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U-Accomplish: A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Ulcerative Colitis

Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT03653026
Collaborator
(none)
522
Enrollment
379
Locations
2
Arms
25.3
Actual Duration (Months)
1.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this study is to evaluate the efficacy and safety of upadacitinib compared to placebo in inducing clinical remission (per Adapted Mayo score) in participants with moderately to severely active ulcerative colitis (UC).

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Study M14-675 consists of 2 parts, Part 1 and Part 2. Part 1 is a randomized, double-blind, placebo-controlled 8-week induction period. Part 2 is an open-label, 8-week extended treatment period for participants who did not achieve clinical response at Week 8 in Part 1.

Eligible participants are randomized in a 2:1 ratio to one of the two treatment groups (upadacitinib 45 mg or matching placebo) for 8 weeks. The randomization is stratified by biologic inadequate responder (bio-IR) status (bio-IR vs non-bio-IR), corticosteroid use (yes or no), and Adapted Mayo score (≤ 7 or > 7) at Baseline. Within bio-IR, the randomization is further stratified by number of prior biologic treatments (≤ 1 or > 1). Within non-bio-IR, the randomization is further stratified by previous biologic use (yes or no).

Participants who achieve clinical response defined by Adapted Mayo Score at Week 8 or Week 16 and do not meet any study discontinuation criteria are eligible to enroll into Study M14-234 Substudy 3 (NCT02819635; 52-week maintenance study) or Study M14-533 Cohort 1 (NCT03006068; long-term follow-up study).

Study Design

Study Type:
Interventional
Actual Enrollment :
522 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Induction Study to Evaluate the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Moderately to Severely Active Ulcerative Colitis
Actual Study Start Date :
Dec 6, 2018
Actual Primary Completion Date :
Jan 14, 2021
Actual Study Completion Date :
Jan 14, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Upadacitinib 45 mg

Participants received 45 mg upadacitinib once daily (QD) for 8 weeks. Participants who did not achieve clinical response per Adapted Mayo score at Week 8 received upadacitinib 45 mg once daily for 8 additional weeks in the open-label extension period.

Drug: Upadacitinib
Tablet for oral administration
Other Names:
  • ABT-494
  • RINVOQ®

    		•
    Placebo Comparator: Placebo

    Participants received placebo matching to upadacitinib once daily for 8 weeks. Participants who did not achieve clinical response per Adapted Mayo score at Week 8 received upadacitinib 45 mg once daily for 8 weeks in the open-label extension period.

    Drug: Placebo
    Tablet for oral administration

    Drug: Upadacitinib
    Tablet for oral administration
    Other Names:
  • ABT-494
  • RINVOQ®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8 [Week 8]

      The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical remission is defined as an Adapted Mayo score ≤ 2, with SFS ≤ 1 and not higher than Baseline, RBS of 0, and endoscopic subscore ≤ 1.

    Secondary Outcome Measures

    1. Percentage of Participants With Endoscopic Improvement at Week 8 [Week 8]

      Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).

    2. Percentage of Participants With Endoscopic Remission at Week 8 [Week 8]

      Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).

    3. Percentage of Participants Who Achieved Clinical Response Per Adapted Mayo Score at Week 8 [Week 8]

      The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 with higher scores representing more severe disease. Clinical response per the Adapted Mayo Score is defined as a decrease in Adapted Mayo score ≥ 2 points and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.

    4. Percentage of Participants Who Achieved Clinical Response Per Partial Adapted Mayo Score at Week 2 [Week 2]

      The Partial Adapted Mayo Score is a composite score of UC disease activity based on the following 2 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). The overall Partial Adapted Mayo score ranges from 0 to 6 with higher scores representing more severe disease. Clinical response per Partial Adapted Mayo Score is defined as a decrease in Partial Adapted Mayo score ≥ 1 point and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.

    5. Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 8 [Week 8]

      Histologic endoscopic mucosal improvement is defined as an endoscopic subscore of 0 or 1 and a Geboes score ≤ 3.1. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

    6. Percentage of Participants Who Reported No Bowel Urgency at Week 8 [Week 8]

      Bowel urgency was assessed by participants in a subject diary completed once a day.

    7. Percentage of Participants Who Reported No Abdominal Pain at Week 8 [Week 8]

      Abdominal pain was assessed by participants in a subject diary completed once a day.

    8. Percentage of Participants Who Achieved Histologic Improvement at Week 8 [Week 8]

      Histologic improvement is defined as a decrease from Baseline in Geboes score. The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

    9. Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 8 [Baseline (Week 0) to Week 8]

      The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement.

    10. Percentage of Participants Who Achieved Mucosal Healing at Week 8 [Week 8]

      Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

    11. Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 8 [Baseline (Week 0) to Week 8]

      The FACIT fatigue questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. Each question is answered on a 5-point Likert scale: 0 (not at all); 1 (a little bit); 2 (somewhat); 3 (quite a bit); and 4 (very much). The total score ranges from 0 to 52, where higher scores represent less fatigue, and a positive change from Baseline indicates improvement.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Male or female participants ≥ 16 and ≤ 75 years of age at Baseline Note: Adolescent participants at the age of 16 or 17 years old will be eligible to participate if approved by the country or regulatory/health authorities.

    Note: Adolescent participants at the age of 16 or 17 years old must weigh ≥ 40 kilograms and meet the definition of Tanner Stage 5 at the Screening Visit.

    • Diagnosis of Ulcerative Colitis (UC) for 90 days or greater prior to Baseline, confirmed by colonoscopy during the Screening Period, with exclusion of current infection, colonic dysplasia and/or malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of UC, in the assessment of the Investigator, must be available.

    • Active UC with an Adapted Mayo score of 5 to 9 points and endoscopic subscore of 2 to

    • Demonstrated an inadequate response, loss of response, or intolerance to at lease one of the following treatments including, oral aminosalicylates, corticosteroids, immunosuppressants, and/or biologic therapies.

    Note: Participants who have had inadequate response, loss of response to conventional therapy but have not failed biologic therapy (Non-bio-IR) and have received a prior biologic for up to 1 year may be enrolled, however they must have discontinued the biologic for reasons other than inadequate response or intolerance (e.g., change of insurance, well controlled disease), and must meet criteria for inadequate response, loss of response, or intolerance as defined above.

    • Female Participants of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit.

    • If female, participant must meet the contraception recommendation criteria.

    Exclusion Criteria:

    • Participant with current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC).

    • Current diagnosis of fulminant colitis and/or toxic megacolon.

    • Participant with disease limited to the rectum (ulcerative proctitis) during the Screening endoscopy.

    • Received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to Baseline.

    • Participant who received azathioprine or 6-mercaptopurine (6-MP) within 10 days of Baseline.

    • Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period.

    • Participant with previous exposure to Janus Activated Kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib, filgotinib, upadacitinib).

    • Screening laboratory and other analyses show any prespecified abnormal hematologic results.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 East View Medical Research, LLC /ID# 216933 Mobile Alabama United States 36606
    2 CB Flock Research Corporation /ID# 206094 Mobile Alabama United States 36608
    3 Arizona Arthritis & Rheumatology Research, PLLC /ID# 211030 Sun City Arizona United States 85306
    4 Digestive Disease Consultants, A Division of Arizona Digestive Health, P.C /ID# 211887 Tempe Arizona United States 85284-2604
    5 University of Arizona /ID# 208856 Tucson Arizona United States 85724
    6 Citrus Valley Gastroenterology /ID# 205627 Covina California United States 91722-3797
    7 Care Access Research /ID# 217003 Huntington Beach California United States 92648-5994
    8 Moore UC San Diego Cancer Center /ID# 204919 La Jolla California United States 92093
    9 United Medical Doctors /ID# 207867 Los Alamitos California United States 90720-3309
    10 TLC Clinical Research Inc /ID# 216831 Los Angeles California United States 90048
    11 Gastrointestinal Biosciences Clinical Trials, LLC /ID# 205314 Los Angeles California United States 90067-2001
    12 Facey Medical Foundation /ID# 205301 Mission Hills California United States 91345
    13 United Medical Doctors - Murrieta /ID# 205313 Murrieta California United States 92563
    14 InSite Digestive Health Care - Oxnard /ID# 205628 Oxnard California United States 93030
    15 Inland Empire Clinical Trials, LLC /ID# 216164 Rialto California United States 92377
    16 San Diego Clinical Trials /ID# 212122 San Diego California United States 92120
    17 Medical Assoc Research Grp /ID# 205626 San Diego California United States 92123
    18 Delta Waves, Inc. /ID# 206170 Colorado Springs Colorado United States 80918
    19 Western States Clinical Res /ID# 206091 Wheat Ridge Colorado United States 80033-2896
    20 Western Connecticut Medical Group /ID# 208290 Danbury Connecticut United States 06810-6000
    21 Gastroenterology Center of CT /ID# 208291 Hamden Connecticut United States 06518
    22 Gastro Florida /ID# 206174 Clearwater Florida United States 33756
    23 Universal Axon Clinical Research /ID# 213462 Doral Florida United States 33166
    24 Palmetto Research, LLC /ID# 208293 Hialeah Florida United States 33016
    25 Nature Coast Clinical Research - Inverness /ID# 206087 Inverness Florida United States 34452-4717
    26 Encore Borland-Groover Clinical Research /Id# 208128 Jacksonville Florida United States 32256
    27 Cfagi Llc /Id# 207995 Maitland Florida United States 32751-6108
    28 University of Miami /ID# 215445 Miami Florida United States 33136
    29 Coral Research Clinic /ID# 208292 Miami Florida United States 33186-4643
    30 Advanced Research Institute, Inc /ID# 206077 New Port Richey Florida United States 34653
    31 Endoscopic Research, Inc. /ID# 207360 Orlando Florida United States 32803
    32 Omega Research Consultants /ID# 206066 Orlando Florida United States 32810
    33 Clinical Research Trials of Florida, Inc. /ID# 206068 Tampa Florida United States 33607
    34 University of South Florida /ID# 214495 Tampa Florida United States 33612
    35 AdventHealth Tampa /ID# 207363 Tampa Florida United States 33613-4680
    36 Gastroenterology Associates of Central Georgia, LLC /ID# 216940 Macon Georgia United States 31201
    37 Infinite Clinical Trials /ID# 215343 Riverdale Georgia United States 30274
    38 Atlanta Gastroenterology Spec /ID# 206173 Suwanee Georgia United States 30024
    39 Next Innovative Clinical Research - Chicago /ID# 217324 Chicago Illinois United States 60605-2168
    40 The University of Chicago Medical Center /ID# 206172 Chicago Illinois United States 60637-1443
    41 Carle Foundation Hospital /ID# 207397 Effingham Illinois United States 62401
    42 MediSphere Medical Research Center /ID# 206073 Evansville Indiana United States 47714-8011
    43 Indianapolis Gastroenterology /ID# 206381 Indianapolis Indiana United States 46237
    44 University of Iowa Hospitals and Clinics /ID# 206167 Iowa City Iowa United States 52242
    45 Cotton-O'Neil Clinical Res Ctr /ID# 206175 Topeka Kansas United States 66606
    46 Tri-State Gastroenterology /ID# 206124 Crestview Hills Kentucky United States 41017
    47 Houma Digestive Health Special /ID# 206176 Houma Louisiana United States 70360
    48 Louisana Research Center, LLC /ID# 206064 Shreveport Louisiana United States 71105-6800
    49 Gastro Center of Maryland /ID# 206883 Columbia Maryland United States 21045
    50 University of Michigan Health Systems /ID# 206918 Ann Arbor Michigan United States 48109
    51 Huron Gastroenterology Assoc /ID# 205109 Ann Arbor Michigan United States 48197
    52 Clin Res Inst of Michigan, LLC /ID# 207078 Chesterfield Michigan United States 48047
    53 Revival Research Institute, LLC /ID# 207282 Southfield Michigan United States 48034-1659
    54 Center for Digestive Health /ID# 207080 Troy Michigan United States 48098-6363
    55 Mayo Clinic /ID# 205645 Rochester Minnesota United States 55905-0001
    56 University of Mississippi Medical Center /ID# 213116 Jackson Mississippi United States 39216-4500
    57 Southern Therapy and Advanced Research (STAR) LLC /ID# 206069 Jackson Mississippi United States 39216
    58 Las Vegas Medical Research /ID# 206814 Las Vegas Nevada United States 89113
    59 AGA Clinical Research Associates, LLC /ID# 206880 Egg Harbor Township New Jersey United States 08234
    60 Atlantic Digestive Health Inst /ID# 208748 Morristown New Jersey United States 07960
    61 Rutgers Robert Wood Johnson /ID# 207382 New Brunswick New Jersey United States 08901
    62 University of New Mexico Department of Internal Medicine /ID# 214397 Albuquerque New Mexico United States 87131-0001
    63 Advantage Clinical Trials /ID# 206082 Bronx New York United States 10468
    64 NY Scientific /ID# 206080 Brooklyn New York United States 11235
    65 NYU Langone Long Island Clinical Research Associates /ID# 206079 Lake Success New York United States 11042
    66 DiGiovanna Institute for Medical Education & Research /ID# 206885 North Massapequa New York United States 11758
    67 Premier Medical Group - GI Division /ID# 206097 Poughkeepsie New York United States 12601
    68 Gastro Group of Rochester /ID# 206881 Rochester New York United States 14618-5703
    69 Richmond University Medical Center /ID# 213185 Staten Island New York United States 10310-1664
    70 Digestive Health Partners, P.A /ID# 206842 Asheville North Carolina United States 28801
    71 Atrium Health Carolinas Medical Center /ID# 206085 Charlotte North Carolina United States 28203
    72 Charlotte Gastroenterology and Hepatology, PLLC /ID# 206138 Charlotte North Carolina United States 28207
    73 Wake Forest Baptist Medical Center /ID# 206067 Winston-Salem North Carolina United States 27157-0001
    74 Duplicate_Plains Clinical Research Center, LLC /ID# 205111 Fargo North Dakota United States 58104
    75 University of Cincinnati /ID# 205633 Cincinnati Ohio United States 45267-0585
    76 The Ohio State University /ID# 205637 Columbus Ohio United States 43210
    77 Optimed Research, Ltd. /ID# 205638 Columbus Ohio United States 43235
    78 Hometown Urgent Care and Resea /ID# 205630 Dayton Ohio United States 45424
    79 Dayton Gastroenterology, Inc. /ID# 205639 Englewood Ohio United States 45415
    80 Great Lakes Gastroenterology Research LLC /ID# 205631 Mentor Ohio United States 44060-6211
    81 Hightower Clinical /ID# 216336 Oklahoma City Oklahoma United States 73102
    82 Digestive Disease Specialists /ID# 206076 Oklahoma City Oklahoma United States 73112
    83 Options Health Research, LLC /ID# 206707 Tulsa Oklahoma United States 74104
    84 Healthcare Research Consultant /ID# 206706 Tulsa Oklahoma United States 74135
    85 Guthrie Medical Group, PC /ID# 206078 Sayre Pennsylvania United States 18840
    86 Pharmacorp Clinical Trials /ID# 206074 Charleston South Carolina United States 29412
    87 Gastroenterology Associates, P.A. of Greenville /ID# 206098 Greenville South Carolina United States 29615-3593
    88 Gastro One /ID# 206178 Germantown Tennessee United States 38138
    89 East Tennessee Research Institute /ID# 206169 Johnson City Tennessee United States 37604
    90 Quality Medical Research /ID# 206088 Nashville Tennessee United States 37211
    91 Vanderbilt University Medical Center /ID# 210405 Nashville Tennessee United States 37232-0011
    92 TX Clinical Research Institute /ID# 206718 Arlington Texas United States 76012
    93 Inquest Clinical Research /ID# 206132 Baytown Texas United States 77521
    94 Texas Digestive Disease Consultants /ID# 209805 Cedar Park Texas United States 78613-5028
    95 Texas Digestive Disease Consultants /ID# 209948 Cedar Park Texas United States 78613-5028
    96 Baylor Scott & White Center for Inflammatory Bowel Diseases /ID# 207484 Dallas Texas United States 75246
    97 DHAT Research Institute /ID# 206716 Garland Texas United States 75044-2208
    98 Vilo Research Group Inc /ID# 212625 Houston Texas United States 77017-2337
    99 Baylor College of Medicine - Baylor Medical Center /ID# 206717 Houston Texas United States 77030-3411
    100 Centex Studies, Inc. - Houston /ID# 206168 Houston Texas United States 77058
    101 GI Specialists of Houston /ID# 206090 Houston Texas United States 77070-4347
    102 Caprock Gastro Research /ID# 215115 Lubbock Texas United States 79424-3017
    103 Clinical Associates in Research Therapeutics of America, LLC /ID# 206710 San Antonio Texas United States 78212
    104 Southern Star Research Institute, LLC /ID# 205379 San Antonio Texas United States 78229-5390
    105 Baylor Scott & White Center for Diagnostic Medicine /ID# 206096 Temple Texas United States 76508
    106 Duplicate_Tyler Research Institue /ID# 206075 Tyler Texas United States 75701
    107 Gastro Health & Nutrition - Victoria /ID# 205378 Victoria Texas United States 77904
    108 Advanced Research Institute /ID# 206133 Ogden Utah United States 84403
    109 Ctr for Gastrointestinal Healt /ID# 208475 Franklin Virginia United States 23851
    110 Washington Gastroenterology Associates /ID# 206177 Bellevue Washington United States 98004
    111 Virginia Mason - Seattle Orthapedics /ID# 206070 Seattle Washington United States 98101
    112 The Vancouver Clinic, INC. PS /ID# 204973 Vancouver Washington United States 98664
    113 Wisconsin Center for Advanced Research, a division of GI Associates, LLC /ID# 206917 Milwaukee Wisconsin United States 53215
    114 Froedtert Memorial Lutheran Hospital /ID# 206945 Milwaukee Wisconsin United States 53226-3522
    115 Cardio Alem /ID# 211282 San Isidro Buenos Aires Argentina 1642
    116 Mautalen Salud e Investigacion /ID# 206033 Ciudad Autonoma de Buenos Aire Ciuadad Autonoma De Buenos Aires Argentina 1128
    117 Hospital Britanico de Buenos Aires /ID# 209497 Ciudad Autonoma de Buenos Aire Ciuadad Autonoma De Buenos Aires Argentina 1280
    118 Gedyt /ID# 210017 Ciudad Autonoma de Buenos Aire Ciuadad Autonoma De Buenos Aires Argentina 1426
    119 Hospital Privado Univesitario /ID# 206030 Cordoba Argentina 5016
    120 Macquarie University Hospital /ID# 211955 Macquarie University New South Wales Australia 2109
    121 Duplicate_Mater Misericordiae /ID# 212687 South Brisbane Queensland Australia 4101
    122 Griffith University /ID# 211956 Southport Queensland Australia 4222
    123 St Vincent's Hospital Melbourne /ID# 205758 Fitzroy Victoria Australia 3065
    124 Monash Medical Centre /ID# 206486 Melbourne Victoria Australia 3168
    125 Fiona Stanley Hospital /ID# 211642 Murdoch Western Australia Australia 6150
    126 Klinik Landstrasse /ID# 205764 Vienna Wien Austria 1030
    127 Medical University of Vienna /ID# 205763 Vienna Wien Austria 1090
    128 LKH Salzburg and Paracelsus /ID# 208788 Salzburg Austria 5020
    129 Universitair Ziekenhuis Leuven /ID# 205988 Leuven Vlaams-Brabant Belgium 3000
    130 AZ Maria Middelares /ID# 210928 Gent Belgium 9000
    131 University Clinical Centre of the Republic of Srpska /ID# 208053 Banja Luka Republika Srpska Bosnia and Herzegovina 78000
    132 University Clinical Centre of the Republic of Srpska /ID# 208055 Banja Luka Republika Srpska Bosnia and Herzegovina 78000
    133 University Clinical Center Tuzla /ID# 208057 Tuzla Tuzlanski Bosnia and Herzegovina 75000
    134 University Clinical Hospital Mostar /ID# 208054 Mostar Bosnia and Herzegovina 88000
    135 Clinical Center University of Sarajevo /ID# 208058 Sarajevo Bosnia and Herzegovina 71000
    136 Hospital Nossa Senhora das Graças /ID# 206981 Curitiba Parana Brazil 80810-040
    137 Hospital de Clinicas de Porto Alegre /ID# 206985 Porto Alegre Rio Grande Do Sul Brazil 90035-903
    138 Upeclin Fmb - Unesp /Id# 206986 Botucatu Sao Paulo Brazil 18618-686
    139 Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto - USP /ID# 206504 Ribeirão Preto Sao Paulo Brazil 14051-140
    140 Faculdade de Medicina do ABC /ID# 206984 Santo André Sao Paulo Brazil 09060-870
    141 Kaiser Clinica e Hospital Dia /ID# 206982 Sao Jose Do Rio Preto Sao Paulo Brazil 15015-110
    142 University of Calgary - Cumming School of Medicine - Adult Cystic Fibrosis Clini /ID# 205755 Calgary Alberta Canada T2N 4Z6
    143 Allen Whey Khye Lim Professional Corporation /ID# 211167 Edmonton Alberta Canada T5R 1W2
    144 Covenant Health /ID# 205500 Edmonton Alberta Canada T6K 4B2
    145 Percuro Clinical Research, Ltd /ID# 205501 Victoria British Columbia Canada V8V 3M9
    146 Duplicate_Toronto Digestive Disease Asso /ID# 205498 Vaughan Ontario Canada L4L 4Y7
    147 Crchum /Id# 207387 Montreal Quebec Canada H2X 0A9
    148 CIUSSS de l'Estrie - CHUS /ID# 205499 Sherbrooke Quebec Canada J1G 2E8
    149 Research Group /ID# 208037 Santiago Region Metropolitana De Santiago Chile 2540364
    150 M y F Estudios Clínicos Ltda. /ID# 208035 Santiago Region Metropolitana De Santiago Chile 7750495
    151 Hospital Guillermo Grant Benavente de Concepción /ID# 212426 Concepción Chile 4070038
    152 CTR Estudios Clinicos /ID# 208036 Providencia Chile 7500571
    153 Hospital Clinico Universidad De Los Andes /ID# 207426 Santiago Chile 7501504
    154 Sun Yat-sen Memorial Hospital of Sun Yat-sen University /ID# 205267 Guangzhou Guangdong China 510120
    155 The Sixth Affiliated Hosp Sun /ID# 205268 Guangzhou Guangdong China 510655
    156 Affiliated Taihe Hospital of Hubei University of Medicine /ID# 216406 Shiyan Hubei China 442700
    157 Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 205266 Wuhan Hubei China 430022
    158 The First Affiliated Hospital of Nanchang University /ID# 212186 Nanchang Jiangxi China 330006
    159 The First Hospital of Jilin University /ID# 210088 Changchun Jilin China 130021
    160 Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 205333 Shanghai Shanghai China 200025
    161 The second Affiliated hospital of Zhejiang University school of Medicine /ID# 205271 Hangzhou Zhejiang China 310009
    162 West China Hospital, Sichuan University /ID# 205332 Chengdu China 610041
    163 Duplicate_Tianjin Med Univ General Hosp /ID# 205246 Tianjin China 300052
    164 Tongji Hospital Tongji Medical College Huazhong University of Science and Techno /ID# 205265 Wuhan China 430030
    165 Instituto Medico de Alta Tecnologia Oncomédica S.A /ID# 208887 Monteria Cordoba Colombia 230002
    166 Corporacion Hospitalaria Juan Cuidad Sede Denominada Hospital Universitario Mayo /ID# 208886 Bogota DC Cundinamarca Colombia 111221
    167 Hospital Universitario San Vic /ID# 208888 Medellin Colombia 50010
    168 Klinicka bolnica Dubrava Zagreb /ID# 208460 Zagreb Grad Zagreb Croatia 10000
    169 Poliklinika Solmed /ID# 211568 Zagreb Grad Zagreb Croatia 10000
    170 Klinicki bolnicki centar Rijeka /ID# 208650 Rijeka Primorsko-goranska Zupanija Croatia 51000
    171 Klinicki bolnicki centar Split /ID# 217027 Split Croatia 21000
    172 Hepato-Gastroenterologie HK, s.r.o. /ID# 205672 Hradec Kralove Czechia 500 12
    173 CTCenter MaVe s.r.o. /ID# 205671 Olomouc Czechia 779 00
    174 Artroscan s.r.o. /ID# 205668 Ostrava Czechia 722 00
    175 Nemocnice Pardubickeho kraje, a.s. /ID# 213540 Pardubice Czechia 530 03
    176 Nemocnice Milosrdnych sester sv. Karla Boromejskeho v Praze /ID# 216223 Praha Czechia 118 33
    177 Axon Clinical, s.r.o. /ID# 205670 Praha Czechia 140 00
    178 ISCARE a.s. /ID# 209240 Praha Czechia 190 00
    179 East Tallinn Central Hospital /ID# 207564 Tallinn Harjumaa Estonia 10138
    180 West Tallinn Central Hospital /ID# 207356 Tallinn Estonia 10617
    181 North Estonia Medical Centre /ID# 207357 Tallinn Estonia 13419
    182 Tartu University Hospital /ID# 212282 Tartu Estonia 51014
    183 Tampere University Hospital /ID# 206161 Tampere Pirkanmaa Finland 33520
    184 Keski-Suomen Sairaala Nova /ID# 206159 Jyvaskyla Finland 40620
    185 Laakarikeskus Ikioma /ID# 205814 Mikkeli Finland 50100
    186 Tyks /Id# 205813 Turku Finland 20521
    187 Chu de Nice-Hopital L'Archet Ii /Id# 209118 Nice CEDEX 3 Alpes-Maritimes France 06202
    188 Centre Hospitalier Lyon Sud /ID# 209121 Pierre Benite CEDEX Rhone France 69495
    189 Universitatsklinikum Mannheim /ID# 206811 Mannheim Baden-Wuerttemberg Germany 68167
    190 Duplicate_Universitaetsklinikum Tuebingen /ID# 206737 Tübingen Baden-Wuerttemberg Germany 72076
    191 Gastroenterologische Gemeinschaftspraxis Herne /ID# 214576 Herne Nordrhein-Westfalen Germany 44623
    192 Zentrum für Gastroenterologie Saar MVZ GmbH /ID# 215813 Saarbrücken Saarland Germany 66111
    193 Duplicate_Praxis am Bayrischen Platz /ID# 206733 Berlin Germany 10825
    194 Agaplesion Markus Krankenhaus /ID# 206731 Frankfurt am Main Germany 60431
    195 Duplicate_Univ Hosp Schleswig-Holstein /ID# 206791 Kiel Germany 24105
    196 Medizinisches Versorgungszentrum Portal 10 /ID# 207137 Muenster Germany 48155
    197 General Hospital of Athens Laiko /ID# 208671 Athens Attiki Greece 11527
    198 University General Hospital of Heraklion PA.G.N.I /ID# 207061 Heraklion Kriti Greece 711 10
    199 General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 206332 Athens Greece 10676
    200 Duplicate_General Hospital of Thessaloniki Hippokrateio /ID# 208822 Thessaloniki Greece 54642
    201 Bekes Megyei Kozponti Korhaz /ID# 205885 Bekescsaba Hungary 5600
    202 Semmelweis Egyetem /ID# 205883 Budapest Hungary 1085
    203 Soproni Erzsebet Oktato Korhaz es Rehabilitacios Intezet /ID# 207992 Sopron Hungary 9400
    204 Mentahaz Maganorvosi Kozpont /ID# 205882 Szekesfehervar Hungary 8000
    205 Beaumont Hospital /ID# 206509 Dublin Ireland D09 XR63
    206 University Hospital Galway /ID# 218035 Galway Ireland H91 YR71
    207 Rambam Health Care Campus /ID# 206362 Haifa Israel 3109601
    208 Shaare Zedek Medical Center /ID# 206365 Jerusalem Israel 91031
    209 A.O.U. Policlinico S.Orsola-Malpighi /ID# 206351 Bologna Emilia-Romagna Italy 40138
    210 ASST Rhodense/Presidio Ospedaliero di Rho /ID# 216611 Rho Milano Italy 20017
    211 Istituto Clinico Humanitas /ID# 206346 Rozzano Milano Italy 20089
    212 Presidio Columbus-Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Un /ID# 206347 Rome Roma Italy 00168
    213 IRCCS Ospedale Sacro Cuore Don Calabria /ID# 206354 Negrar Verona Italy 37024
    214 Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 206349 Milan Italy 20122
    215 A.O. Ospedali Riuniti Villa Sofia - Cervello /ID# 206350 Palermo Italy 90146
    216 Nagoya City University Hospital /ID# 206058 Nagoya shi Aichi Japan 467-8602
    217 Nagoya University Hospital /ID# 206355 Nagoyashi Aichi Japan 4668560
    218 Toyohashi Municipal Hospital /ID# 207625 Toyohashi-shi Aichi Japan 441-8570
    219 Ieda Hospital /ID# 207479 Toyota-shi Aichi Japan 470-1219
    220 Hirosaki National Hospital /ID# 206387 Hirosaki-shi Aomori Japan 036-8545
    221 Tokatsu Tsujinaka Hospital /ID# 214963 Abiko-shi Chiba Japan 270-1168
    222 Tsujinaka Hospital Kashiwanoha /ID# 209573 Kashiwa-shi Chiba Japan 277-0871
    223 Toho University Medical Center Sakura Hospital /ID# 207705 Sakura-shi Chiba Japan 285-8741
    224 Juntendo University Urayasu Hospital /ID# 208784 Urayasu-shi Chiba Japan 279-0021
    225 Fukui Prefectural Hospital /ID# 210449 Fukui-shi Fukui Japan 910-8526
    226 Fukuoka University Chikushi Hospital /ID# 214405 Chikushino-shi Fukuoka Japan 818-8502
    227 Saiseikai Fukuoka Genaral Hospital /ID# 209482 Fukuoka-shi Fukuoka Japan 810-0001
    228 Kurume University Hospital /ID# 206385 Kurume-shi Fukuoka Japan 830-0011
    229 Ogaki Municipal Hospital /ID# 208227 Ogaki-shi Gifu Japan 503-8502
    230 NHO Fukuyama Medical Center /ID# 206295 Fukuyama-shi Hiroshima Japan 720-8520
    231 Hiroshima University Hospital /ID# 206464 Hiroshima-shi Hiroshima Japan 734-8551
    232 Asahikawa Medical University Hospital /ID# 206404 Midorigaokahiga-shi Hokkaido Japan 078-8510
    233 Obihiro kosei Hospital /ID# 210424 Obihiro-shi Hokkaido Japan 080-0024
    234 Sapporo Tokushukai Hospital /ID# 209448 Sapporo-shi Hokkaido Japan 004-0041
    235 Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital /ID# 206059 Sapporo-shi Hokkaido Japan 060-0033
    236 Sapporo Medical University Hospital /ID# 206314 Sapporo-shi Hokkaido Japan 060-8543
    237 Sapporo Higashi Tokushukai Hospital /ID# 208494 Sapporo-shi Hokkaido Japan 065-0033
    238 Aoyama Clinic /ID# 206452 Kobe-shi Hyogo Japan 650-0015
    239 Hyogo College of Medicine Hospital /ID# 206455 Nishinomiya-shi Hyogo Japan 663-8501
    240 Kanazawa University Hospital /ID# 206316 Kanazawa-shi Ishikawa Japan 920-8641
    241 Iwate Medical University Uchimaru Medical Center /ID# 207051 Morioka-shi Iwate Japan 020-8505
    242 Idzuro Imamura Hospital /ID# 207639 Kagoshima-shi Kagoshima Japan 892-0824
    243 Sameshima Hospital /ID# 207935 Kagoshima-shi Kagoshima Japan 892-0846
    244 St. Marianna University School of Medicine Hospital /ID# 209451 Kawasaki-shi Kanagawa Japan 216-8511
    245 Showa University Fujigaoka Hospital /ID# 208224 Yokohama-shi Kanagawa Japan 227-8501
    246 Kyoto University Hospital /ID# 211809 Kyoto-shi Kyoto Japan 606-8507
    247 Mie University Hospital /ID# 206803 Tsu-shi Mie Japan 514-8507
    248 Yokkaichi Hazu Medical Center /ID# 214348 Yokkaichi-shi Mie Japan 510-0016
    249 National Hospital Organization Sendai Medical Center /ID# 209528 Sendai-shi Miyagi Japan 983-8520
    250 NHO Nagasaki Medical Center /ID# 210822 Omura-shi Nagasaki Japan 856-8562
    251 Kenseikai Dongo Hospital /ID# 208101 Yamatotakada-shi Nara Japan 635-0022
    252 Saiseikai Niigata Hospital /ID# 209921 Niigata-shi Niigata Japan 950-1104
    253 Niigata University Medical & Dental Hospital /ID# 218049 Niigata-shi Niigata Japan 951-8520
    254 Ishida Clinic of IBD and Gastroenterology /ID# 210119 Oita-shi Oita Japan 870-0823
    255 Chikuba Hospital for Proctological and Gastrointestinal Diseases /ID# 206646 Kurashiki-shi Okayama Japan 710-0142
    256 Okayama University Hospital /ID# 217925 Okayama-shi Okayama Japan 700-8558
    257 Kinshukai Infusion Clinic /ID# 207865 Osaka-shi Osaka Japan 530-0011
    258 Kitano Hospital /ID# 210397 Osaka-shi Osaka Japan 530-8480
    259 Japanese Red Cross Osaka Hospital /ID# 209478 Osaka-shi Osaka Japan 543-8555
    260 Osaka City University Hospital /ID# 206457 Osaka-shi Osaka Japan 545-8586
    261 Toyonaka Municipal Hospital /ID# 217082 Toyonaka-shi Osaka Japan 560-0055
    262 Saga University Hospital /ID# 209270 Saga-shi Saga Japan 849-8501
    263 Saitama Medical Center /ID# 206393 Kawagoe-shi Saitama Japan 350-8550
    264 Tokitokai Tokito clinic /ID# 206313 Saitama-shi Saitama Japan 336-0963
    265 National Hospital Organization Higashi-Ohmi General Medical Center /ID# 210710 Higashi-ohmi-shi Shiga Japan 527-8505
    266 Shimane University School of Medicine /ID# 208905 Izumo-shi Shimane Japan 693-0021
    267 Hamamatsu University Hospital /ID# 206459 Hamamatsu-shi Shizuoka Japan 431-3192
    268 NHO Shizuoka Medical Center /ID# 208785 Sunto-gun Shizuoka Japan 411-8611
    269 Tokyo Medical And Dental University, Medical Hospital /ID# 206453 Bunkyo-ku Tokyo Japan 113-8519
    270 St.Luke's International Hospital /ID# 208076 Chuo-ku Tokyo Japan 104-8560
    271 Tokai University Hachioji Hospital /ID# 208903 Hachioji-shi Tokyo Japan 192-0032
    272 Teikyo University Hospital /ID# 209866 Itabashi-ku Tokyo Japan 173-8606
    273 Center Hospital of the National Center for Global Health and Medicine /ID# 209532 Shinjuku-ku Tokyo Japan 162-8655
    274 Tokyo Women's Medical University Hospital /ID# 206460 Shinjuku-ku Tokyo Japan 162-8666
    275 Yamagata University Hospital /ID# 206465 Yamagata-shi Yamagata Japan 990-9585
    276 Tokuyama Central Hospital /ID# 216994 Shunan-shi Yamaguchi Japan 745-8522
    277 Shoyukai Fujita Gastroenterological Hospital /ID# 216493 Takatsuki-shi Japan 569-0086
    278 Kangbuk Samsung Hospital /ID# 206960 Seoul Seoul Teugbyeolsi Korea, Republic of 03181
    279 Dong-A University Hospital /ID# 206955 Busan Korea, Republic of 49201
    280 Pusan National University Hospital /ID# 206956 Busan Korea, Republic of 49241
    281 Yeungnam University Medical Center /ID# 206959 Daegu Korea, Republic of 42415
    282 Duplicate_CHA Bundang Medical Center /ID# 207432 Seongnam-si, Gyeonggi-do Korea, Republic of 13496
    283 Yonsei University Health System, Severance hospital /ID# 206958 Seoul Korea, Republic of 03722
    284 Riga East Clinical Univ Hosp /ID# 206828 Riga Latvia 1038
    285 P. Stradins Clinical Univ Hosp /ID# 206827 Riga Latvia LV-1002
    286 Hospital of Lithuanian University of Health Sciences Kaunas Clinics /ID# 209052 Kaunas Lithuania 50161
    287 Klaipeda Seamens Hospital /ID# 208791 Klaipeda Lithuania 92288
    288 Klaipeda University Hospital /ID# 208790 Klaipeda Lithuania 92288
    289 Vilnius University Hospital /ID# 209051 Vilnius Lithuania LT-08661
    290 Universiti Kebangsaan Malaysia (UKM) Medical Centre /ID# 207662 Kuala Lumpur Selangor Malaysia 56000
    291 Duplicate_Uni Malaya MC /ID# 208936 Kuala Lumpur Malaysia 59100
    292 Morales Vargas Centro de Investigacion S.C. /ID# 211326 Leon Guanajuato Mexico 37000
    293 Clinica de Investigacion en Reumatologia y Obesidad S.C. /ID# 208068 Guadalajara Jalisco Mexico 44650
    294 Centro Regiomontano de Estudios Clínicos ROMA S.C /ID# 208067 Monterrey Nuevo Leon Mexico 64610
    295 Erasmus Medisch Centrum /ID# 205280 Rotterdam Netherlands 3015 GD
    296 Akershus Universitetssykehus_MAIN /ID# 205293 Lorenskog Akershus Norway 1478
    297 Universitetssykehuset Nord-Norge /ID# 205691 Tromsø Troms Norway 9019
    298 Gastromed /Id# 216108 Torun Kujawsko-pomorskie Poland 87-100
    299 Centrum Medyczne Reuma Park w Warszawie /ID# 212913 Warsaw Mazowieckie Poland 02-691
    300 Centrum Zdrowia MDM /ID# 205874 Warszawa Mazowieckie Poland 00-635
    301 NZOZ Vivamed /ID# 216697 Warszawa Mazowieckie Poland 03-580
    302 Instytut Pomnik - Centrum Zdrowia Dziecka /ID# 215070 Warszawa Mazowieckie Poland 04-730
    303 Endoskopia Sp. z o.o. /ID# 212964 Sopot Pomorskie Poland 81-756
    304 Hospital da Senhora da Oliveira Guimaraes, EPE /ID# 205554 Guimaraes Braga Portugal 4835-044
    305 Centro Hospitalar de Entre Douro e Vouga /ID# 205563 Santa Maria Da Feira Porto Portugal 4520-211
    306 Unidade Local de Saúde do Alto Minho, EPE - Hospital Conde de Bertiandos /ID# 205556 Ponte de Lima Viana Do Castelo Portugal 4990-041
    307 Hospital Garcia de Orta, EPE /ID# 206143 Almada Portugal 2805-267
    308 CCA Braga - Hospital de Braga /ID# 206144 Braga Portugal 4710-243
    309 Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital de Santa Maria /ID# 206117 Lisboa Portugal 1649-035
    310 Hospital Santo Antonio dos Cap /ID# 206145 Lisbon Portugal 1150-069
    311 Centro Hospitalar Universitario de Sao Joao, EPE /ID# 206142 Porto Portugal 4200-319
    312 School of Medicine University of Puerto Rico-Medical Science Campus /ID# 209626 San Juan Puerto Rico 00935
    313 Immanuel Kant Baltic Federal University /ID# 208264 Kaliningrad Kaliningradskaya Oblast Russian Federation 236016
    314 NW State Medical Univ na Mechn /ID# 208258 St. Petersburg Leningradskaya Oblast Russian Federation 191015
    315 Perm Clinical Center of the Federal Medical and Biological Agency /ID# 211653 Perm Permskiy Kray Russian Federation 614109
    316 Medical Company Hepatolog /ID# 208261 Samara Samarskaya Oblast Russian Federation 443063
    317 Professor Pasechnikov Gastroenterology and Pankreatology clinic /ID# 211652 Stavropol Stavropol Skiy Kray Russian Federation 355012
    318 Kazan State Medical University /ID# 208256 Kazan Tatarstan, Respublika Russian Federation 420012
    319 Olla-Med Clinic /ID# 215335 Moscow Russian Federation 105554
    320 Republican hospital named after V.A. Baranov /ID# 206507 Petrozavodsk Russian Federation 185019
    321 Euromedservice /ID# 208265 Pushkin Russian Federation 196603
    322 LLC Novaya Clinica /ID# 208260 Pyatigorsk Russian Federation 357532
    323 Clinical Hosp Center Zvezdara /ID# 205258 Belgrade Beograd Serbia 11000
    324 Military Medical Academy /ID# 205257 Belgrade Beograd Serbia 11000
    325 University Clinical Center Serbia /ID# 205256 Belgrade Beograd Serbia 11000
    326 Clin Hosp Ctr Bezanijska Kosa /ID# 206413 Belgrade Beograd Serbia 11080
    327 University Clinical Center of Nis /ID# 206411 NIS Nisavski Okrug Serbia 18000
    328 University Clinical Center Kragujevac /ID# 206410 Kragujevac Sumadijski Okrug Serbia 34000
    329 Clinical Center Vojvodina /ID# 205259 Novi Sad Vojvodina Serbia 21000
    330 General Hospital Leskovac /ID# 217881 Leskovac Serbia 16000
    331 National University Hospital /ID# 209099 Singapore Singapore 119074
    332 Gleneagles Medical Centre /ID# 206954 Singapore Singapore 258499
    333 Tan Tock Seng Hospital /ID# 207663 Singapore Singapore 308433
    334 Medak s.r.o. /ID# 205191 Bratislava Bratislavsky Kraj Slovakia 851 01
    335 Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica /ID# 205147 Banska Bystrica Slovakia 975 17
    336 B+B MED, s.r.o. /ID# 205213 Kosice Slovakia 040 01
    337 Fakultna nemocnica s poliklini /ID# 211372 Nove Zamky Slovakia 940 34
    338 GASTRO I., s.r.o. /ID# 205148 Presov Slovakia 080 01
    339 MD Search /ID# 208084 Boksburg North Gauteng South Africa 1460
    340 Clinresco Centers /ID# 208083 Johannesburg Gauteng South Africa 1619
    341 Lenasia Clinical Trial Centre /ID# 214359 Johannesburg Gauteng South Africa 1820
    342 Wits Clinical Research , Wits Health Consortium (PTY) Ltd /ID# 208082 Johannesburg Gauteng South Africa 2193
    343 Wits Clinical Research Site /ID# 208949 Johannesburg Gauteng South Africa 2193
    344 Mediclinic Milnerton /ID# 207979 CAPE TOWN Milnerton Western Cape South Africa 7441
    345 Kingsbury Hospital /ID# 205281 Cape Town Western Cape South Africa 7708
    346 Private Practice Dr MN Rajabally /ID# 205273 Cape Town Western Cape South Africa 7800
    347 Hospital Clínico Universitario de Santiago-CHUS /ID# 204411 Santiago de Compostela A Coruna Spain 15706
    348 Hospital Unversitario Marques de Valdecilla /ID# 216622 Santander Cantabria Spain 39008
    349 Hospital Universitario Dr. Negrin /ID# 206905 Las Palmas de Gran Canaria Las Palmas Spain 35010
    350 Hospital Universitario A Coruna - CHUAC /ID# 206907 A Coruna Spain 15006
    351 Hospital Clinic de Barcelona /ID# 206906 Barcelona Spain 08036
    352 Hospital Universitario Reina Sofia /ID# 204412 Cordoba Spain 14004
    353 Hospital Universitario Ramon y Cajal /ID# 204410 Madrid Spain 28034
    354 Hospital Universitario La Paz /ID# 214540 Madrid Spain 28046
    355 Hospital Clinico Universitario de Salamanca /ID# 205013 Salamanca Spain 37007
    356 Hospital Universitario y Politecnico La Fe /ID# 206904 Valencia Spain 46026
    357 Kantonsspital St. Gallen /ID# 211310 St. Gallen Sankt Gallen Switzerland 9007
    358 Universitaetsspital Basel /ID# 211381 Basel Switzerland 4031
    359 Inselspital, Universitaetsklinik /ID# 211312 Bern Switzerland 3010
    360 Universitaetsspital Zuerich /ID# 211308 Zurich Switzerland 8091
    361 China Medical University Hosp /ID# 207845 Taichung City Taichung Taiwan 40447
    362 National Taiwan University Hospital /ID# 207847 Taipei City Taipei Taiwan 100
    363 Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 207848 Kaohsiung Taiwan 80708
    364 Taipei Veterans General Hosp /ID# 207849 Taipei City Taiwan 11217
    365 Erciyes University Medical Fac /ID# 207506 Melikgazi Kayseri Turkey 38030
    366 Gazi University Med. Faculty /ID# 208040 Ankara GAZI Turkey 06500
    367 Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty /ID# 207507 Istanbul Turkey 34098
    368 Umraniye Training and Res Hosp /ID# 208206 Istanbul Turkey 34764
    369 Mersin University Medical /ID# 208039 Mersin Turkey 33343
    370 Communal Non-Commercial Enterprize of Kharkiv Regional Council Regional Clinical /ID# 206939 Kharkiv Kharkivska Oblast Ukraine 61204
    371 Kyiv Regional Hospital /ID# 217373 Kyiv Kyivska Oblast Ukraine 04073
    372 PE PMC Acinus, Medical and Diagnostic Center /ID# 217218 Kropyvnytskyi Ukraine 25006
    373 Medical centre of CONSILIUM MEDICAL LLC /ID# 217447 Kyiv Ukraine 04050
    374 Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrogov /ID# 216300 Vinnytsia Ukraine 21018
    375 Basingstoke & North Hampshire /ID# 207985 Basingstoke United Kingdom RG24 9NA
    376 Queen Elizabeth University Hos /ID# 205154 Glasgow United Kingdom G514TF
    377 Huddersfield Royal Infirmary /ID# 217660 Huddersfield United Kingdom HD3 3EA
    378 St. George's Healthcare NHS /ID# 208375 London United Kingdom SW17 0QT
    379 Barts and the London NHS Trust /ID# 205153 Whitechapel United Kingdom E1 1 BB

    Sponsors and Collaborators

    • AbbVie

    Investigators

    • Study Director: ABBVIE INC., AbbVie

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT03653026
    Other Study ID Numbers:
    • M14-675
    • 2016-000642-62
    First Posted:
    Aug 31, 2018
    Last Update Posted:
    Mar 2, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by AbbVie
    Upadacitinib
    ABT-494
    Ulcerative Colitis
    Additional relevant MeSH terms:
    Colitis
    Colitis, Ulcerative
    Ulcer
    Upadacitinib

    Study Results

    Participant Flow

    Recruitment Details This study included a Screening Period of up to 5 weeks, Part 1, and Part 2. Part 1 was a randomized, double-blind, placebo-controlled 8-week induction period. Part 2 was an open-label, 8-week extended treatment period for participants who were clinical non-responders in Part 1. Participants with moderately to severely active ulcerative colitis (UC) were randomized at 204 sites in 41 countries.
    Pre-assignment Detail In Part 1 participants were randomized in a 2:1 ratio to upadacitinib or placebo. Randomization was stratified by biologic-inadequate responder (Bio-IR) status (bio-IR vs non-bio-IR), corticosteroid use (yes or no), and Adapted Mayo score (≤ 7 or > 7) at Baseline. Within bio-IR, randomization was further stratified by number of prior biologic treatments (≤ 1 or > 1). Within non-bio-IR, randomization was further stratified by previous biologic use (yes or no).
    Arm/Group Title Part 1: Upadacitinib 45 mg Part 1: Placebo Part 2: Upadacitinib 45 mg / Upadacitinib 45 mg Part 2: Placebo / Upadacitinib 45 mg
    Arm/Group Description Participants received 45 mg upadacitinib once daily (QD) for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks. Participants initially assigned to upadacitinib who did not achieve clinical response per Adapted Mayo score at Week 8 in Part 1 received upadacitinib 45 mg once daily for 8 additional weeks in the open-label extension period. Participants initially assigned to placebo who did not achieve clinical response per Adapted Mayo score at Week 8 in Part 1 received upadacitinib 45 mg once daily for 8 weeks in the open-label extension period.
    Period Title: Part 1: Placebo-controlled Period
    STARTED 345 177 0 0
    Received Treatment 344 177 0 0
    COMPLETED 334 164 0 0
    NOT COMPLETED 11 13 0 0
    Period Title: Part 1: Placebo-controlled Period
    STARTED 0 0 68 116
    COMPLETED 0 0 65 111
    NOT COMPLETED 0 0 3 5

    Baseline Characteristics

    Arm/Group Title Upadacitinib 45 mg Placebo Total
    Arm/Group Description Participants received 45 mg upadacitinib once daily (QD) for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks. Total of all reporting groups
    Overall Participants 345 177 522
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    42.2
    (14.73)
    42.2
    (14.44)
    42.2
    (14.62)
    Age, Customized (Count of Participants)
    < 18 years
    6
    1.7%
    3
    1.7%
    9
    1.7%
    ≥ 18 years to < 40 years
    160
    46.4%
    81
    45.8%
    241
    46.2%
    ≥ 40 years to < 65 years
    146
    42.3%
    79
    44.6%
    225
    43.1%
    ≥ 65 years
    33
    9.6%
    14
    7.9%
    47
    9%
    Sex: Female, Male (Count of Participants)
    Female
    129
    37.4%
    67
    37.9%
    196
    37.5%
    Male
    216
    62.6%
    110
    62.1%
    326
    62.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    26
    7.5%
    16
    9%
    42
    8%
    Not Hispanic or Latino
    319
    92.5%
    161
    91%
    480
    92%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    White
    238
    69%
    127
    71.8%
    365
    69.9%
    Black or African American
    11
    3.2%
    6
    3.4%
    17
    3.3%
    Asian
    94
    27.2%
    41
    23.2%
    135
    25.9%
    American Indian or Alaska Native
    0
    0%
    1
    0.6%
    1
    0.2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    0.6%
    1
    0.2%
    Multiple
    2
    0.6%
    1
    0.6%
    3
    0.6%
    Biologic-inadequate Responder (Bio-IR) Status (Count of Participants)
    Bio-IR
    175
    50.7%
    91
    51.4%
    266
    51%
    Non-Bio-IR
    170
    49.3%
    86
    48.6%
    256
    49%
    Baseline Corticosteroid Use (Count of Participants)
    Yes
    123
    35.7%
    75
    42.4%
    198
    37.9%
    No
    222
    64.3%
    102
    57.6%
    324
    62.1%
    Adapted Mayo Score Strata (Count of Participants)
    ≤ 7
    205
    59.4%
    104
    58.8%
    309
    59.2%
    > 7
    138
    40%
    73
    41.2%
    211
    40.4%
    Missing
    2
    0.6%
    0
    0%
    2
    0.4%
    Bio-IR: Number of Prior Biologic Treatments (Count of Participants)
    ≤ 1 prior biologic
    58
    16.8%
    33
    18.6%
    91
    17.4%
    > 1 prior biologic
    117
    33.9%
    58
    32.8%
    175
    33.5%
    Non-Bio-IR: Prior Exposure to Biologic Therapy (Count of Participants)
    Yes
    1
    0.3%
    5
    2.8%
    6
    1.1%
    No
    169
    49%
    81
    45.8%
    250
    47.9%
    Disease Duration (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    7.273
    (6.4459)
    7.584
    (7.6701)
    7.379
    (6.8804)
    Adapted Mayo Score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    7.00
    (1.216)
    7.05
    (1.236)
    7.02
    (1.222)
    Average Stool Frequency Subscore (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    2.55
    (0.626)
    2.64
    (0.551)
    2.58
    (0.603)
    Average Rectal Bleeding Subscore (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    1.77
    (0.966)
    1.71
    (1.049)
    1.75
    (0.995)
    Average Endoscopy Subscore (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    2.7
    (0.47)
    2.7
    (0.46)
    2.7
    (0.46)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8
    Description The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical remission is defined as an Adapted Mayo score ≤ 2, with SFS ≤ 1 and not higher than Baseline, RBS of 0, and endoscopic subscore ≤ 1.
    Time Frame Week 8

    Outcome Measure Data

    Analysis Population Description
    The Part 1 intent-to-treat population (ITT1) includes randomized participants who received at least 1 dose of study drug in Part 1. The ITT1 population excludes 6 participants from 1 site with non-compliance. Non-responder imputation incorporating multiple imputation to handle missing data due to Coronavirus Disease - 2019 (COVID-19) was used.
    Arm/Group Title Upadacitinib 45 mg Placebo
    Arm/Group Description Participants received 45 mg upadacitinib once daily for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks.
    Measure Participants 341 174
    Number (95% Confidence Interval) [percentage of participants]
    33.5
    9.7%
    4.1
    2.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
    Method Cochran-Mantel-Haenszel
    Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
    Method of Estimation Estimation Parameter Adjusted Response Rate Difference
    Estimated Value 29.0
    Confidence Interval (2-Sided) 95%
    23.2 to 34.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference = Upadacitinib 45 mg - Placebo
    2. Secondary Outcome
    Title Percentage of Participants With Endoscopic Improvement at Week 8
    Description Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
    Time Frame Week 8

    Outcome Measure Data

    Analysis Population Description
    ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
    Arm/Group Title Upadacitinib 45 mg Placebo
    Arm/Group Description Participants received 45 mg upadacitinib once daily for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks.
    Measure Participants 341 174
    Number (95% Confidence Interval) [percentage of participants]
    44.0
    12.8%
    8.3
    4.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
    Method Cochran-Mantel-Haenszel
    Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
    Method of Estimation Estimation Parameter Adjusted Response Rate Difference
    Estimated Value 35.1
    Confidence Interval (2-Sided) 95%
    28.6 to 41.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference = Upadacitinib 45 mg - Placebo
    3. Secondary Outcome
    Title Percentage of Participants With Endoscopic Remission at Week 8
    Description Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
    Time Frame Week 8

    Outcome Measure Data

    Analysis Population Description
    ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
    Arm/Group Title Upadacitinib 45 mg Placebo
    Arm/Group Description Participants received 45 mg upadacitinib once daily for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks.
    Measure Participants 341 174
    Number (95% Confidence Interval) [percentage of participants]
    18.2
    5.3%
    1.7
    1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
    Method Cochran-Mantel-Haenszel
    Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
    Method of Estimation Estimation Parameter Adjusted Response Rate Difference
    Estimated Value 15.9
    Confidence Interval (2-Sided) 95%
    11.4 to 20.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference = Upadacitinib 45 mg - Placebo
    4. Secondary Outcome
    Title Percentage of Participants Who Achieved Clinical Response Per Adapted Mayo Score at Week 8
    Description The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 with higher scores representing more severe disease. Clinical response per the Adapted Mayo Score is defined as a decrease in Adapted Mayo score ≥ 2 points and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.
    Time Frame Week 8

    Outcome Measure Data

    Analysis Population Description
    ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
    Arm/Group Title Upadacitinib 45 mg Placebo
    Arm/Group Description Participants received 45 mg upadacitinib once daily for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks.
    Measure Participants 341 174
    Number (95% Confidence Interval) [percentage of participants]
    74.5
    21.6%
    25.4
    14.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
    Method Cochran-Mantel-Haenszel
    Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
    Method of Estimation Estimation Parameter Adjusted Response Rate Difference
    Estimated Value 49.4
    Confidence Interval (2-Sided) 95%
    41.7 to 57.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference = Upadacitinib 45 mg - Placebo
    5. Secondary Outcome
    Title Percentage of Participants Who Achieved Clinical Response Per Partial Adapted Mayo Score at Week 2
    Description The Partial Adapted Mayo Score is a composite score of UC disease activity based on the following 2 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). The overall Partial Adapted Mayo score ranges from 0 to 6 with higher scores representing more severe disease. Clinical response per Partial Adapted Mayo Score is defined as a decrease in Partial Adapted Mayo score ≥ 1 point and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.
    Time Frame Week 2

    Outcome Measure Data

    Analysis Population Description
    ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
    Arm/Group Title Upadacitinib 45 mg Placebo
    Arm/Group Description Participants received 45 mg upadacitinib once daily for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks.
    Measure Participants 341 174
    Number (95% Confidence Interval) [percentage of participants]
    63.3
    18.3%
    25.9
    14.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
    Method Cochran-Mantel-Haenszel
    Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
    Method of Estimation Estimation Parameter Adjusted Response Rate Difference
    Estimated Value 37.0
    Confidence Interval (2-Sided) 95%
    28.8 to 45.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference = Upadacitinib 45 mg - Placebo
    6. Secondary Outcome
    Title Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 8
    Description Histologic endoscopic mucosal improvement is defined as an endoscopic subscore of 0 or 1 and a Geboes score ≤ 3.1. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.
    Time Frame Week 8

    Outcome Measure Data

    Analysis Population Description
    ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
    Arm/Group Title Upadacitinib 45 mg Placebo
    Arm/Group Description Participants received 45 mg upadacitinib once daily for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks.
    Measure Participants 341 174
    Number (95% Confidence Interval) [percentage of participants]
    36.7
    10.6%
    5.9
    3.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
    Method Cochran-Mantel-Haenszel
    Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
    Method of Estimation Estimation Parameter Adjusted Response Rate Difference
    Estimated Value 30.1
    Confidence Interval (2-Sided) 95%
    24.1 to 36.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference = Upadacitinib 45 mg - placebo
    7. Secondary Outcome
    Title Percentage of Participants Who Reported No Bowel Urgency at Week 8
    Description Bowel urgency was assessed by participants in a subject diary completed once a day.
    Time Frame Week 8

    Outcome Measure Data

    Analysis Population Description
    ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
    Arm/Group Title Upadacitinib 45 mg Placebo
    Arm/Group Description Participants received 45 mg upadacitinib once daily for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks.
    Measure Participants 341 174
    Number (95% Confidence Interval) [percentage of participants]
    53.7
    15.6%
    25.9
    14.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
    Method Cochran-Mantel-Haenszel
    Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (<= 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
    Method of Estimation Estimation Parameter Adjusted Response Rate Difference
    Estimated Value 27.1
    Confidence Interval (2-Sided) 95%
    19.0 to 35.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference = Upadacitinib 45 mg - Placebo
    8. Secondary Outcome
    Title Percentage of Participants Who Reported No Abdominal Pain at Week 8
    Description Abdominal pain was assessed by participants in a subject diary completed once a day.
    Time Frame Week 8

    Outcome Measure Data

    Analysis Population Description
    ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
    Arm/Group Title Upadacitinib 45 mg Placebo
    Arm/Group Description Participants received 45 mg upadacitinib once daily for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks.
    Measure Participants 341 174
    Number (95% Confidence Interval) [percentage of participants]
    53.7
    15.6%
    24.1
    13.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
    Method Cochran-Mantel-Haenszel
    Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
    Method of Estimation Estimation Parameter Adjusted Response Rate Difference
    Estimated Value 29.1
    Confidence Interval (2-Sided) 95%
    20.9 to 37.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference = Upadacitinib 45 mg - Placebo
    9. Secondary Outcome
    Title Percentage of Participants Who Achieved Histologic Improvement at Week 8
    Description Histologic improvement is defined as a decrease from Baseline in Geboes score. The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.
    Time Frame Week 8

    Outcome Measure Data

    Analysis Population Description
    ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
    Arm/Group Title Upadacitinib 45 mg Placebo
    Arm/Group Description Participants received 45 mg upadacitinib once daily for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks.
    Measure Participants 341 174
    Number (90% Confidence Interval) [percentage of participants]
    62.2
    18%
    24.5
    13.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
    Method Cochran-Mantel-Haenszel
    Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
    Method of Estimation Estimation Parameter Adjusted Response Rate Difference
    Estimated Value 37.9
    Confidence Interval (2-Sided) 95%
    29.8 to 46.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference = Upadacitinib 45 mg - Placebo
    10. Secondary Outcome
    Title Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 8
    Description The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement.
    Time Frame Baseline (Week 0) to Week 8

    Outcome Measure Data

    Analysis Population Description
    ITT1 population with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases up to Week 8 was used except for measurements at or after the occurrence of UC-related corticosteroids intercurrent event were excluded.
    Arm/Group Title Upadacitinib 45 mg Placebo
    Arm/Group Description Participants received 45 mg upadacitinib once daily for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks.
    Measure Participants 315 156
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    52.2
    21.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
    Method Mixed-effect model repeated measurement
    Comments MMRM with Baseline, treatment, visit, treatment-by-visit interaction, and strata (Baseline Adapted Mayo score, corticosteroid use, and bio-IR status).
    Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
    Estimated Value 31.2
    Confidence Interval (2-Sided) 95%
    24.98 to 37.36
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.15
    Estimation Comments Difference = Upadacitinib 45 mg - Placebo
    11. Secondary Outcome
    Title Percentage of Participants Who Achieved Mucosal Healing at Week 8
    Description Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.
    Time Frame Week 8

    Outcome Measure Data

    Analysis Population Description
    ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
    Arm/Group Title Upadacitinib 45 mg Placebo
    Arm/Group Description Participants received 45 mg upadacitinib once daily for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks.
    Measure Participants 341 174
    Number (95% Confidence Interval) [percentage of participants]
    13.5
    3.9%
    1.7
    1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
    Method Cochran-Mantel-Haenszel
    Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
    Method of Estimation Estimation Parameter Adjusted Response Rate Difference
    Estimated Value 11.3
    Confidence Interval (2-Sided) 95%
    7.2 to 15.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference = Upadacitinib 45 mg - Placebo
    12. Secondary Outcome
    Title Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 8
    Description The FACIT fatigue questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. Each question is answered on a 5-point Likert scale: 0 (not at all); 1 (a little bit); 2 (somewhat); 3 (quite a bit); and 4 (very much). The total score ranges from 0 to 52, where higher scores represent less fatigue, and a positive change from Baseline indicates improvement.
    Time Frame Baseline (Week 0) to Week 8

    Outcome Measure Data

    Analysis Population Description
    ITT1 population with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases up to Week 8 was used except for measurements at or after the occurrence of UC-related corticosteroids intercurrent event were excluded.
    Arm/Group Title Upadacitinib 45 mg Placebo
    Arm/Group Description Participants received 45 mg upadacitinib once daily for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks.
    Measure Participants 312 155
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    9.4
    3.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
    Method Mixed-effect model repeated measurement
    Comments MMRM with Baseline, treatment, visit, treatment-by-visit interaction, and strata (Baseline Adapted Mayo score, corticosteroid use, and bio-IR status).
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 6.0
    Confidence Interval (2-Sided) 95%
    4.19 to 7.73
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.9
    Estimation Comments Difference = Upadacitinib 45 mg - Placebo

    Adverse Events

    Time Frame Part 1: From first dose of study drug up to 30 days after the last dose (up to 12 weeks) or until first dose of study drug in Part 2 or first dose of study drug in M14-234 (NCT02819635; maintenance study) or M14-533 (NCT03006068; long term extension). Part 2: From the first dose of study drug in Part 2 up to 30 days after last dose (up to 12 weeks) or until first dose of study drug in M14-234 (maintenance study) or the first dose date of study drug in M14-533 (long-term extension study).
    Adverse Event Reporting Description
    Arm/Group Title Part 1: Upadacitinib 45 mg Part 1: Placebo Part 2: Upadacitinib 45 mg / Upadacitinib 45 mg Part 2: Placebo / Upadacitinib 45 mg
    Arm/Group Description Participants received 45 mg upadacitinib once daily (QD) for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks. Participants initially assigned to upadacitinib who did not achieve clinical response per Adapted Mayo score at Week 8 in Part 1 received upadacitinib 45 mg once daily for 8 additional weeks in the open-label extension period. Participants initially assigned to placebo who did not achieve clinical response per Adapted Mayo score at Week 8 in Part 1 received upadacitinib 45 mg once daily for 8 weeks in the open-label extension period.
    All Cause Mortality
    Part 1: Upadacitinib 45 mg Part 1: Placebo Part 2: Upadacitinib 45 mg / Upadacitinib 45 mg Part 2: Placebo / Upadacitinib 45 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/344 (0%) 0/177 (0%) 0/68 (0%) 0/116 (0%)
    Serious Adverse Events
    Part 1: Upadacitinib 45 mg Part 1: Placebo Part 2: Upadacitinib 45 mg / Upadacitinib 45 mg Part 2: Placebo / Upadacitinib 45 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/344 (3.2%) 8/177 (4.5%) 1/68 (1.5%) 4/116 (3.4%)
    Blood and lymphatic system disorders
    ANAEMIA 1/344 (0.3%) 1 1/177 (0.6%) 1 0/68 (0%) 0 0/116 (0%) 0
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT 0/344 (0%) 0 0/177 (0%) 0 0/68 (0%) 0 1/116 (0.9%) 1
    ABDOMINAL PAIN LOWER 0/344 (0%) 0 0/177 (0%) 0 0/68 (0%) 0 1/116 (0.9%) 1
    COLITIS 0/344 (0%) 0 1/177 (0.6%) 1 0/68 (0%) 0 0/116 (0%) 0
    COLITIS ULCERATIVE 4/344 (1.2%) 4 3/177 (1.7%) 3 1/68 (1.5%) 1 1/116 (0.9%) 1
    LARGE INTESTINE PERFORATION 0/344 (0%) 0 1/177 (0.6%) 1 0/68 (0%) 0 0/116 (0%) 0
    General disorders
    CHEST PAIN 1/344 (0.3%) 1 0/177 (0%) 0 0/68 (0%) 0 0/116 (0%) 0
    Infections and infestations
    COVID-19 PNEUMONIA 1/344 (0.3%) 1 0/177 (0%) 0 0/68 (0%) 0 1/116 (0.9%) 1
    DENGUE FEVER 1/344 (0.3%) 1 0/177 (0%) 0 0/68 (0%) 0 0/116 (0%) 0
    ENTEROCOCCAL INFECTION 0/344 (0%) 0 1/177 (0.6%) 1 0/68 (0%) 0 0/116 (0%) 0
    ESCHERICHIA INFECTION 0/344 (0%) 0 1/177 (0.6%) 1 0/68 (0%) 0 0/116 (0%) 0
    Injury, poisoning and procedural complications
    GASTROINTESTINAL STOMA NECROSIS 0/344 (0%) 0 1/177 (0.6%) 1 0/68 (0%) 0 0/116 (0%) 0
    HAND FRACTURE 1/344 (0.3%) 1 0/177 (0%) 0 0/68 (0%) 0 0/116 (0%) 0
    Metabolism and nutrition disorders
    MALNUTRITION 1/344 (0.3%) 1 0/177 (0%) 0 0/68 (0%) 0 0/116 (0%) 0
    Psychiatric disorders
    ACUTE PSYCHOSIS 1/344 (0.3%) 1 0/177 (0%) 0 0/68 (0%) 0 0/116 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE 0/344 (0%) 0 0/177 (0%) 0 0/68 (0%) 0 1/116 (0.9%) 1
    PULMONARY EMBOLISM 0/344 (0%) 0 1/177 (0.6%) 1 0/68 (0%) 0 0/116 (0%) 0
    Skin and subcutaneous tissue disorders
    PYODERMA GANGRENOSUM 0/344 (0%) 0 1/177 (0.6%) 1 0/68 (0%) 0 0/116 (0%) 0
    Vascular disorders
    PELVIC VENOUS THROMBOSIS 0/344 (0%) 0 1/177 (0.6%) 1 0/68 (0%) 0 0/116 (0%) 0
    Other (Not Including Serious) Adverse Events
    Part 1: Upadacitinib 45 mg Part 1: Placebo Part 2: Upadacitinib 45 mg / Upadacitinib 45 mg Part 2: Placebo / Upadacitinib 45 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 32/344 (9.3%) 11/177 (6.2%) 10/68 (14.7%) 17/116 (14.7%)
    Blood and lymphatic system disorders
    ANAEMIA 0/344 (0%) 0 0/177 (0%) 0 4/68 (5.9%) 4 3/116 (2.6%) 3
    General disorders
    PYREXIA 0/344 (0%) 0 0/177 (0%) 0 4/68 (5.9%) 4 4/116 (3.4%) 4
    Investigations
    BLOOD CREATINE PHOSPHOKINASE INCREASED 0/344 (0%) 0 0/177 (0%) 0 4/68 (5.9%) 4 5/116 (4.3%) 5
    Nervous system disorders
    HEADACHE 8/344 (2.3%) 9 9/177 (5.1%) 10 0/68 (0%) 0 0/116 (0%) 0
    Skin and subcutaneous tissue disorders
    ACNE 24/344 (7%) 25 3/177 (1.7%) 3 0/68 (0%) 0 6/116 (5.2%) 6

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection

    Results Point of Contact

    Name/Title Global Medical Services
    Organization AbbVie
    Phone 800-633-9110
    Email abbvieclinicaltrials@abbvie.com
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT03653026
    Other Study ID Numbers:
    • M14-675
    • 2016-000642-62
    First Posted:
    Aug 31, 2018
    Last Update Posted:
    Mar 2, 2022
    Last Verified:
    Feb 1, 2022