MedPath

Study to Evaluate the Safety and Efficacy of Two Adalimumab Dosing Regimens in Subjects With Moderate to Severe Ulcerative Colitis

Phase 3
Completed
Conditions
Ulcerative Colitis (UC)
Interventions
Other: Placebo
Registration Number
NCT02065622
Lead Sponsor
AbbVie
Brief Summary

To evaluate safety and efficacy of two adalimumab dosing regimens for induction and maintenance (standard and higher dosing) in achieving clinical remission in subjects with moderately to severely active ulcerative colitis.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
952
Inclusion Criteria
  • Diagnosis of Ulcerative Colitis (UC) for at least 90 days, confirmed by endoscopy during Screening period.
  • Active UC with Mayo Score of 6 to 12 points and endoscopy subscore of 2 to 3 despite concurrent or prior treatment with a full and adequate course, in the opinion of the Investigator, with oral corticosteroids or immunosuppressants or both. Mayo Score is confirmed by central reader.
Exclusion Criteria
  • Subject with Crohn's disease (CD) or indeterminate colitis (IC).
  • Current diagnosis of fulminant colitis and/or toxic megacolon.
  • Subjects with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy.
  • Chronic recurring infections or active tuberculosis (TB).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Induction (Main Study + Japan Sub-study): I-SDPlaceboInduction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Maintenance (Main Study + Japan Sub-study): M-SDPlaceboMaintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance (Main Study): TDM RegimenPlaceboDouble-blind adalimumab 40 mg eow at Week 8 and Week 10, with possible dose adjustments at Weeks 12, 24, and 37 based on criteria assessing blinded adalimumab serum concentration and rectal bleeding subscore (RBS) assessments.
Induction (Main Study + Japan Sub-study): I-SDAdalimumabInduction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Maintenance (Main Study + Japan Sub-study): M-SDAdalimumabMaintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Induction (Main Study + Japan Sub-study): I-HDAdalimumabInduction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4, and 40 mg at Week 6.
Maintenance (Main Study): TDM RegimenAdalimumabDouble-blind adalimumab 40 mg eow at Week 8 and Week 10, with possible dose adjustments at Weeks 12, 24, and 37 based on criteria assessing blinded adalimumab serum concentration and rectal bleeding subscore (RBS) assessments.
Maintenance (Main Study + Japan Sub-study): M-HDAdalimumabMaintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Primary Outcome Measures
NameTimeMethod
Maintenance Period Primary Endpoint: Percentage of Week 8 Responders (Per FMS) With Clinical Remission (Per FMS) at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders (per FMS) are defined as participants with a decrease in Full Mayo score of ≥ 3 points and ≥ 30% from Baseline plus a decrease from baseline in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore \> 1.

Induction Period Primary Endpoint: Percentage of Participants With Clinical Remission Per Full Mayo Score (FMS) at Week 8Week 8

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore \> 1.

Secondary Outcome Measures
NameTimeMethod
Induction Period Ranked Secondary Endpoint 1: Percentage of Participants With Endoscopic Improvement at Week 8Week 8

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1.

Induction Period Ranked Secondary Endpoint 4: Percentage of Participants With Clinical Response Per FMS at Week 8Week 8

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical response is defined as a decrease in FMS of ≥ 3 points and ≥ 30% from baseline, plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1.

Induction Period Ranked Secondary Endpoint 7: Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 8Week 8

The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The IBDQ Fatigue item score range is from 1 (severe problem) to 7 (normal health). Response is defined as an increase of IBDQ Fatigue item score ≥ 1.

Induction Period Ranked Secondary Endpoint 6: Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 8Week 8

The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The range for Bowel Symptom domain score is 10 (severe problem) to 70 (normal health). Response in IBDQ Bowel Symptom domain is defined as an increase of IBDQ Bowel Symptom domain score ≥ 6.

Maintenance Period Ranked Secondary Endpoint 1: Percentage of Week 8 Responders (Per FMS) With Endoscopic Improvement at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1.

Maintenance Period Ranked Secondary Endpoint 3: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders, per FMS, are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Clinical remission is defined as FMS ≤ 2 with no subscore \> 1.

Maintenance Period Ranked Secondary Endpoint 2: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders, per FMS, are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1.

Maintenance Period Ranked Secondary Endpoint 5: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Improvement at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1. Endoscopy subscore provided by the central reader.

Maintenance Period Ranked Secondary Endpoint 6: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1.

Maintenance Period Ranked Secondary Endpoint 7: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission (Per FMS) at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1.

Maintenance Period Ranked Secondary Endpoint 8: Percentage of Week 8 Responders (Per FMS) With IBDQ Response (Increase of IBDQ ≥ 16 From Baseline) at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Total IBDQ score is the sum of responses to the individual IBDQ questions, and ranges from 32 to 224 with higher scores indicating a better quality of life.

Induction Period Ranked Secondary Endpoint 2: Percentage of Participants With Fecal Calprotectin < 150 mg/kg at Week 8Week 8
Maintenance Period Ranked Secondary Endpoint 9: Percentage of Week 8 Non-Responders With Clinical Remission (Per FMS) at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 non-responders are defined as participants not meeting the criteria of response (defined as a decrease in FMS of ≥ 3 points and ≥ 30% from baseline, plus a decrease in the rectal bleeding subscore \[RBS\] ≥ 1 or an absolute RBS ≤ 1) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1.

Maintenance Period Ranked Secondary Endpoint 10: Percentage of Week 8 Non-Remitters With Clinical Remission (Per FMS) at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 non-remitters are defined as participants not meeting the criteria of clinical remission at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1.

Maintenance Period Ranked Secondary Endpoint 11: Percentage of Week 8 Responders (Per FMS) With Endoscopic Subscore of 0 at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders (per Full Mayo score) are defined as participants with a decrease in Full Mayo score of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Endoscopic remission is defined as an endoscopy subscore of 0.

Maintenance Period Ranked Secondary Endpoint 12: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Subscore of 0 at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. Endoscopic remission is defined as an endoscopy subscore of 0.

Maintenance Period Ranked Secondary Endpoint 13: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Bowel Symptom Domain at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore \[RBS\] ≥ 1 or an absolute RBS ≤ 1. The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Bowel Symptom domain score range is 10 (severe problem) to 70 (normal health). Response is defined as increase of Bowel Symptom domain score ≥ 6 from baseline.

Maintenance Period Ranked Secondary Endpoint 14: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Fatigue Item at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Response in IBDQ fatigue item (range 1 \[severe problem\] to 7 \[normal health\]) is defined as increase of IBDQ fatigue item ≥ 1 from baseline.

Induction Period Ranked Secondary Endpoint 3: Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response (Increase of IBDQ ≥ 16 From Baseline) at Week 8Week 8

The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Total IBDQ score is the sum of the responses to the individual IBDQ questions, and ranges from 32 to 224 with higher scores indicating a better quality of life.

Induction Period Ranked Secondary Endpoint 5: Percentage of Participants With Endoscopic Remission at Week 8Week 8

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Endoscopic remission is defined as an endoscopy subscore of 0.

Maintenance Period Ranked Secondary Endpoint 4: Percentage of Week 8 Remitters (Per FMS) With Clinical Remission (Per FMS) at Week 52Week 52

The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. Endoscopy subscore provided by the central reader.

Trial Locations

Locations (173)

Atlanta Gastro Assoc /ID# 122336

🇺🇸

Atlanta, Georgia, United States

Northwestern University Feinberg School of Medicine /ID# 122183

🇺🇸

Chicago, Illinois, United States

University of Pittsburgh MC /ID# 122331

🇺🇸

Pittsburgh, Pennsylvania, United States

Biopharma Informatic Research /ID# 171150

🇺🇸

Houston, Texas, United States

Research Associates of South Florida,LLC /ID# 170309

🇺🇸

Miami, Florida, United States

New River Valley Research Inst /ID# 127801

🇺🇸

Christiansburg, Virginia, United States

Consultants for Clinical Res /ID# 122304

🇺🇸

Cincinnati, Ohio, United States

Gastro United of Tulsa /ID# 125436

🇺🇸

Tulsa, Oklahoma, United States

Icahn School of Med Mt. Sinai /ID# 127047

🇺🇸

New York, New York, United States

University of Washington /ID# 169721

🇺🇸

Seattle, Washington, United States

Charlotte Gastro Hepatology /ID# 122235

🇺🇸

Charlotte, North Carolina, United States

Texas Digestive Disease Consul /ID# 141677

🇺🇸

Southlake, Texas, United States

Gastro One /ID# 122339

🇺🇸

Germantown, Tennessee, United States

NYU Langone Long Island CRA /ID# 122177

🇺🇸

Great Neck, New York, United States

Dayton Gastroenterology, Inc. /ID# 127804

🇺🇸

Englewood, Ohio, United States

DHAT Research Institute /ID# 170616

🇺🇸

Garland, Texas, United States

Austin Center for Clinical Research /ID# 125396

🇺🇸

Pflugerville, Texas, United States

Universitaetsklinik fuer Innere Medizin 1 /ID# 125944

🇦🇹

Salzburg, Austria

Universitatsklinikum Magdeburg /ID# 127200

🇩🇪

Magdeburg, Germany

University of Calgary /ID# 125715

🇨🇦

Calgary, Alberta, Canada

KH der Barmherzigen Brueder /ID# 127183

🇦🇹

St Veit An Der Glan, Austria

CHU de Liege /ID# 126740

🇧🇪

Liege, Belgium

Universita di Padova /ID# 127214

🇮🇹

Padova, Italy

CHU de Grenoble - Albet Michal /ID# 127195

🇫🇷

Grenoble, France

Tel Aviv Sourasky Medical Center /ID# 201365

🇮🇱

Tel Aviv-Yafo, Tel-Aviv, Israel

Universitatsklinik Regensburg /ID# 201265

🇩🇪

Ratisbon, Bayern, Germany

Universitatsklinikum Frankfurt /ID# 170300

🇩🇪

Frankfurt, Hessen, Germany

AZ Sint-Lucas /ID# 127187

🇧🇪

Ghent, Belgium

UZ Leuven /ID# 126739

🇧🇪

Leuven, Belgium

Texas Digestive Disease Consul /ID# 141678

🇺🇸

Southlake, Texas, United States

McGill Univ HC /ID# 127046

🇨🇦

Montreal, Quebec, Canada

Winnipeg Regional Health Autho /ID# 125712

🇨🇦

Winnipeg, Manitoba, Canada

ISCARE a.s. /ID# 127837

🇨🇿

Praha 9, Czechia

Medizinische Universitat Wien /ID# 127186

🇦🇹

Vienna, Wien, Austria

Pecsi Tudomanyegyetem Klinikai Kozpont I. sz. Belgyogyaszati Klinika /ID# 127209

🇭🇺

Pécs, Pecs, Hungary

Soroka University Medical Center /ID# 127213

🇮🇱

Be'er Sheva, Israel

Policlinico Agostino Gemelli /ID# 127217

🇮🇹

Rome, Lazio, Italy

Mount Sinai Hosp.-Toronto /ID# 126590

🇨🇦

Toronto, Ontario, Canada

London Health Sciences Centre /ID# 127055

🇨🇦

London, Ontario, Canada

Azienda Ospedaliera San Camillo Forlanini /ID# 127216

🇮🇹

Rome, Lazio, Italy

Hadassah University Hospital /ID# 127211

🇮🇱

Jerusalem, Israel

Hepato-Gastroenterologie HK s.r.o. /ID# 127188

🇨🇿

Hradec Kralove, Czechia

Universitaetsklinikum Jena /ID# 127205

🇩🇪

Jena, Germany

Hopital Rangueil /ID# 127192

🇫🇷

Toulouse, France

Asklepios Westklinikum Hamburg /ID# 127198

🇩🇪

Hamburg, Germany

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 127138

🇮🇹

Milan, Lombardia, Italy

IRCCS Casa Sollievo /ID# 127811

🇮🇹

San Giovanni Rotondo, Italy

EUGASTRO GmbH /ID# 127202

🇩🇪

Leipzig, Germany

Pannonia Maganorvosi Centrum Kft. /ID# 127207

🇭🇺

Budapest, Hungary

Policlinico Univ Tor Vergata /ID# 129321

🇮🇹

Rome, Italy

Hiroshima University Hospital /ID# 124496

🇯🇵

Hiroshima-shi, Hiroshima, Japan

Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital /ID# 124480

🇯🇵

Sapporo-shi, Hokkaido, Japan

Hamamatsu South Hospital /ID# 124481

🇯🇵

Hamamatsu-shi, Shizuoka, Japan

Shiga University of Medical Science Hospital /ID# 127675

🇯🇵

Otsu-shi, Shiga, Japan

Saitama Medical Center /ID# 128875

🇯🇵

Kawagoe-shi, Saitama, Japan

Southampton General Hospital /ID# 127228

🇬🇧

Southampton, United Kingdom

Hospital Clinic de Barcelona /ID# 138147

🇪🇸

Barcelona, Spain

CHU NANCY - Hôpital Brabois Adultes /ID# 127196

🇫🇷

Vandoeuvre les Nancy CEDEX, Meurthe-et-Moselle, France

Univ Hosp Schleswig-Holstein, Campus Kiel, Klinik furer Innere Medizin /ID# 127199

🇩🇪

Kiel, Schleswig-Holstein, Germany

Vanderbilt Univ Med Ctr /ID# 125496

🇺🇸

Nashville, Tennessee, United States

University of Utah /ID# 122333

🇺🇸

Salt Lake City, Utah, United States

Herlev Hospital /ID# 127191

🇩🇰

Herlev, Hovedstaden, Denmark

Regionhospital Silkeborg /ID# 127190

🇩🇰

Silkeborg, Denmark

CHU Estaing /ID# 127848

🇫🇷

Clermont Ferrand, France

CHU Saint ELOI /ID# 169007

🇫🇷

Montpellier Cedex 5, France

Mayo Clinic - Rochester /ID# 122244

🇺🇸

Rochester, Minnesota, United States

WI Center for Advanced Res /ID# 122178

🇺🇸

Milwaukee, Wisconsin, United States

The Oregon Clinic- Gastro West /ID# 135273

🇺🇸

Portland, Oregon, United States

Froedtert & the Medical College of Wisconsin /ID# 122261

🇺🇸

Milwaukee, Wisconsin, United States

Kaplan Medical Center /ID# 127210

🇮🇱

Rehovot, Israel

Digestive Health Specialists of the Southeast /ID# 127844

🇺🇸

Dothan, Alabama, United States

Gastroenterology Group Naples /ID# 127806

🇺🇸

Naples, Florida, United States

Shafran Gastroenterology Ctr /ID# 122320

🇺🇸

Winter Park, Florida, United States

Ucsd /Id# 122313

🇺🇸

La Jolla, California, United States

Rocky Mountain Clinical Resear /ID# 122180

🇺🇸

Wheat Ridge, Colorado, United States

Medical Research Ctr CT /ID# 122179

🇺🇸

Hamden, Connecticut, United States

Gastro Florida /ID# 170619

🇺🇸

Clearwater, Florida, United States

Gastro Assoc of Central GA /ID# 122318

🇺🇸

Macon, Georgia, United States

Carle Foundation Hospital /ID# 135955

🇺🇸

Urbana, Illinois, United States

University of Chicago /ID# 122302

🇺🇸

Chicago, Illinois, United States

University of Maryland Med Ctr /ID# 169734

🇺🇸

Baltimore, Maryland, United States

Louisiana Research Ctr. LLC /ID# 141655

🇺🇸

Shreveport, Louisiana, United States

MGG Group, Inc.Chevy Chase Clinical Research /ID# 122238

🇺🇸

Chevy Chase, Maryland, United States

Ctr for Digest and Liver Dis /ID# 122182

🇺🇸

Mexico, Missouri, United States

Wake Research Associates, LLC /ID# 122157

🇺🇸

Raleigh, North Carolina, United States

Erlanger Institute for Clinica /ID# 129009

🇺🇸

Chattanooga, Tennessee, United States

Advanced Research Institute /ID# 126147

🇺🇸

Ogden, Utah, United States

KH der Elisabethinen Linz GmbH /ID# 127184

🇦🇹

Linz, Oberoesterreich, Austria

Zeidler Ledcor Centre /ID# 125713

🇨🇦

Edmonton, Alberta, Canada

Qe Ii Hsc /Id# 127045

🇨🇦

Halifax, Nova Scotia, Canada

Toronto Digestive Disease Asso /ID# 127075

🇨🇦

Vaughan, Ontario, Canada

CHU Dijon /ID# 127861

🇫🇷

Dijon, France

CHU de Saint-Etienne, Hopital Nord /ID# 134490

🇫🇷

SAINT-ETIENNE Cedex 1, France

CHU de Nice /ID# 127193

🇫🇷

Nice, France

Mross, Berlin, DE /ID# 127201

🇩🇪

Berlin, Germany

Gastrostudien GbR /ID# 169246

🇩🇪

Berlin, Germany

Gastro Campus Research GbR /ID# 126743

🇩🇪

Munster, Germany

Szegedi Tudomanyegyetem /ID# 127208

🇭🇺

Szeged, Hungary

A.O.U. Policlinico S.Orsola-Malpighi /ID# 129322

🇮🇹

Bologna, Emilia-Romagna, Italy

Rabin Medical Center /ID# 127212

🇮🇱

Petakh Tikva, Tel-Aviv, Israel

Ospedali Riuniti Villa Sofia-C /ID# 129323

🇮🇹

Palermo, Italy

Azienda Ospedaliera Spedali Civili /ID# 127236

🇮🇹

Brescia, Italy

IBD Center - IRCCS Istituto Clinico Humanitas /ID# 127215

🇮🇹

Rozzano, Milano, Italy

Nagoya City University Hospital /ID# 124517

🇯🇵

Nagoya-shi, Aichi, Japan

Yokoyama IBD Clinic /ID# 151560

🇯🇵

Nagoya, Aichi, Japan

Toho University Sakura Medical Center /ID# 124497

🇯🇵

Sakura-shi, Chiba, Japan

Kyushu University Hospital /ID# 124495

🇯🇵

Fukuoka-shi, Fukuoka, Japan

Fukuoka University Chikushi Hospital /ID# 124155

🇯🇵

Chikushino, Fukuoka, Japan

Kurume University Hospital /ID# 125275

🇯🇵

Kurume-shi, Fukuoka, Japan

Aoyama Clinic /ID# 127836

🇯🇵

Kobe-shi, Hyogo, Japan

Hyogo College of Medicine College Hospital /Id# 127539

🇯🇵

Nishinomiya-shi, Hyogo, Japan

Kitasato University Hospital /ID# 137694

🇯🇵

Sagamihara-shi, Kanagawa, Japan

COLO-PROCTOLOGY CENTER Matsushima Clinic /ID# 148423

🇯🇵

Yokohama, Kanagawa, Japan

Susaki Kuroshio Hospital /ID# 125202

🇯🇵

Susaki-shi, Kochi, Japan

Japanese Red Cross Kyoto Daiichi Hos /ID# 127540

🇯🇵

Kyoto-shi, Kyoto, Japan

Osaka Medical College Hospital /ID# 126451

🇯🇵

Takatsuki-shi, Osaka, Japan

Kitasato Univ Kitasato Inst Ho /ID# 127001

🇯🇵

Minato-ku, Tokyo, Japan

Kyorin University Hospital /ID# 148184

🇯🇵

Mitaka-shi, Tokyo, Japan

Tokyo Yamate Medical Center /ID# 125201

🇯🇵

Tokyo, Japan

Wakayama Medical University /ID# 124635

🇯🇵

Wakayama-shi, Wakayama, Japan

Endoterapia PFG Sp. z.o.o. /ID# 126513

🇵🇱

Warszawa, Mazowieckie, Poland

Academisch Medisch Centrum /ID# 126741

🇳🇱

Amsterdam, Noord-Holland, Netherlands

Centrum Medyczne Pratia Gdynia /ID# 170301

🇵🇱

Gdynia, Pomorskie, Poland

H-T.Centrum Medyczne-Endoterapia /ID# 170305

🇵🇱

Tychy, Slaskie, Poland

Centrum Medyczne Sw. Lukaza /ID# 126515

🇵🇱

Czestochowa, Poland

Centrum Diagnostyczno Lecznicze Barska /ID# 170304

🇵🇱

Lodz, Poland

KO-Med Centra Kliniczne Pulawy /ID# 127219

🇵🇱

Pulawy, Poland

NZOZ Vivamed /ID# 127218

🇵🇱

Warsaw, Poland

Institutul Clinic Fundeni /ID# 127839

🇷🇴

Sector 2, Bucuresti, Romania

Spitalul Clinic Judetean de Urgenta /ID# 125418

🇷🇴

Cluj, Romania

CMDTA Neomed SRL /ID# 127142

🇷🇴

Brasov, Romania

Tvm Med Serv Srl /Id# 127221

🇷🇴

Cluj, Romania

Gastroenterologicke centrum ASSIDUO a IBD centrum /ID# 127222

🇸🇰

Bratislava, Slovakia

Cabinet Medical Dr. Fratila SRL, Specialitatea Medicina Interna /ID# 127002

🇷🇴

Oradea, Romania

Salvo-San-Ciobanca SRL /ID# 127140

🇷🇴

Zalau, Romania

Hospital General Universitario de Alicante /ID# 129261

🇪🇸

Alicante, Spain

Hospital General Universitario Gregorio Maranon /ID# 127224

🇪🇸

Madrid, Spain

Hospital Univ de la Princesa /ID# 135828

🇪🇸

Madrid, Spain

Complejo Hospitalario Universitario de Ferrol /ID# 127840

🇪🇸

Ferrol, Spain

Hospital Univ Dr. Negrin /ID# 127841

🇪🇸

Las Palmas de Gran Canaria, Spain

Hosp Univ 12 de Octubre /ID# 129257

🇪🇸

Madrid, Spain

Hosp Clin Univ de Valencia /ID# 170306

🇪🇸

València, Spain

Hosp Clin Univ Lozano Blesa /ID# 129255

🇪🇸

Zaragoza, Spain

Hospital Universitario La Paz /ID# 127223

🇪🇸

Madrid, Spain

University Hospital Zurich /ID# 127842

🇨🇭

Zurich, Zuerich, Switzerland

Kantonsspital St. Gallen /ID# 127843

🇨🇭

St. Gallen, Sankt Gallen, Switzerland

GI National Institute of Therapy named by L.T. Malaya /ID# 127231

🇺🇦

Kharkiv, Kharkivska Oblast, Ukraine

St. Mark's Hospital /ID# 127226

🇬🇧

Harrow, United Kingdom

Western General Hospital /ID# 204801

🇬🇧

Edinburgh, United Kingdom

Hull and East Yorkshire Hospitals NHS Trust /ID# 127225

🇬🇧

Hull, United Kingdom

The Royal Wolverhampton NHS Tr /ID# 127227

🇬🇧

Wolverhampton, United Kingdom

Oxford University Hospitals NHS Foundation Trust The John Radcliffe Hospital /ID# 129324

🇬🇧

Oxford, United Kingdom

Hidaka Clinic of Coloproctology /ID# 125477

🇯🇵

Kurume, Fukuoka, Japan

University of Michigan Hospitals /ID# 122240

🇺🇸

Ann Arbor, Michigan, United States

Charite Universitatsmedizin Berlin Campus Virchow Klinikum /ID# 127203

🇩🇪

Berlin, Germany

Public Institution Kherson City Clinical Hospital named after le.le. Karabelesh /ID# 127233

🇺🇦

Kherson, Ukraine

Ordination Hainburg an der Don /ID# 127185

🇦🇹

Hainburg An Der Donau, Austria

NZOZ All-Medicus /ID# 128740

🇵🇱

Katowice, Slaskie, Poland

Municipal Clinical Hospital #8 /ID# 127235

🇺🇦

Kiev, Ukraine

Szpital Uniwersytecki Nr 2 im. dr J.Biziela w Bydgoszczy /ID# 127141

🇵🇱

Bydgoszcz, Kujawsko-pomorskie, Poland

Centrum Zdrowia MDM /ID# 170303

🇵🇱

Warsaw, Mazowieckie, Poland

Centrum Medyczne LukaMed Joanna Luka /ID# 170302

🇵🇱

Chojnice, Poland

Lviv City Clinical Hospital NO.4 /ID# 127232

🇺🇦

Lviv, Ukraine

CNPE City Hospital No.6 of Zaporizhzhia City Counsil /ID# 127137

🇺🇦

Zaporizhzhia, Ukraine

Norfolk and Norwich Univ Hosp /ID# 127139

🇬🇧

Norwich, Norfolk, United Kingdom

CHU Amiens Picardie /ID# 127194

🇫🇷

Amiens CEDEX 1, Somme, France

Medical Hospital of Tokyo Medical and Dental University /ID# 128315

🇯🇵

Bunkyo-ku, Tokyo, Japan

Vseobecna Nemocnica s poliklinikou Lucenec /ID# 127322

🇸🇰

Lucenec, Slovakia

C.M. Szpital Swietej Rodziny /ID# 127838

🇵🇱

Lodz, Lodzkie, Poland

Gastroenterologicka Ambulancia /ID# 125632

🇸🇰

Bratislava, Slovakia

CHRU Lille - Hôpital Claude Huriez /ID# 127197

🇫🇷

Lille CEDEX, Hauts-de-France, France

Magyar Elhizastudomanyi KKft. /ID# 126589

🇭🇺

Budapest, Hungary

Royal Hampshire County Hosp /ID# 169250

🇬🇧

Winchester, Hampshire, United Kingdom

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