonprofit KiemeltenKozhasznu Kft
🇭🇺
Debrecen, Hungary
Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza
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Bekescsaba, Hungary
Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz; II. Belgyogyaszat
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Miskolc, Hungary
Spitalul Clinic Colentina
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Bucharest, Romania
Singapore General Hospital
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Singapore, Singapore
Universitair Ziekenhuis Brussel; Neurology
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Bruxelles, Belgium
Imeldaziekenhuis
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Bonheiden, Belgium
CHU St Pierre (St Pierre)
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Brussels, Belgium
Amsterdam UMC Location VUMC
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Amsterdam, Netherlands
Azienda Ospedaliera San Camillo Forlanini
🇮🇹
Roma, Lazio, Italy
Maastricht University Medical Center
🇳🇱
Maastricht, Netherlands
Semmelweis Egyetem
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Budapest, Hungary
Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely
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Budapest, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
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Szeged, Hungary
King's College London
🇬🇧
London, United Kingdom
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
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Roma, Lazio, Italy
Radboudumc
🇳🇱
NL -nijmegen, Netherlands
S.C MedLife S.A
🇷🇴
Bucuresti, Romania
Spitalul Clinic Judetean Mures
🇷🇴
Targu Mures, Romania
Centrul Medical Unirea SRL
🇷🇴
Bucuresti, Romania
I.R.C.C.S Policlinico San Donato
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San Donato Milanese (MI), Lombardia, Italy
LKH - Universitätsklinikum der PMU Salzburg
🇦🇹
Salzburg, Austria
University of Calgary; Heritage Medical Research Clinic
🇨🇦
Calgary, Alberta, Canada
Zeidler Ledcor Centre - University of Alberta; Division of Gasroenterology
🇨🇦
Edmonton, Alberta, Canada
Vojenska nemocnice Brno
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Brno, Czechia
Mestska Nemocnice Ostrava
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Ostrava, Czechia
Pardubicka krajska nemocnice, a.s.
🇨🇿
Pardubice, Czechia
Guelph GI & Surgery Clinic
🇨🇦
Guelph, Ontario, Canada
GZA Ziekenhuizen - Campus Sint-Vincentius
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Antwerpen, Belgium
AZ Sint Elisabeth Herentals
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Herentals, Belgium
Centre de santé et de services sociaux Champlain-Charles-Le Moyne
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Greenfield Park, Quebec, Canada
Hôpital Maisonneuve - Rosemont
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Montreal, Quebec, Canada
Fakultni nemocnice Hradec Kralove
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Hradec Kralove, Czechia
ISCARE a.s.
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Praha 7, Czechia
Royal University Hospital
🇨🇦
Saskatoon, Saskatchewan, Canada
Cliniques Universitaires Saint-Luc; Pharmacy
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Bruxelles, Belgium
UZ Gent
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Gent, Belgium
CHU Tours - Hôpital Trousseau
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Chambray les Tours, France
CHU Clermont Ferrand - Hôtel Dieu
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Clermont-Ferrand, France
Hôpital Beaujon
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Clichy cedex, France
CHU de Caen - Hopital Cote de Nacre
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Caen, France
CHU Hopital Saint Eloi
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Montpellier, France
Centre Hospitalier Lyon Sud; Service de Gastro-Enterologie
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Pierre-Benite, France
Hôpital de Brabois Adultes
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Vandoeuvre-les-nancy, France
CHU Nice - Hopital de l'Archet 2
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Nice, France
Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
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Berlin, Germany
Universitätsklinikum Koeln
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Koeln, Germany
DRK Kliniken Berlin Westend
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Berlin, Germany
Universitätsklinikum Freiburg; Innere Medizin I; Hämatologie, Onkologie und Stammzelltransplantation
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Freiburg, Germany
Markhot Ferenc Oktato Korhaz es Rendelointezet
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Eger, Hungary
Asst Fatebenefratelli Sacco (Fatebenefratelli)
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Milano, Lombardia, Italy
Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
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Milano, Lombardia, Italy
Azienda Ospedaliero Universitaria di Parma
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Parma, Emilia-Romagna, Italy
Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
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Milano, Lombardia, Italy
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
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Székesfehérvár, Hungary
IRCCS Ospedale Casa Sollievo della Soffenza; Stru Comp di Gastroenterologia ed Endoscopia digest
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San Giovanni Rotondo, Lombardia, Italy
Ospedale Mauriziano Umberto I
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Torino, Piemonte, Italy
Rabin Medical Center-Beilinson Campus
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Petach Tikva, Israel
Azienda Ospedaliera Universitaria Careggi
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Firenze, Toscana, Italy
Azienda Ospedaliero Universitaria Pisana
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Pisa, Toscana, Italy
Dong-A University Hospital
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Busan, Korea, Republic of
Kyungpook National University Chilgok Hospital
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Daegu, Korea, Republic of
Addenbrooke's Hospital
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Cambridge, United Kingdom
Centrul de Gastroenterologie Dr. Goldis
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Timisoara, Romania
Royal Devon and Exeter Hospital (Wonford)
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Exeter, United Kingdom
Royal Victoria Infirmary
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Newcastle upon Tyne, United Kingdom
Fundacion Hospital de Alcorcon; Servicio de Digestivo
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Alcorcon, Madrid, Spain
Hospital da Senhora da Oliveira Guimarães
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Guimarães, Portugal
Institutul Clinic Fundeni Bucuresti
🇷🇴
Bucharest, Romania
Centro Médico Teknon
🇪🇸
Barcelona, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸
Valencia, Spain
The Royal Bournemouth Hospital
🇬🇧
Bournemouth, United Kingdom
Dr MJ Prins Practice
🇿🇦
Cape Town, South Africa
Dr Corne Kruger Inc.
🇿🇦
Cape Town, South Africa
Complejo Hospitalario Universitario de Ferrol
🇪🇸
Ferrol, LA Coruña, Spain
Netcare Universitas Private Hospital
🇿🇦
Bloemfontein, South Africa
Hospital Universitario de la Princesa
🇪🇸
Madrid, Spain
Akershus universitetssykehus HF
🇳🇴
Lørenskog, Norway
Fairfield General Hospital
🇬🇧
Manchester, United Kingdom
University Hospital Coventry
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Coventry, United Kingdom
Southampton General Hospital
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Southampton, United Kingdom
Hospital de Braga
🇵🇹
Braga, Portugal
Hospital Universitario La Paz
🇪🇸
Madrid, Spain
Inselspital-Universitaetsspital Bern
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Bern, Switzerland
Universitätsspital Zürich
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Zürich, Switzerland
Danderyds Sjukhus AB
🇸🇪
Stockholm, Sweden
St James University Hospital
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Leeds, United Kingdom
The Royal London Hospital
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London, United Kingdom
Nottingham University Hospitals NHS Trust
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Nottingham, United Kingdom
Korea University Ansan Hospital
🇰🇷
Gyeonggi-do, Korea, Republic of
Pusan National University Hospital
🇰🇷
Busan, Korea, Republic of
Yeungnam Univ. Hospital
🇰🇷
Daegu, Korea, Republic of
Universitaetsklinikum Schleswig-Holstein, Campus Kiel
🇩🇪
Kiel, Germany
Oblastni nemocnice Kladno, a.s., nemocnice Stredoces. kraje; Endoskopicke centrum
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Kladno, Czechia
Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z., Ocni oddeleni
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Usti Nad Labem, Czechia
St Thomas Hospital
🇬🇧
London, United Kingdom
Kyung Hee University Hospital
🇰🇷
Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
Krajska nemocnice T. Bati, a.s.
🇨🇿
Zlin, Czechia
Krankenhaus Waldfriede e. V.
🇩🇪
Berlin, Germany
Gastroenterologie Eppendorfer Baum
🇩🇪
Hamburg, Germany
Petz Aladar Megyei Oktato Korhaz
🇭🇺
Gyor, Hungary
Istituto Clinico Humanitas
🇮🇹
Rozzano (MI), Lombardia, Italy
Keimyung University Dongsan Medical Center
🇰🇷
Daegu, Korea, Republic of
Kyungpook National University Hospital
🇰🇷
Daegu, Korea, Republic of
CHA Bundang Medical Centre; CHA university
🇰🇷
Seongnam, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷
Seongnam-si, Korea, Republic of
Severance Hospital, Yonsei University
🇰🇷
Seoul, Korea, Republic of
Kangbuk Samsung Hospital
🇰🇷
Seoul, Korea, Republic of
Yonsei University Wonju Severance Christian Hospital
🇰🇷
Wonju-Si, Korea, Republic of
The Catholic University of Korea St. Vincent's Hospital
🇰🇷
Suwon-si,, Korea, Republic of
Ajou University Hospital
🇰🇷
Suwon City, Korea, Republic of
Amsterdam UMC Location AMC
🇳🇱
Amsterdam, Netherlands
Corporacio Sanitaria Parc Tauli
🇪🇸
Sabadell, Barcelona, Spain
Azienda Ospedaliera Di Padova
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Padova, Veneto, Italy