A Long Term Extension Trial of BI 655066/ABBV-066 (Risankizumab), in Patients With Moderately to Severely Active Crohn's Disease
- Conditions
- Crohn Disease
- Interventions
- Registration Number
- NCT02513459
- Lead Sponsor
- AbbVie
- Brief Summary
The primary objective of the study was to investigate long-term safety of risankizumab (BI 655066/ABBV-066) in participants with moderately to severely active Crohn's disease who showed a clinical response or remission on previous treatment with risankizumab in Study NCT02031276 (BI trial 1311.6/ AbbVie M15-993) and were now receiving long-term treatment. Additional objectives of this study were to further investigate long-term efficacy, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of risankizumab.
- Detailed Description
This was a single group, open-label long-term extension study that assessed the long-term safety, efficacy, and pharmacokinetics of risankizumab in participants with moderately to severely active Crohn's disease. This study was terminated early by AbbVie to enable participants who completed the study to rollover into Study NCT03105102 (AbbVie M16-000 Sub-Study 3 \[Phase 3 OLE study\]) for further OLE treatment within the Phase 3 program, which allows for risankizumab dose escalation if needed.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 65
-
Participants with Crohn's disease, who had successfully completed the preceding trial NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Successful treatment is defined as:
- Completion of period 2 in 1311.6 with a clinical response (drop in Crohn's Disease Activity Index (CDAI) from baseline by ≥100) but no remission (CDAI < 150) at Visit E1; or
- Completion of period 3 in 1311.6 with a clinical response (drop in CDAI from baseline by ≥100) and/or remission (CDAI < 150) at Visit E5; or
- Completion of period 2 or 3 in 1311.6 per protocol with a clinical response or remission before initiation of 1311.20 can roll-over either directly if that response/remission is maintained or through an open-label i.v. re-induction phase if they have lost their previous response/remission.
-
Female participants:
- Women of childbearing potential (not surgically sterilized and between menarche and 1 year postmenopause), that, if sexually active agree to use one of the appropriate medically accepted methods of birth control in addition to the consistent and correct use of a condom from date of screening until 20 weeks after last administration of study medication. Medically accepted methods of contraception are: ethinyl estradiol containing contraceptives, diaphragm with spermicide substance, and intrauterine device, or
- Surgically sterilized female participants with documentation of prior hysterectomy, tubal ligation or complete bilateral oophorectomy, or
- Postmenopausal women with postmenopausal is defined as permanent cessation >/=1 year of previously occurring menses, and
- Negative serum ß-Human Chorionic Gonadotrophin test at screening and urine pregnancy test prior to randomization.
-
Male participants:
- Who are documented to be sterile, or
- Who consistently and correctly use effective method of contraception (i.e. condoms) during the study and 20 weeks after last administration of study medication.
-
Be able to adhere to the study visit schedule and other protocol requirements.
- Participants who were not compliant with key study procedures (colonoscopy, treatment compliance, endpoint assessment, contraception measures) in preceding trial 1311.6
- Participants who could not tolerate risankizumab (BI 655066/ ABBV-066) treatment for tolerability or safety reasons in the preceding trial
- Are pregnant, nursing, or planning pregnancy while enrolled in the study, or within 20 weeks after receiving the last dose of study medication.
- Participants must agree not to receive a live virus or bacterial or Bacille Calmette-Guérin vaccination during the study or up to 12 months after the last administration of study drug.
- Participants who have developed malignancy, or suspicion of active malignant disease during the preceding trial
- Are intending to participate in any other study using an investigational agent or procedure during participation in this study.
- Cannot adhere to the concomitant medication requirements
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Risankizumab Risankizumab 600 mg IV Maintenance treatment with risankizumab 180 mg administered subcutaneously (SC) every 8 weeks (q8w) from Visit 2 through the end of trial (EOT) visit. Participants who re-gained their clinical response following the re-induction treatment could continue with maintenance treatment beginning at Visit 5. Risankizumab Risankizumab 180 mg SC Maintenance treatment with risankizumab 180 mg administered subcutaneously (SC) every 8 weeks (q8w) from Visit 2 through the end of trial (EOT) visit. Participants who re-gained their clinical response following the re-induction treatment could continue with maintenance treatment beginning at Visit 5.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events From the time of study drug administration until 140 days after the last dose of study drug in the current study or until the first dose of study drug in NCT03105102 (AbbVie M16-000 Sub-study 3), up to 4 years for participants who rolled-over A treatment emergent adverse event was defined as an event that occurred or worsened on or after the first dose of study drug through 140 days after the last dose in the current study for participants not rolling over into M16-000 Sub-study 3 or until the first dose of study drug in NCT03105102. All treatment-emergent serious and nonserious adverse events were collected, whether elicited or spontaneously reported by the participant.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Response by Visit Weeks 0, 24, 48, 72, 96, 120, 144, 168, and 192 The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). IBDQ response is defined as increase in IBDQ total score \>16 points from baseline. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993).
Mean Change From Baseline in Crohn's Disease Activity Index (CDAI) by Visit Weeks 0, 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104, 112, 120, 128, 136, 144, 152, 160, 168, 176, and 184 The Crohn's Disease Activity Index (CDAI) is a composite instrument that includes participant symptoms evaluated over 7 days (abdominal pain, stool frequency and general well-being), as well as physical and laboratory findings. These items are scored individually, weighted, and do not contribute equally to the overall score. The CDAI is derived from summing up the weighted individual scores of eight items. CDAI approximately ranges from 0 to 600 with higher scores indicating more severe disease. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). A negative change from baseline indicates improvement.
Mean Change From Baseline in Patient Reported Outcome 2 (PRO-2) Scores by Visit Weeks 0, 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104, 112, 120, 128, 136, 144, 152, 160, 168, 176, and 184 The PRO-2 is calculated based on the sum of the weighted patient-reported subscores of CDAI for liquid or soft stool frequency \[SF\] plus abdominal pain \[AP\] in the 7 days prior to the study visit. The PRO-2 score is calculated by adding the values of the summed stool frequency scores multiplied by 2 plus the summed abdominal pain scores multiplied by 5. The SF and AP score at an assessment visit was the average of the daily values reported during the 7 days preceding the scheduled assessment visit. PRO-2 scores range from 0 to no upper limit with higher scores indicating more severe disease. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). A negative change from baseline indicates improvement.
Percentage of Participants Achieving Crohn's Disease Endoscopic Index of Severity (CDEIS) Remission by Visit Weeks 0, 48, 104, 152, and 200 CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The score ranges from 0 to 44 where higher scores indicate more severe endoscopic activity. Remission is defined as a score of 4 or less, by visit (or for participants with initial isolated ileitis a score of 2 or less).
Mean Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Systemic System Domain Score by Visit Weeks 0, 24, 48, 72, 96, 120, 144, 168, and 192 The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Positive values indicate improvement from baseline.
Mean Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Social Function Domain Score by Visit Weeks 0, 24, 48, 72, 96, 120, 144, 168, and 192 The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Positive values indicate improvement from baseline.
Mean Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Emotional Function Domain Score by Visit Weeks 0, 24, 48, 72, 96, 120, 144, 168, and 192 The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Positive values indicate improvement from baseline.
Mean Change From Baseline in High-Sensitivity C-reactive Protein (Hs-CRP) by Visit Weeks 0, 8, 24, 40, 56, 72, 88, 104, 120, 128, 136, 152, 160, 176, and 184 Concentration of serum high-sensitivity C-reactive Protein (hs-CRP) was analyzed by a central laboratory. It is a general marker of inflammation that is sensitive to acute changes in inflammatory response, and higher levels indicate more inflammation. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Negative values indicate improvement from baseline.
Mean Change From Baseline in Fecal Calprotectin (FCP) Profile by Visit Weeks 0, 24, 56, 88, 120, 152, and 184 Fecal calprotectin (FCP) is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. Stool samples were analyzed by a central laboratory for fecal calprotectin levels. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Negative values indicate improvement from baseline.
Percentage of Participants Achieving Crohn's Disease Activity Index (CDAI) Clinical Remission by Visit Weeks 0, 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104, 112, 120, 128, 136, 144, 152, 160, 168, 176, and 184 The Crohn's Disease Activity Index (CDAI) is a composite instrument that includes participant symptoms evaluated over 7 days (abdominal pain, stool frequency and general well-being), as well as physical and laboratory findings. These items are scored individually, weighted, and do not contribute equally to the overall score. The CDAI is derived from summing up the weighted individual scores of eight items. CDAI approximately ranges from 0 to 600 with higher scores indicating more severe disease. Clinical remission is defined as CDAI score \< 150.
Percentage of Participants Achieving Crohn's Disease Activity Index (CDAI) Clinical Response by Visit Weeks 0, 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104, 112, 120, 128, 136, 144, 152, 160, 168, 176, and 184 The Crohn's Disease Activity Index (CDAI) is a composite instrument that includes participant symptoms evaluated over 7 days (abdominal pain, stool frequency and general well-being), as well as physical and laboratory findings. These items are scored individually, weighted, and do not contribute equally to the overall score. The CDAI is derived from summing up the weighted individual scores of eight items. CDAI approximately ranges from 0 to 600 with higher scores indicating more severe disease. Clinical response is defined as CDAI score \< 150 or a reduction from baseline of at least 100 points. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993).
Percentage of Participants Achieving Patient Reported Outcome 2 (PRO-2) Remission by Visit Weeks 0, 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104, 112, 120, 128, 136, 144, 152, 160, 168, 176, and 184 The PRO-2 is calculated based on the sum of the weighted patient-reported subscores of CDAI for liquid or soft stool frequency \[SF\] plus abdominal pain \[AP\] in the 7 days prior to the study visit. The PRO-2 score is calculated by adding the values of the summed stool frequency scores multiplied by 2 plus the summed abdominal pain scores multiplied by 5. The SF and AP score at an assessment visit was the average of the daily values reported during the 7 days preceding the scheduled assessment visit. PRO-2 scores range from 0 to no upper limit with higher scores indicating more severe disease. Remission is defined as PRO-2 score \< 75.
Percentage of Participants Achieving Crohn's Disease Endoscopic Index of Severity (CDEIS) Response by Visit Weeks 0, 48, 104, 152, and 200 CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The score ranges from 0 to 44 where higher scores indicate more severe endoscopic activity. Response is defined as a score of 7 or less (or for participants with initial isolated ileitis \> 50% reduction from baseline). Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993).
Percentage of Participants With Mucosal Healing by Visit Weeks 0, 48, 104, 152, and 200 Mucosal healing is defined as Crohn's Disease Endoscopy Index of Severity (CDEIS) ulcerations sub-score (deep ulceration, superficial ulceration, ulcerated stenosis) of 0 as evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The overall CDEIS score ranges from 0 to 44 where higher scores indicate more severe endoscopic activity.
Percentage of Participants Achieving Deep Remission by Visit Weeks 0, 48, 104, 152, and 200 Deep remission is defined as clinical remission (CDAI \< 150) and CDEIS remission (CDEIS score of 4 or less, by visit or for participants with initial isolated ileitis a score of 2 or less).
Percentage of Participants Achieving Patient Reported Outcome 2 (PRO-2) Response by Visit Weeks 0, 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104, 112, 120, 128, 136, 144, 152, 160, 168, 176, and 184 The PRO-2 is calculated based on the sum of the weighted patient-reported subscores of CDAI for liquid or soft stool frequency \[SF\] plus abdominal pain \[AP\] in the 7 days prior to the study visit. The PRO-2 score is calculated by adding the values of the summed stool frequency scores multiplied by 2 plus the summed abdominal pain scores multiplied by 5. The SF and AP score at an assessment visit was the average of the daily values reported during the 7 days preceding the scheduled assessment visit. PRO-2 scores range from 0 to no upper limit with higher scores indicating more severe disease. PRO-2 response is defined as a decrease from baseline of 50 points or more. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993).
Mean Change From Baseline in Crohn's Disease Endoscopic Index of Severity (CDEIS) by Visit Weeks 0, 48, 104, 152, and 200 CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The score ranges from 0 to 44 where higher scores indicate more severe endoscopic activity. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). A negative change from baseline indicates improvement.
Mean Change From Baseline in Simple Endoscopic Score (SES-CD) by Visit Weeks 0, 48, 104, 152, and 200 SES-CD is calculated based the sum of individual segment values for four endoscopic variables (presence and size of ulcers, ulcerated surface, affected surface and presence of narrowing). Each variable in each segment is scored 0 to 3 resulting in SES-CD values ranging from 0 to 56 with higher scores indicating more severe disease. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). A negative change from baseline indicates improvement.
Mean Change From Baseline in Stool Frequency (SF) By Visit Weeks 0, 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104, 112, 120, 128, 136, 144, 152, 160, 168, 176, and 184 Participants were asked to record the frequency of liquid stools on a daily basis. The number of liquid stools in the prior 7 days was summed. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Negative values indicate improvement from baseline.
Mean Change From Baseline in Abdominal Pain (AP) Score By Visit Weeks 0, 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104, 112, 120, 128, 136, 144, 152, 160, 168, 176, and 184 Participants were asked to rate and record daily abdominal pain on a scale of 0 to 3 \[none (0), mild (1), moderate (2) and severe (3)\]. The ratings in the prior 7 days were summed. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Negative values indicate improvement from baseline.
Mean Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score by Visit Weeks 0, 24, 48, 72, 96, 120, 144, 168, and 192 The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Positive values indicate improvement from baseline.
Mean Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom Domain Score by Visit Weeks 0, 24, 48, 72, 96, 120, 144, 168, and 192 The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Positive values indicate improvement from baseline.
Percentage of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Remission by Visit Weeks 0, 24, 48, 72, 96, 120, 144, 168, and 192 The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). IBDQ remission is defined as IBDQ total score \> 170 points.
Trial Locations
- Locations (28)
AZ-Delta /ID# 154983
🇧🇪Roeselare, Belgium
MGG Group, Inc.Chevy Chase Clinical Research /ID# 155068
🇺🇸Chevy Chase, Maryland, United States
Hospital Univ de la Princesa /ID# 155065
🇪🇸Madrid, Spain
Clin Res Inst of Michigan, LLC /ID# 155066
🇺🇸Chesterfield, Michigan, United States
Yeungnam University Med Ctr /ID# 155056
🇰🇷Daegu, Daegu Gwang Yeogsi, Korea, Republic of
NZOZ Vivamed /ID# 155061
🇵🇱Warsaw, Poland
Imelda Ziekenhuis /ID# 154984
🇧🇪Bonheiden, Belgium
ULB Erasme /ID# 154987
🇧🇪Brussels, Belgium
Universitaetsklinikum Erlangen /ID# 155039
🇩🇪Erlangen, Bayern, Germany
Med Hochschule Hanover /ID# 155041
🇩🇪Hannover, Germany
Cliniques Universitaires Saint Luc /ID# 154985
🇧🇪Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium
UZ Leuven /ID# 154986
🇧🇪Leuven, Belgium
McMaster University Med Cent /ID# 155019
🇨🇦Hamilton, Ontario, Canada
Maastricht Universitair Medisch Centrum /ID# 155059
🇳🇱Maastricht, Netherlands
Addenbrookes Hospital /ID# 155047
🇬🇧Cambridge, United Kingdom
Hospital Clinic de Barcelona /ID# 155064
🇪🇸Barcelona, Spain
Hospital Duran i Reynals /ID# 155063
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
John Radcliffe Hospital /ID# 155048
🇬🇧Oxford, United Kingdom
Lexmedica /Id# 155062
🇵🇱Wroclaw, Poland
CHU de Liege /ID# 154988
🇧🇪Liège, Liege, Belgium
Kangbuk Samsung Hospital /ID# 155054
🇰🇷Jongno-Gu, Seoul Teugbyeolsi, Korea, Republic of
AZ Groeninge /ID# 154989
🇧🇪Kortrijk, Belgium
Severance Hospital /ID# 155055
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Academisch Medisch Centrum /ID# 155058
🇳🇱Amsterdam, Noord-Holland, Netherlands
Asan Medical Center /ID# 155053
🇰🇷Seoul, Korea, Republic of
Guy's and St Thomas' NHS Found /ID# 155046
🇬🇧London, London, City Of, United Kingdom
St. James University Hospital /ID# 155050
🇬🇧Leeds, United Kingdom
The Newcastle Upon Tyne Hospitals NHS Foundation Trust' /ID# 155049
🇬🇧Newcastle Upon Tyne, United Kingdom