Ulcerative ColitisPhase 3NCT00408629
Efficacy and Safety of Adalimumab in Subjects With Moderately to Severely Active Ulcerative Colitis
A Phase 3 study testing adalimumab in people with Ulcerative Colitis, run by Abbott at 108 sites in 18 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- adalimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 518 participants
- Where
- 108 sitesin 18 countries
- Study dates
- Nov 2006to Mar 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants >=18 years of age and in good health (Investigator discretion) with a recent stable medical history
- Diagnosis of UC for greater than 90 days prior to Baseline
- Diagnosis of active UC confirmed by colonoscopy with biopsy or flexible sigmoidoscopy with biopsy during the Screening Period, with exclusion of infection
- 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
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- 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.
- 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.
- Had to be able to self-administer or had caregiver who could reliably administer subcutaneous (SC) injections.
- Had to be able and willing to give written informed consent and to comply with the requirements of the study protocol.
- 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.
- Judged to be in generally good health as determined by the Investigator
Who cannot join
- History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for UC, or planned bowel surgery.
- Received previous treatment with ADA or previous participation in an ADA clinical study.
- Received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days of Baseline.
- Received intravenous (IV) corticosteroids within 14 days of Screening or during the Screening Period.
- 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.
- Current diagnosis of fulminant colitis and/or toxic megacolon.
Show all 24Show fewer
- Disease limited to the rectum (ulcerative proctitis).
- Current diagnosis of indeterminate colitis.
- Current diagnosis and/or history of Crohns disease (CD).
- Currently receiving total parenteral nutrition.
- 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.
- Positive Clostridium difficile stool assay.
- Previously used infliximab or any anti-TNF agent within 56 days of Baseline.
- Previously used infliximab or any anti-TNF agent without clinical response at any time ("primary non-responder") unless subject experienced a treatment-limiting reaction.
- 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.
- 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.
- 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).
- 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).
- 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.
- Received any investigational agent within 30 days or 5 half lives prior to Baseline (whichever was longer).
- History of clinically significant drug or alcohol abuse during the past year.
- Known hypersensitivity to the excipients of ADA as stated in the label.
- Any prior exposure to Tysabri® (natalizumab), or Orencia® (abatacept) or any other biological therapy [other than Kineret® (anakinra) and anti-TNF agents].
- Currently taking both budesonide and prednisone (or equivalent) simultaneously.
Trial locations and contacts
108 sites in 18 countries.
108 sites in 18 countries
United States36 sites
Site Ref # / Investigator 5394
Anaheim, California, 92801
Site Ref # / Investigator 3759
Annapolis, Maryland, 21401
Site Ref # / Investigator 3762
Annapolis, Maryland, 21401
Site Ref # / Investigator 3739
Atlanta, Georgia, 30342
Site Ref # / Investigator 3752
Charlotte, North Carolina, 28207
Site Ref # / Investigator 3745
Cincinnati, Ohio, 45219
Site Ref # / Investigator 3741
Columbia, South Carolina, 29204
Site Ref # / Investigator 12903
Gainesville, Florida, 32607
Site Ref # / Investigator 3737
Germantown, Tennessee, 38138
Site Ref # / Investigator 3756
Great Neck, New York, 11021
Site Ref # / Investigator 3754
Hamden, Connecticut, 06518
Site Ref # / Investigator 3747
Hollywood, Florida, 33021
Site Ref # / Investigator 5106
Jacksonville, Florida, 32256
Site Ref # / Investigator 3758
Jacksonville, North Carolina, 28546
Site Ref # / Investigator 3738
Lutherville, Maryland, 21093
Site Ref # / Investigator 7658
Macon, Georgia, 31201
Site Ref # / Investigator 5397
Moline, Illinois, 61265
Site Ref # / Investigator 11601
Naples, Florida, 34102
Site Ref # / Investigator 6077
Nashville, Tennessee, 37203
Site Ref # / Investigator 5107
Nashville, Tennessee, 37205
Site Ref # / Investigator 3743
Nashville, Tennessee, 37212-1610
Site Ref # / Investigator 5398
Ogden, Utah, 84405
Site Ref # / Investigator 7709
Oklahoma City, Oklahoma, 73104
Site Ref # / Investigator 3744
Rochester, Minnesota, 55905
Site Ref # / Investigator 6846
Sarasota, Florida, 34239
Site Ref # / Investigator 3765
Sayre, Pennsylvania, 18840
Site Ref # / Investigator 8064
Spokane, Washington, 99202
Site Ref # / Investigator 3750
Spokane, Washington, 99204
Site Ref # / Investigator 6088
St Louis, Missouri, 63128
Site Ref # / Investigator 7453
Topeka, Kansas, 66606
Site Ref # / Investigator 7472
Troy, Michigan, 48098
Site Ref # / Investigator 3740
Tulsa, Oklahoma, 74104
Site Ref # / Investigator 3761
West Bend, Wisconsin, 53095
Site Ref # / Investigator 3753
Wheat Ridge, Colorado, 80033
Site Ref # / Investigator 3742
Winter Park, Florida, 32789
Site Ref # / Investigator 3760
Zephyrhills, Florida, 33542
Canada9 sites
Site Ref # / Investigator 13556
Greater Sudbury, Ontario, P3E 2N8
Site Ref # / Investigator 3769
Hamilton, Ontario, L8N 3Z5
Site Ref # / Investigator 10423
Kelowna, British Columbia, B1Y 1Z9
Site Ref # / Investigator 3771
Montreal, Quebec, H3A 1A1
Site Ref # / Investigator 3764
Montreal, Quebec, H3G 1A4
Site Ref # / Investigator 3768
Montreal, Quebec, H3T 1E2
Site Ref # / Investigator 3770
Québec, Quebec, G1S 4L8
Site Ref # / Investigator 3736
Toronto, Ontario, M5G 1X5
Site Ref # / Investigator 3766
Victoria, British Columbia, V8T 5G4
Germany8 sites
Site Ref # / Investigator 15321
Hamburg, 20148
Site Ref # / Investigator 9069
Hamburg, 22559
Site Ref # / Investigator 14642
Magdeburg, 39120
Site Ref # / Investigator 9067
Minden, 32423
Site Ref # / Investigator 14661
Munich, 80639
Site Ref # / Investigator 9801
Munich, 81377
Site Ref # / Investigator 14761
Münster, 48159
Site Ref # / Investigator 5247
Regensburg, 93053
Australia7 sites
Site Ref # / Investigator 16141
Bankstown, New South Wales, NSW 2200
Site Ref # / Investigator 10706
Bedford Park, South Australia, SA 5042
Site Ref # / Investigator 14882
Box Hill, Victoria, 3128
Site Ref # / Investigator 10704
Fremantle, Western Australia, 6160
Site Ref # / Investigator 13722
Garran, Australian Capital Territory, 2605
Site Ref # / Investigator 13723
Herston, Queensland, 4029
Site Ref # / Investigator 9002
Malvern, Victoria, 3144
Hungary6 sites
Site Ref # / Investigator 7485
Budapest, H-1076
Site Ref # / Investigator 5025
Budapest, H-1135
Site Ref # / Investigator 10625
Debrecen, 4032
Site Ref # / Investigator 14104
Gyula, 5700
Site Ref # / Investigator 4987
Miskoic, H-3051
Site Ref # / Investigator 5036
Miskolc, H-3526
Belgium5 sites
Site Ref # / Investigator 5256
Bonheiden, 2820
Site Ref # / Investigator 5253
Brussels, 1070
Site Ref # / Investigator 6225
Brussels, 1200
Site Ref # / Investigator 6079
Ghent, 9000
Site Ref # / Investigator 6078
Leuven, 3000
Czechia5 sites
Site Ref # / Investigator 7021
České Budějovice, 370 87
Site Ref # / Investigator 6307
Hradec Kravlove 12, 500 12
Site Ref # / Investigator 6606
Olomouc, 775 20
Site Ref # / Investigator 7481
Prague, 140 21
Site Ref # / Investigator 7479
Prague, 15006
Norway5 sites
Site Ref # / Investigator 9561
Gjøvik, 2819
Site Ref # / Investigator 5197
Oslo, 0027
Site Ref # / Investigator 6297
Oslo, 0514
Site Ref # / Investigator 5194
Tromsø, 9038
Site Ref # / Investigator 5193
Trondheim, 7006
France4 sites
Site Ref # / Investigator 6231
Clichy, 92110
Site Ref # / Investigator 7476
Lille, 59037
Site Ref # / Investigator 7475
Pessac, 33600
Site Ref # / Investigator 7474
Toulouse, 31059
New Zealand4 sites
Site Ref # / Investigator 13301
Auckland, 0620
Site Ref # / Investigator 13181
Auckland, 1148
Site Ref # / Investigator 13148
Christchurch, 8011
Site Ref # / Investigator 13482
Hamilton
Poland4 sites
Site Ref # / Investigator 5242
Lodz, 90-153
Site Ref # / Investigator 5266
Warsaw, 02 781
Site Ref # / Investigator 5265
Warsaw, 02-507
Site Ref # / Investigator 15263
Wroclaw, 54-144
Israel3 sites
Site Ref # / Investigator 12744
Kfar Saba, 44281
Site Ref # / Investigator 10623
Petah Tikva, 49100
Site Ref # / Investigator 15361
Tel Aviv, 64239
Portugal3 sites
Site Ref # / Investigator 5264
Faro, 8000-386
Site Ref # / Investigator 7473
Lisbon, 1150-314
Site Ref # / Investigator 5263
Lisbon, 1769-001
Switzerland3 sites
Site Ref # / Investigator 10221
Basel, 4031
Site Ref # / Investigator 10222
Bern, 3010
Site Ref # / Investigator 9162
Zurich, 8091
Denmark2 sites
Site Ref # / Investigator 6483
Hvidovre, DK-2650
Site Ref # / Investigator 7477
Odense C, 5000
Spain2 sites
Site Ref # / Investigator 5211
Barcelona, 08036
Site Ref # / Investigator 5212
Madrid, 28040
About this study
Official 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
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).
Read the 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.
- Conditions
- Ulcerative Colitis
- Being tested
- adalimumab, placebo
- Keywords
- Ulcerative Colitis, Adalimumab, TNF Antagonist, Mayo Score
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
adalimumabBiological
Also called ABT-D2E7, Humira
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.
placeboBiological
Matching Placebo for prefilled syringe, 40 mg,
| Study group | Role | What they receive |
|---|---|---|
| adalimumab group | Experimental | Not described Receives: Biological: adalimumab |
| placebo group | Experimental | Not described Receives: Biological: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: Week 52
Secondary outcomes (15)
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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2006 (estimated)
- Study startNov 2006
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 518 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abbott
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Roopal B Thakkar, M.D., Study director, Abbott
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00408629
- Sponsor's protocol ID
- M06-827
- Other IDs
- 2006-002782-40
- Status last verified
- Apr 2011
- First submitted
- 5 Dec 2006
- Last updated
- 3 May 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 29380251Wolf 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.
PubMed 25041859Feagan 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.
PubMed 24067881Sandborn 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.
PubMed 23173821
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT00408629
- Acronym / sponsor ID
- M06-827
- Conditions
- Ulcerative Colitis
- Keywords
- Ulcerative Colitis, Adalimumab, TNF Antagonist, Mayo Score
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 518 participants (actual)
- Lead sponsor
- AbbottIndustry (pharma, biotech, devices)
- Study start
- Nov 2006
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 7 Dec 2006 (estimated)
- Results
- Posted 31 Mar 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| adalimumab group | Experimental | Biological: adalimumab |
| placebo group | Experimental | Biological: placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Participants >=18 years of age and in good health (Investigator discretion) with a recent stable medical history
- Diagnosis of UC for greater than 90 days prior to Baseline
- Diagnosis of active UC confirmed by colonoscopy with biopsy or flexible sigmoidoscopy with biopsy during the Screening Period, with exclusion of infection
- 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):
- and/or
Key exclusion criteria (24 listed)
- History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for UC, or planned bowel surgery.
- Received previous treatment with ADA or previous participation in an ADA clinical study.
- Received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days of Baseline.
- Received intravenous (IV) corticosteroids within 14 days of Screening or during the Screening Period.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| adalimumabAlso: ABT-D2E7, HumiraPrefilled syringe, 40 mg, 160 mg at Week 0, 80 mg at Week 2, and 40 mg every other week between Weeks 4 and 50. | Biological | adalimumab group |
| placeboMatching Placebo for prefilled syringe, 40 mg, | Biological | placebo group |
Primary outcome
Proportion of Participants Who Achieved Clinical Remission Per Mayo Score at Week 8
Time frame: 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).
Proportion of Participants Who Achieved Clinical Remission Per Mayo Score at Week 52
Time frame: 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).
15 secondary outcomes
Proportion of Participants Who Achieved Sustained Clinical Remission Per Mayo Score at Both Week 8 and Week 52
Time frame: Week 8, Week 52
Proportion of Participants Who Achieved Clinical Response Per Mayo Score at Week 8
Time frame: Week 8
Proportion of Participants Who Achieved Clinical Response Per Mayo Score at Week 52
Time frame: Week 52
Proportion of Participants Who Achieved Sustained Clinical Response Per Mayo Score at Both Week 8 and Week 52
Time frame: Week 8, Week 52
Proportion of Participants Who Achieved Mucosal Healing at Week 8
Time frame: Week 8
Proportion of Participants Who Achieved Mucosal Healing at Week 52
Time frame: Week 52
Proportion of Participants Who Achieved Sustained Mucosal Healing at Both Week 8 and Week 52
Time frame: Week 8, Week 52
Proportion of Participants Who Discontinued Corticosteroid Use Before Week 52 and Achieved Clinical Remission Per Mayo Score at Week 52
Time frame: 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
Time frame: Week 8
Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (a Score of 0 or 1) at Week 8
Time frame: Week 8
Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (a Score of 0 or 1) at Week 8
Time frame: Week 8
Proportion of Participants Who Discontinued Corticosteroid Use for At Least 90 Days and Achieved Clinical Remission Per Mayo Score at Week 52
Time frame: 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
Time frame: Week 32, Week 52
Proportion of Inflammatory Bowel Disease Questionnaire Responders at Week 52
Time frame: Week 52
Proportion of Inflammatory Bowel Disease Questionnaire Responders at Week 8
Time frame: Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29380251Ryan 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.
- Derived from this study: PubMed 25041859Wolf 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.
- Derived from this study: PubMed 24067881Feagan 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.
- Derived from this study: PubMed 23173821Sandborn 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roopal B Thakkar, M.D. study director
Abbott
108 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing adalimumab in people with Ulcerative Colitis, run by Abbott at 108 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 108 sites in United States, Canada, Germany, Australia, Hungary and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Mar 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Who Achieved Clinical Remission Per Mayo Score at Week 8 (time frame: Week 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00408629, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2011.