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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00408629




Registration number
NCT00408629
Ethics application status
Date submitted
5/12/2006
Date registered
7/12/2006
Date last updated
3/05/2011

Titles & IDs
Public title
Efficacy and Safety of Adalimumab in Subjects With Moderately to Severely Active Ulcerative Colitis
Scientific title
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
Secondary ID [1] 0 0
2006-002782-40
Secondary ID [2] 0 0
M06-827
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - adalimumab
Treatment: Other - placebo

Experimental: adalimumab group -

Experimental: placebo group -


Treatment: Other: 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.

Treatment: Other: placebo
Matching Placebo for prefilled syringe, 40 mg,
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of Participants Who Achieved Clinical Remission Per Mayo Score at Week 8
Timepoint [1] 0 0
Week 8
Primary outcome [2] 0 0
Proportion of Participants Who Achieved Clinical Remission Per Mayo Score at Week 52
Timepoint [2] 0 0
Week 52
Secondary outcome [1] 0 0
Proportion of Participants Who Achieved Sustained Clinical Remission Per Mayo Score at Both Week 8 and Week 52
Timepoint [1] 0 0
Week 8, Week 52
Secondary outcome [2] 0 0
Proportion of Participants Who Achieved Clinical Response Per Mayo Score at Week 8
Timepoint [2] 0 0
Week 8
Secondary outcome [3] 0 0
Proportion of Participants Who Achieved Clinical Response Per Mayo Score at Week 52
Timepoint [3] 0 0
Week 52
Secondary outcome [4] 0 0
Proportion of Participants Who Achieved Sustained Clinical Response Per Mayo Score at Both Week 8 and Week 52
Timepoint [4] 0 0
Week 8, Week 52
Secondary outcome [5] 0 0
Proportion of Participants Who Achieved Mucosal Healing at Week 8
Timepoint [5] 0 0
Week 8
Secondary outcome [6] 0 0
Proportion of Participants Who Achieved Mucosal Healing at Week 52
Timepoint [6] 0 0
Week 52
Secondary outcome [7] 0 0
Proportion of Participants Who Achieved Sustained Mucosal Healing at Both Week 8 and Week 52
Timepoint [7] 0 0
Week 8, Week 52
Secondary outcome [8] 0 0
Proportion of Participants Who Discontinued Corticosteroid Use Before Week 52 and Achieved Clinical Remission Per Mayo Score at Week 52
Timepoint [8] 0 0
Baseline to Week 52
Secondary outcome [9] 0 0
Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (a Score of 0 or 1) at Week 8
Timepoint [9] 0 0
Week 8
Secondary outcome [10] 0 0
Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (a Score of 0 or 1) at Week 8
Timepoint [10] 0 0
Week 8
Secondary outcome [11] 0 0
Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (a Score of 0 or 1) at Week 8
Timepoint [11] 0 0
Week 8
Secondary outcome [12] 0 0
Proportion of Participants Who Discontinued Corticosteroid Use for At Least 90 Days and Achieved Clinical Remission Per Mayo Score at Week 52
Timepoint [12] 0 0
Baseline to Week 52
Secondary outcome [13] 0 0
Proportion of Participants Who Discontinued Corticosteroid Use and Achieved Clinical Remission Per Mayo Score (Sustained) at Both Weeks 32 and 52
Timepoint [13] 0 0
Week 32, Week 52
Secondary outcome [14] 0 0
Proportion of Inflammatory Bowel Disease Questionnaire Responders at Week 52
Timepoint [14] 0 0
Week 52
Secondary outcome [15] 0 0
Proportion of Inflammatory Bowel Disease Questionnaire Responders at Week 8
Timepoint [15] 0 0
Week 8

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2010
Sample size
Target
Accrual to date
Final
518
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Site Ref # / Investigator 13722 - Garran
Recruitment hospital [2] 0 0
Site Ref # / Investigator 16141 - Bankstown
Recruitment hospital [3] 0 0
Site Ref # / Investigator 13723 - Herston
Recruitment hospital [4] 0 0
Site Ref # / Investigator 10706 - Bedford Park
Recruitment hospital [5] 0 0
Site Ref # / Investigator 14882 - Box Hill
Recruitment hospital [6] 0 0
Site Ref # / Investigator 9002 - Malvern
Recruitment hospital [7] 0 0
Site Ref # / Investigator 10704 - Fremantle
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
NSW 2200 - Bankstown
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
SA 5042 - Bedford Park
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
3144 - Malvern
Recruitment postcode(s) [7] 0 0
6160 - Fremantle
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
United States of America
State/province [21] 0 0
Wisconsin
Country [22] 0 0
Argentina
State/province [22] 0 0
Buenos Aires
Country [23] 0 0
Austria
State/province [23] 0 0
Vienna
Country [24] 0 0
Belgium
State/province [24] 0 0
Bonheiden
Country [25] 0 0
Belgium
State/province [25] 0 0
Brussels
Country [26] 0 0
Belgium
State/province [26] 0 0
Ghent
Country [27] 0 0
Belgium
State/province [27] 0 0
Leuven
Country [28] 0 0
Canada
State/province [28] 0 0
British Columbia
Country [29] 0 0
Canada
State/province [29] 0 0
Ontario
Country [30] 0 0
Canada
State/province [30] 0 0
Quebec
Country [31] 0 0
Czech Republic
State/province [31] 0 0
Ceske Budejovice
Country [32] 0 0
Czech Republic
State/province [32] 0 0
Hradec Kravlove 12
Country [33] 0 0
Czech Republic
State/province [33] 0 0
Olomouc
Country [34] 0 0
Czech Republic
State/province [34] 0 0
Prague 4
Country [35] 0 0
Czech Republic
State/province [35] 0 0
Prague 5
Country [36] 0 0
Denmark
State/province [36] 0 0
Hvidovre
Country [37] 0 0
Denmark
State/province [37] 0 0
Odense C
Country [38] 0 0
France
State/province [38] 0 0
Clichy
Country [39] 0 0
France
State/province [39] 0 0
Lille Cedex
Country [40] 0 0
France
State/province [40] 0 0
Pessac Cedex
Country [41] 0 0
France
State/province [41] 0 0
Toulouse
Country [42] 0 0
Germany
State/province [42] 0 0
Hamburg
Country [43] 0 0
Germany
State/province [43] 0 0
Magdeburg
Country [44] 0 0
Germany
State/province [44] 0 0
Minden
Country [45] 0 0
Germany
State/province [45] 0 0
Muenster
Country [46] 0 0
Germany
State/province [46] 0 0
Munich
Country [47] 0 0
Germany
State/province [47] 0 0
Regensburg
Country [48] 0 0
Hungary
State/province [48] 0 0
Budapest
Country [49] 0 0
Hungary
State/province [49] 0 0
Debrecen
Country [50] 0 0
Hungary
State/province [50] 0 0
Gyula
Country [51] 0 0
Hungary
State/province [51] 0 0
Miskoic
Country [52] 0 0
Hungary
State/province [52] 0 0
Miskolc
Country [53] 0 0
Israel
State/province [53] 0 0
Kfar Saba
Country [54] 0 0
Israel
State/province [54] 0 0
Petah Tikva
Country [55] 0 0
Israel
State/province [55] 0 0
Tel Aviv
Country [56] 0 0
New Zealand
State/province [56] 0 0
Auckland
Country [57] 0 0
New Zealand
State/province [57] 0 0
Christchurch
Country [58] 0 0
New Zealand
State/province [58] 0 0
Hamilton
Country [59] 0 0
Norway
State/province [59] 0 0
Gjovik
Country [60] 0 0
Norway
State/province [60] 0 0
Oslo
Country [61] 0 0
Norway
State/province [61] 0 0
Tromso
Country [62] 0 0
Norway
State/province [62] 0 0
Trondheim
Country [63] 0 0
Poland
State/province [63] 0 0
Lodz
Country [64] 0 0
Poland
State/province [64] 0 0
Warsaw
Country [65] 0 0
Poland
State/province [65] 0 0
Wroclaw
Country [66] 0 0
Portugal
State/province [66] 0 0
Faro
Country [67] 0 0
Portugal
State/province [67] 0 0
Lisbon
Country [68] 0 0
Spain
State/province [68] 0 0
Barcelona
Country [69] 0 0
Spain
State/province [69] 0 0
Madrid
Country [70] 0 0
Switzerland
State/province [70] 0 0
Basel
Country [71] 0 0
Switzerland
State/province [71] 0 0
Bern
Country [72] 0 0
Switzerland
State/province [72] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Abbott
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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).
Trial website
https://clinicaltrials.gov/study/NCT00408629
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Roopal B Thakkar, M.D.
Address 0 0
Abbott
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00408629