Efficacy and Safety of Adalimumab in Subjects With Moderately to Severely Active Ulcerative Colitis

A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction and Maintenance of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis

This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of the human anti-tumor necrosis factor (TNF) monoclonal antibody adalimumab (ADA) in patients with moderately to severely active ulcerative colitis (UC).

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Biological: adalimumab; Biological: placebo

Detailed Description

This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of adalimumab (ADA) in patients with moderately to severely active ulcerative colitis (UC).

The duration of the study was up to 65 weeks, including a Screening Period of up to 3 weeks, a double-blind (DB) placebo-controlled treatment period of up to 52 weeks, and a 70 day follow-up phone call for participants who prematurely discontinued or who did not enroll in the extension study NCT# 00573794 (M10-223).

Adult participants with moderate to severe UC (Mayo score of 6 to 12 points with endoscopy subscore of 2 to 3 points), confirmed by colonoscopy with biopsy or flexible sigmoidoscopy with biopsy, were to be enrolled at approximately 120 sites worldwide. Planned enrollment was 500 participants.

Participants were to be stratified by prior exposure to infliximab and/or other anti-TNF agents, and randomized in a 1:1 ratio to receive ADA or placebo by subcutaneous injection. Participants assigned to the ADA treatment arm were to receive an induction dose of 160 mg at Week 0 and 80 mg at Week 2, and 40 mg every other week (eow) starting at Week 4. Participants assigned to the placebo treatment arm were to receive matching placebo during the same period of time. At or after Week 10, participants who met the criteria for inadequate response could be switched to open-label (OL) ADA 40 mg eow beginning at Week 12. Inadequate response was defined as:

• Partial Mayo score greater than or equal to Baseline score on 2 consecutive visits at least 14 days apart (for participants with a partial Mayo score of 4 to 7 at Baseline).
• Partial Mayo score greater than or equal to 7 on 2 consecutive visits at least 14 days apart (for participants with a partial Mayo score of 8 or 9 at Baseline).

Participants who demonstrated inadequate response at 2 consecutive visits at least 14 days apart while on OL administration ADA 40 mg eow were permitted to dose escalate to ADA 40 mg weekly (ew). Participants with persistent inadequate response while on ADA 40 mg ew may have been discontinued from the study at the Investigator's discretion. Upon completion of the study, participants had the option to enroll into the OL extension Study M10-223 in which they could receive ADA treatment.

Efficacy and safety measurements were performed throughout the study. A follow-up phone call was made 70 days after the last dose of study drug to obtain information on any ongoing or new adverse events (AEs) for all participants who terminated early or who did not enroll in the OL extension study.

• Study Type: Interventional
• Enrollment (Actual): 518
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1181ACH
    • Site Ref # / Investigator 6853
• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Site Ref # / Investigator 13722
  • New South Wales
    • Bankstown, New South Wales, Australia, NSW 2200
      • Site Ref # / Investigator 16141
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Site Ref # / Investigator 13723
  • South Australia
    • Bedford Park, South Australia, Australia, SA 5042
      • Site Ref # / Investigator 10706
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Site Ref # / Investigator 14882
    • Malvern, Victoria, Australia, 3144
      • Site Ref # / Investigator 9002
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Site Ref # / Investigator 10704
• Austria
  • Vienna, Austria, 1090
    • Site Ref # / Investigator 9802
• Belgium
  • Bonheiden, Belgium, 2820
    • Site Ref # / Investigator 5256
  • Brussels, Belgium, 1070
    • Site Ref # / Investigator 5253
  • Brussels, Belgium, 1200
    • Site Ref # / Investigator 6225
  • Ghent, Belgium, 9000
    • Site Ref # / Investigator 6079
  • Leuven, Belgium, 3000
    • Site Ref # / Investigator 6078
• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, B1Y 1Z9
      • Site Ref # / Investigator 10423
    • Victoria, British Columbia, Canada, V8T 5G4
      • Site Ref # / Investigator 3766
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Site Ref # / Investigator 3769
    • Sudbury, Ontario, Canada, P3E 2N8
      • Site Ref # / Investigator 13556
    • Toronto, Ontario, Canada, M5G 1X5
      • Site Ref # / Investigator 3736
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Site Ref # / Investigator 3771
    • Montreal, Quebec, Canada, H3G 1A4
      • Site Ref # / Investigator 3764
    • Montreal, Quebec, Canada, H3T 1E2
      • Site Ref # / Investigator 3768
    • Quebec City, Quebec, Canada, G1S 4L8
      • Site Ref # / Investigator 3770
• Czech Republic
  • Ceske Budejovice, Czech Republic, 370 87
    • Site Ref # / Investigator 7021
  • Hradec Kravlove 12, Czech Republic, 500 12
    • Site Ref # / Investigator 6307
  • Olomouc, Czech Republic, 775 20
    • Site Ref # / Investigator 6606
  • Prague 4, Czech Republic, 140 21
    • Site Ref # / Investigator 7481
  • Prague 5, Czech Republic, 15006
    • Site Ref # / Investigator 7479
• Denmark
  • Hvidovre, Denmark, DK-2650
    • Site Ref # / Investigator 6483
  • Odense C, Denmark, 5000
    • Site Ref # / Investigator 7477
• France
  • Clichy, France, 92110
    • Site Ref # / Investigator 6231
  • Lille Cedex, France, 59037
    • Site Ref # / Investigator 7476
  • Pessac Cedex, France, 33600
    • Site Ref # / Investigator 7475
  • Toulouse, France, 31059
    • Site Ref # / Investigator 7474
• Germany
  • Hamburg, Germany, 20148
    • Site Ref # / Investigator 15321
  • Hamburg, Germany, 22559
    • Site Ref # / Investigator 9069
  • Magdeburg, Germany, 39120
    • Site Ref # / Investigator 14642
  • Minden, Germany, 32423
    • Site Ref # / Investigator 9067
  • Muenster, Germany, 48159
    • Site Ref # / Investigator 14761
  • Munich, Germany, 80639
    • Site Ref # / Investigator 14661
  • Munich, Germany, 81377
    • Site Ref # / Investigator 9801
  • Regensburg, Germany, 93053
    • Site Ref # / Investigator 5247
• Hungary
  • Budapest, Hungary, H-1076
    • Site Ref # / Investigator 7485
  • Budapest, Hungary, H-1135
    • Site Ref # / Investigator 5025
  • Debrecen, Hungary, 4032
    • Site Ref # / Investigator 10625
  • Gyula, Hungary, 5700
    • Site Ref # / Investigator 14104
  • Miskoic, Hungary, H-3051
    • Site Ref # / Investigator 4987
  • Miskolc, Hungary, H-3526
    • Site Ref # / Investigator 5036
• Israel
  • Kfar Saba, Israel, 44281
    • Site Ref # / Investigator 12744
  • Petah Tikva, Israel, 49100
    • Site Ref # / Investigator 10623
  • Tel Aviv, Israel, 64239
    • Site Ref # / Investigator 15361
• New Zealand
  • Auckland, New Zealand, 0620
    • Site Ref # / Investigator 13301
  • Auckland, New Zealand, 1148
    • Site Ref # / Investigator 13181
  • Christchurch, New Zealand, 8011
    • Site Ref # / Investigator 13148
  • Hamilton, New Zealand
    • Site Ref # / Investigator 13482
• Norway
  • Gjovik, Norway, 2819
    • Site Ref # / Investigator 9561
  • Oslo, Norway, 0027
    • Site Ref # / Investigator 5197
  • Oslo, Norway, 0514
    • Site Ref # / Investigator 6297
  • Tromso, Norway, 9038
    • Site Ref # / Investigator 5194
  • Trondheim, Norway, 7006
    • Site Ref # / Investigator 5193
• Poland
  • Lodz, Poland, 90-153
    • Site Ref # / Investigator 5242
  • Warsaw, Poland, 02 781
    • Site Ref # / Investigator 5266
  • Warsaw, Poland, 02-507
    • Site Ref # / Investigator 5265
  • Wroclaw, Poland, 54-144
    • Site Ref # / Investigator 15263
• Portugal
  • Faro, Portugal, 8000-386
    • Site Ref # / Investigator 5264
  • Lisbon, Portugal, 1150-314
    • Site Ref # / Investigator 7473
  • Lisbon, Portugal, 1769-001
    • Site Ref # / Investigator 5263
• Spain
  • Barcelona, Spain, 08036
    • Site Ref # / Investigator 5211
  • Madrid, Spain, 28040
    • Site Ref # / Investigator 5212
• Switzerland
  • Basel, Switzerland, 4031
    • Site Ref # / Investigator 10221
  • Bern, Switzerland, 3010
    • Site Ref # / Investigator 10222
  • Zurich, Switzerland, 8091
    • Site Ref # / Investigator 9162
• United States
  • California
    • Anaheim, California, United States, 92801
      • Site Ref # / Investigator 5394
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033
      • Site Ref # / Investigator 3753
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Site Ref # / Investigator 3754
  • Florida
    • Gainesville, Florida, United States, 32607
      • Site Ref # / Investigator 12903
    • Hollywood, Florida, United States, 33021
      • Site Ref # / Investigator 3747
    • Jacksonville, Florida, United States, 32256
      • Site Ref # / Investigator 5106
    • Naples, Florida, United States, 34102
      • Site Ref # / Investigator 11601
    • Sarasota, Florida, United States, 34239
      • Site Ref # / Investigator 6846
    • Winter Park, Florida, United States, 32789
      • Site Ref # / Investigator 3742
    • Zephyrhills, Florida, United States, 33542
      • Site Ref # / Investigator 3760
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Site Ref # / Investigator 3739
    • Macon, Georgia, United States, 31201
      • Site Ref # / Investigator 7658
  • Illinois
    • Moline, Illinois, United States, 61265
      • Site Ref # / Investigator 5397
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Site Ref # / Investigator 7453
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Site Ref # / Investigator 3759
    • Annapolis, Maryland, United States, 21401
      • Site Ref # / Investigator 3762
    • Lutherville, Maryland, United States, 21093
      • Site Ref # / Investigator 3738
  • Michigan
    • Troy, Michigan, United States, 48098
      • Site Ref # / Investigator 7472
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Site Ref # / Investigator 3744
  • Missouri
    • St. Louis, Missouri, United States, 63128
      • Site Ref # / Investigator 6088
  • New York
    • Great Neck, New York, United States, 11021
      • Site Ref # / Investigator 3756
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Site Ref # / Investigator 3752
    • Jacksonville, North Carolina, United States, 28546
      • Site Ref # / Investigator 3758
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Site Ref # / Investigator 3745
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Site Ref # / Investigator 7709
    • Tulsa, Oklahoma, United States, 74104
      • Site Ref # / Investigator 3740
  • Pennsylvania
    • Sayre, Pennsylvania, United States, 18840
      • Site Ref # / Investigator 3765
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Site Ref # / Investigator 3741
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Site Ref # / Investigator 3737
    • Nashville, Tennessee, United States, 37203
      • Site Ref # / Investigator 6077
    • Nashville, Tennessee, United States, 37205
      • Site Ref # / Investigator 5107
    • Nashville, Tennessee, United States, 37212-1610
      • Site Ref # / Investigator 3743
  • Utah
    • Ogden, Utah, United States, 84405
      • Site Ref # / Investigator 5398
  • Washington
    • Spokane, Washington, United States, 99202
      • Site Ref # / Investigator 8064
    • Spokane, Washington, United States, 99204
      • Site Ref # / Investigator 3750
  • Wisconsin
    • West Bend, Wisconsin, United States, 53095
      • Site Ref # / Investigator 3761

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants >=18 years of age and in good health (Investigator discretion) with a recent stable medical history
2. Diagnosis of UC for greater than 90 days prior to Baseline
3. Diagnosis of active UC confirmed by colonoscopy with biopsy or flexible sigmoidoscopy with biopsy during the Screening Period, with exclusion of infection

4. Active UC with a Mayo score of 6 to 12 points and endoscopy subscore of 2 to 3 points, despite concurrent treatment with at least 1 of the following (oral corticosteroids or immunosuppressants or both as defined below):

   • Stable oral corticosteroid dose (prednisone >= 20 mg/day or equivalent) for at least 14 days prior to Baseline or maintenance, corticosteroid dose (prednisone < 20 mg/day or equivalent) for at least 40 days prior to Baseline

   and/or

   • At least a 90 day course of azathioprine (AZA) or 6-mercaptopurine (6-MP) prior to Baseline, with a dose of AZA >= 1.5 mg/kg/day or 6-MP >= 1 mg/kg/day (rounded to the nearest available tablet formulation), or a dose that is the highest tolerated by the participant (e.g., due to leukopenia, elevated liver enzymes, nausea) during that time. Participant must be on a stable dose for at least 28 days prior to Baseline.

   Concurrent therapy was not required for participants who were previously treated with corticosteroids or immunosuppressants (AZA or 6-MP) during the past 5 years and in the judgment of the Investigator have failed to respond to, or could not tolerate, their treatment.

5. Participants may have been included if they had previously used an anti-tumor necrosis factor (TNF) agent (except ADA) and discontinued its use due to a loss of response or intolerance to the agent.
6. Had to be able to self-administer or had caregiver who could reliably administer subcutaneous (SC) injections.
7. Had to be able and willing to give written informed consent and to comply with the requirements of the study protocol.

8. Female had to be either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or of childbearing potential and practicing an approved method of birth control throughout the study and for 150 days after the last dose of study drug. Examples of approved methods of birth control included the following:

   • Condoms, sponge, foams, jellies, diaphragm, or intrauterine device
   • Oral, parenteral, intravaginal contraceptives for 90 days prior to study drug administration
   • A vasectomized partner The results of the serum pregnancy test performed at the Screening Visit and urine pregnancy test performed at the Baseline Visit must have been negative.
9. Judged to be in generally good health as determined by the Investigator

Exclusion Criteria:

1. History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for UC, or planned bowel surgery.
2. Received previous treatment with ADA or previous participation in an ADA clinical study.
3. Received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days of Baseline.
4. Received intravenous (IV) corticosteroids within 14 days of Screening or during the Screening Period.
5. Received therapeutic enema or suppository, other than required for endoscopy, within 14 days of the Screening endoscopy and during the remainder of the Screening Period.
6. Current diagnosis of fulminant colitis and/or toxic megacolon.
7. Disease limited to the rectum (ulcerative proctitis).
8. Current diagnosis of indeterminate colitis.
9. Current diagnosis and/or history of Crohns disease (CD).
10. Currently receiving total parenteral nutrition.
11. Used aminosalicylates for < 90 days before Baseline or not on a stable dose for at least 28 days before Baseline or discontinued use within 28 days of Baseline.
12. Positive Clostridium difficile stool assay.
13. Previously used infliximab or any anti-TNF agent within 56 days of Baseline.
14. Previously used infliximab or any anti-TNF agent without clinical response at any time ("primary non-responder") unless subject experienced a treatment-limiting reaction.
15. Infections requiring treatment with IV antibiotics, antivirals, or antifungals within 30 days of Baseline or oral antibiotics, antivirals, or antifungals within 14 days of Baseline.
16. History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix. If the Screening colonoscopy/flexible sigmoidoscopy showed evidence of dysplasia or a malignancy, subject was not to be enrolled in the study.
17. History of listeria, histoplasmosis, chronic or active hepatitis B infection, human immunodeficiency virus (HIV), immunodeficiency syndrome, central nervous system demyelinating disease, or untreated tuberculosis (TB).
18. Female subject who was pregnant or breast-feeding or considering becoming pregnant during the study (there should be at least 150 days between the last dose of study drug and either conception or initiation of breast-feeding in women of childbearing potential).
19. Poorly controlled medical condition(s), such as uncontrolled diabetes, unstable ischemic heart disease, moderate to severe congestive heart failure (CHF), recent cerebrovascular accident, and any other condition, which in the opinion of the investigator, put the subject at risk by participation in the protocol.
20. Received any investigational agent within 30 days or 5 half lives prior to Baseline (whichever was longer).
21. History of clinically significant drug or alcohol abuse during the past year.
22. Known hypersensitivity to the excipients of ADA as stated in the label.
23. Any prior exposure to Tysabri® (natalizumab), or Orencia® (abatacept) or any other biological therapy [other than Kineret® (anakinra) and anti-TNF agents].
24. Currently taking both budesonide and prednisone (or equivalent) simultaneously.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: adalimumab group	Biological: adalimumab; Prefilled syringe, 40 mg, 160 mg at Week 0, 80 mg at Week 2, and 40 mg every other week between Weeks 4 and 50.; Other Names: ABT-D2E7; Humira
Experimental: placebo group	Biological: placebo; Matching Placebo for prefilled syringe, 40 mg,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Who Achieved Clinical Remission Per Mayo Score at Week 8	Clinical remission per Mayo score is defined as a total Mayo score of at least 2 and no individual subscore greater than 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: Stool Frequency Subscore (SFS), Rectal Bleeding Subscore (RBS), Endoscopy Subscore, and Physician's Global Assessment Subscore (PGA), each of which ranges from 0 (normal) to 3 (severe disease).	Week 8
Proportion of Participants Who Achieved Clinical Remission Per Mayo Score at Week 52	Clinical remission per Mayo score is defined as a total Mayo score of at least 2 and no individual subscore greater than 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: SFS, RBS, Endoscopy Subscore, and PGA, each of which ranges from 0 (normal) to 3 (severe disease).	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Who Achieved Sustained Clinical Remission Per Mayo Score at Both Week 8 and Week 52	Clinical remission per Mayo score is defined as a total Mayo score of at least 2 and no individual subscore greater than 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: SFS, RBS, Endoscopy Subscore, and PGA, each of which ranges from 0 (normal) to 3 (severe disease).	Week 8, Week 52
Proportion of Participants Who Achieved Clinical Response Per Mayo Score at Week 8	Clinical response per Mayo score is defined as a decrease in Mayo score of at least 3 points and at least 30% from Baseline, plus either a decrease in rectal bleeding subscore (RBS) of at least 1 point from Baseline or an absolute RBS of 0 or 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: SFS, RBS, Endoscopy Subscore, and PGA, each of which ranges from 0 (normal) to 3 (severe disease).	Week 8
Proportion of Participants Who Achieved Clinical Response Per Mayo Score at Week 52	Clinical response per Mayo score is defined as a decrease in Mayo score of at least 3 points and at least 30% from Baseline, plus either a decrease in RBS of at least 1 point from Baseline or an absolute RBS of 0 or 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: SFS, RBS, Endoscopy Subscore, and PGA, each of which ranges from 0 (normal) to 3 (severe disease).	Week 52
Proportion of Participants Who Achieved Sustained Clinical Response Per Mayo Score at Both Week 8 and Week 52	Clinical response per Mayo score is defined as a decrease in Mayo score of at least 3 points and at least 30% from Baseline, plus either a decrease in RBS of at least 1 point from Baseline or an absolute RBS of 0 or 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: SFS, RBS, Endoscopy Subscore, and PGA, each of which ranges from 0 (normal) to 3 (severe disease).	Week 8, Week 52
Proportion of Participants Who Achieved Mucosal Healing at Week 8	Mucosal healing is defined as an Endoscopy Subscore of 0 or 1 as assessed by flexible sigmoidoscopy. Possible scores range from 0-3 as follows: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions), 3 = Severe disease(spontaneous bleeding, ulceration).	Week 8
Proportion of Participants Who Achieved Mucosal Healing at Week 52	Mucosal healing is defined as an Endoscopy Subscore of 0 or 1 as assessed by flexible sigmoidoscopy. Possible scores range from 0-3 as follows: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions), 3 = Severe disease(spontaneous bleeding, ulceration).	Week 52
Proportion of Participants Who Achieved Sustained Mucosal Healing at Both Week 8 and Week 52	Mucosal healing is defined as an Endoscopy Subscore of 0 or 1 as assessed by flexible sigmoidoscopy. Possible scores range from 0-3 as follows: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions), 3 = Severe disease(spontaneous bleeding, ulceration).	Week 8, Week 52
Proportion of Participants Who Discontinued Corticosteroid Use Before Week 52 and Achieved Clinical Remission Per Mayo Score at Week 52	Clinical remission per Mayo score is defined as a total Mayo score of at least 2 and no individual subscore greater than 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: SFS, RBS, Endoscopy Subscore, and PGA, each of which ranges from 0 (normal) to 3 (severe disease).	Baseline to Week 52
Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (a Score of 0 or 1) at Week 8	The PGA includes the 3 other subscores (SFS, RBS, and Endoscopy), the participant's daily record of abdominal discomfort and functional assessment, and other observations such as physical findings and the participant's performance status. Possible scores range from 0-3 as follows: 0 = Normal (other subscores are 0), 1 = Mild disease (other subscores are mostly 1), 2 = Moderate disease (other subscores are 1 to 2), 3 = Severe disease (other subscores are 2 to 3).	Week 8
Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (a Score of 0 or 1) at Week 8	SFS ranges from 0-3 as follows: 0 = Normal number of stools for this participant, 1 = 1-2 stools more than normal, 2 = 3-4 stools more than normal, 3 = 5 or more stools more than normal. The participant served as his/her own control.	Week 8
Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (a Score of 0 or 1) at Week 8	RBS ranges from 0-3 as follows: 0 = no blood seen, 1 = streaks of blood with stool less than half the time, 2 = obvious blood with stool most of the time, 3 = blood alone passed	Week 8
Proportion of Participants Who Discontinued Corticosteroid Use for At Least 90 Days and Achieved Clinical Remission Per Mayo Score at Week 52	Clinical remission per Mayo score is defined as a total Mayo score of at least 2 and no individual subscore greater than 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: SFS, RBS, Endoscopy Subscore, and PGA, each of which ranges from 0 (normal) to 3 (severe disease).	Baseline to Week 52
Proportion of Participants Who Discontinued Corticosteroid Use and Achieved Clinical Remission Per Mayo Score (Sustained) at Both Weeks 32 and 52	Clinical remission per Mayo score is defined as a total Mayo score of at least 2 and no individual subscore greater than 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: SFS, RBS, Endoscopy Subscore, and PGA, each of which ranges from 0 (normal) to 3 (severe disease).	Week 32, Week 52
Proportion of Inflammatory Bowel Disease Questionnaire Responders at Week 52	Response per the Inflammatory Bowel Disease Questionnaire (IBDQ) was defined as at least a 16-point increase from Baseline in total IBDQ score. The IBDQ is a 32-item questionnaire consisting of 4 dimensions: bowel-related symptoms, systemic function, social function, and emotional status. The responses to questions within each domain range from 1 (significant impairment) to 7 (no impairment), with total score ranging from 32 (very poor) to 224 (perfect health-related quality of life).	Week 52
Proportion of Inflammatory Bowel Disease Questionnaire Responders at Week 8	Response per the Inflammatory Bowel Disease Questionnaire (IBDQ) was defined as at least a 16-point increase from Baseline in total IBDQ score. The IBDQ is a 32-item questionnaire consisting of 4 dimensions: bowel-related symptoms, systemic function, social function, and emotional status. The responses to questions within each domain range from 1 (significant impairment) to 7 (no impairment), with total score ranging from 32 (very poor) to 224 (perfect health-related quality of life).	Week 8

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Roopal B Thakkar, M.D., Abbott

Publications and helpful links

General Publications

• Ryan C, Sobell JM, Leonardi CL, Lynde CW, Karunaratne M, Valdecantos WC, Hendrickson BA. Safety of Adalimumab Dosed Every Week and Every Other Week: Focus on Patients with Hidradenitis Suppurativa or Psoriasis. Am J Clin Dermatol. 2018 Jun;19(3):437-447. doi: 10.1007/s40257-017-0341-6.
• Wolf D, D'Haens G, Sandborn WJ, Colombel JF, Van Assche G, Robinson AM, Lazar A, Zhou Q, Petersson J, Thakkar RB. Escalation to weekly dosing recaptures response in adalimumab-treated patients with moderately to severely active ulcerative colitis. Aliment Pharmacol Ther. 2014 Sep;40(5):486-97. doi: 10.1111/apt.12863. Epub 2014 Jul 15.
• Feagan BG, Sandborn WJ, Lazar A, Thakkar RB, Huang B, Reilly N, Chen N, Yang M, Skup M, Mulani P, Chao J. Adalimumab therapy is associated with reduced risk of hospitalization in patients with ulcerative colitis. Gastroenterology. 2014 Jan;146(1):110-118.e3. doi: 10.1053/j.gastro.2013.09.032. Epub 2013 Sep 22.
• Sandborn WJ, Colombel JF, D'Haens G, Van Assche G, Wolf D, Kron M, Lazar A, Robinson AM, Yang M, Chao JD, Thakkar R. One-year maintenance outcomes among patients with moderately-to-severely active ulcerative colitis who responded to induction therapy with adalimumab: subgroup analyses from ULTRA 2. Aliment Pharmacol Ther. 2013 Jan;37(2):204-13. doi: 10.1111/apt.12145. Epub 2012 Nov 23.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: December 5, 2006
• First Submitted That Met QC Criteria: December 5, 2006
• First Posted (Estimate): December 7, 2006

Study Record Updates

• Last Update Posted (Estimate): May 3, 2011
• Last Update Submitted That Met QC Criteria: April 28, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; Adalimumab; TNF Antagonist; Mayo Score
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: M06-827; 2006-002782-40 (EudraCT Number)