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

Ulcerative Colitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00385736
• Other study ID #: M06-826
• Secondary ID: 2006-002781-20
• Status: Completed
• Phase: Phase 3
• First received: October 9, 2006
• Last updated: April 7, 2011
• Start date: November 2006
• Est. completion date: March 2010

Study information

• Verified date: April 2011
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria : Federal Ministry for Labour, Health, and Social AffairsAustria: Agency for Health and Food SafetyBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentCanada: Health CanadaCzech Republic: State Institute for Drug ControlGermany: Ministry of HealthGermany: Paul-Ehrlich-InstitutHungary: National Institute of PharmacyItaly: Ministry of HealthItaly: The Italian Medicines AgencyNetherlands: Medicines Evaluation Board (MEB)Poland: Ministry of HealthPoland: Ministry of Science and Higher EducationSlovak Republic: Ethics CommitteeSlovakia: State Institute for Drug ControlSweden: Medical Products AgencyUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to assess the efficacy and safety of adalimumab for the induction of clinical remission in subjects with moderately to severely active ulcerative colitis.

Description:

This was a Phase 3, multicenter, randomized, double-blind (DB), placebo-controlled trial designed to evaluate the efficacy and safety of the human anti-TNF monoclonal antibody adalimumab for the induction of clinical remission in participants with moderately to severely active ulcerative colitis (UC).

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 by flexible sigmoidoscopy with biopsy, were enrolled at 80 sites worldwide. The study enrolled 576 participants, including 186 participants under the original protocol and protocol Amendments 1 and 2, and 390 participants under protocol Amendments 3 and 4.

Participants enrolled in the study prior to Amendment 3 were randomized in a 1:1 ratio to receive adalimumab or placebo during the 12-week DB induction period. Participants received 4 injections of adalimumab 40 mg (160 mg) or 4 injections of placebo at Baseline (Week 0), followed by 2 injections of adalimumab 40 mg (80 mg) or 2 injections of placebo at Week 2, followed by 1 injection of adalimumab 40 mg or placebo at Weeks 4 and 6. At Week 8, participants randomized to placebo received 4 injections of adalimumab 40 mg (160 mg) followed by 2 injections of adalimumab 40 mg (80 mg) at Week 10. Participants randomized to adalimumab received 3 injections of placebo and 1 injection of adalimumab 40 mg at Week 8 and 1 injection of placebo and 1 injection of adalimumab 40 mg at Week 10. All participants continued to receive 1 injection of open-label (OL) adalimumab 40 mg every other week beginning at Week 12 up to Week 52 (or the early termination visit). Starting at Week 14, participants who had inadequate responses to treatment (as defined using partial Mayo scores) were permitted to dose escalate to adalimumab 40 mg weekly. Participants with persistent inadequate response while on weekly treatment could be discontinued from the study at the discretion of the investigator.

In August 2007, the study design was amended to incorporate an additional adalimumab induction dosing arm of 80/40 mg. Earlier that year, both 160/80-mg and 80/40-mg induction regimens had been approved in the EU as induction treatment for Crohn's disease. The adalimumab induction dosing regimen of 80/40 mg was therefore included so that both of these approved induction regimens would be evaluated for the induction of remission of UC.

Participants enrolled in the study after Amendment 3 were randomized in a 1:1:1 ratio to receive adalimumab (1 of 2 regimens) or placebo during the 8-week DB induction period. Participants received DB therapy from Baseline until Week 8 and OL therapy from Week 8 until the end of the study. In the first adalimumab dosing arm (adalimumab 80/40), participants received 2 injections of adalimumab 40 mg (80 mg) and 2 injections of placebo at Baseline followed by 1 injection of adalimumab 40 mg and 1 injection of placebo at Week 2, and 1 injection of adalimumab 40 mg every other week thereafter. In the second adalimumab DB induction dosing arm (adalimumab 160/80), participants received 4 injections of adalimumab 40 mg (160 mg) at Baseline followed by 2 injections of adalimumab 40 mg (80 mg) at Week 2, and 1 injection of adalimumab 40 mg every other week thereafter. Participants randomized to placebo received 4 injections of placebo at Baseline followed by 2 injections of placebo at Week 2, and 1 injection of placebo at Weeks 4 and 6. Beginning at Week 8, but after the Week 8 study assessments had been completed, all participants received 1 injection of OL adalimumab 40 mg every other week until Week 52 or early termination. Starting at Week 12, participants who had inadequate responses to treatment (as defined using partial Mayo scores) were permitted to dose escalate to adalimumab 40 mg weekly. Participants with persistent inadequate response while on weekly treatment could be discontinued from the study at the discretion of the investigator.

For the analysis of efficacy parameters during the DB Period through Week 8, only participants randomized under Protocol Amendment 3 or later were considered ("Efficacy Analysis Set - Induction" in the participant flow). For the analysis of efficacy parameters during the OL Period through Week 52, all randomized participants (under any version of the protocol) who received at least 1 dose of study drug were considered ("Efficacy Analysis Set

• Maintenance" in the participant flow). For the analysis of safety parameters, all participants who received at least 1 dose of study drug were considered ("Safety Analysis Set" in the participant flow).

Twelve ranked secondary variables during the DB Period through Week 8 were to be tested in a hierarchical order to account for multiple testing. These variables are identified as "Ranked Secondary Endpoints" in the results section below. Additionally, non-ranked secondary variables during the OL Period through Week 52 were tested and are presented after the ranked secondary endpoints in the results section below.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 576
• Est. completion date: March 2010
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

The following eligibility criteria applied to participants enrolled following Amendment 3 to the study protocol.

Inclusion Criteria:

1. Male and female participants >= 18 years of age

2. Diagnosis of ulcerative colitis for greater than 90 days prior to Baseline

3. Diagnosis of active ulcerative colitis 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 dose of >= 20 mg/day or equivalent) for at least 14 days prior to Baseline or stable oral corticosteroid dose (prednisone of < 20 mg/day) for at least 40 days prior to Baseline.

and/or

• At least a consecutive 90 day course of azathioprine or 6-mercaptopurine (6 MP) prior to Baseline, with a dose of azathioprine >= 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 was to 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 (azathioprine or 6-MP) during the previous 5 years and, in the judgment of the investigator, have failed to respond to or could not tolerate their treatment.

5. Had to be able to self-administer or has caregiver who can reliably administer subcutaneous injections.

6. Had to be able and willing to give written informed consent and to comply with the requirements of this study protocol.

7. 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 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 or intravaginal contraceptives for 90 days prior to study drug administration

• A vasectomized partner

8. The results of the serum pregnancy test performed at the Screening Visit and urine pregnancy test performed at the Baseline Visit had to be negative.

9. Judged to be in generally good health as determined by the principal investigator

Exclusion Criteria:

1. History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for ulcerative colitis or is planning bowel surgery.

2. Received infliximab or any other anti-TNF agent or any biological therapy in the past.

3. Received previous treatment with adalimumab or previous participation in an adalimumab clinical study.

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

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

6. Received therapeutic enema or suppository, other than required for endoscopy, within 14 days prior to the Screening endoscopy and during the remainder of the Screening Period.

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

8. Participants with disease limited to the rectum (ulcerative proctitis).

9. Current diagnosis of indeterminate colitis.

10. Current diagnosis and/or history of Crohn's disease.

11. Currently receiving total parenteral nutrition.

12. Discontinued use of azathioprine or 6-MP within 28 days of Baseline.

13. Discontinued use of corticosteroid within 14 days of Baseline.

14. Participants using aminosalicylates for less than 90 days prior to Baseline, not on a stable dose for at least 28 days prior to Baseline, or discontinued use within 28 days of Baseline.

15. Participants with positive Clostridium difficile stool assay.

16. Infections requiring treatment with intravenous (IV) antibiotics, IV antivirals, or IV antifungals within 30 days prior to Baseline or oral antibiotics, oral antivirals, or oral antifungals within 14 days prior to Baseline.

17. 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, the participant was not to be enrolled in the study.

18. History of listeria, histoplasmosis, chronic or active hepatitis B infection, human immunodeficiency virus, immunodeficiency syndrome, central nervous system demyelinating disease, or untreated tuberculosis (TB).

19. Female participants who was pregnant or breast-feeding or considering becoming pregnant during the study. There should be at least a 150-day period between the last dose of study drug and either conception or initiation of breast-feeding in women of childbearing potential.

20. Poorly controlled medical condition(s), such as uncontrolled diabetes, unstable ischemic heart disease, moderate to severe congestive heart failure, recent cerebrovascular accident and any other condition, which in the opinion of the investigator, would put the participant at risk by participation in the protocol.

21. Received any investigational agent within 30 days or 5 half lives prior to Baseline (whichever is longer).

22. History of clinically significant drug or alcohol abuse during the previous year.

23. Participants with known hypersensitivity to the excipients of adalimumab as stated in the label.

24. Participants with any prior exposure to Tysabri® (natalizumab).

25. Participants currently taking both budesonide and prednisone (or equivalent) simultaneously.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Biological:
• adalimumab
Prefilled syringe, 40 mg (loading dose then every other week dosing). 80 mg at Week 0, 40 mg at Week 2, and 40 mg every other week starting at Week 4.
• adalimumab
Prefilled syringe, 40 mg (loading dose then every other week dosing). 160 mg at Week 0, 80 mg at Week 2, and 40 mg every other week starting at Week 4.
• placebo
Placebo for 40 mg syringe. Matching placebo for loading dose and every other week dosing. Subjects received placebo at Weeks 0, 2, 4, and 6, followed by 160 mg adalimumab at Week 8, 80 mg adalimumab at Week 10, and 40 mg adalimumab eow thereafter (prior to Amendment 3) or 40 mg adalimumab eow starting at Week 8 (after Amendment 3).

Locations

Country	Name	City	State
Austria	Site Ref # / Investigator 4936	Graz
Austria	Site Ref # / Investigator 6224	Hall
Austria	Site Ref # / Investigator 3830	Innsbruck
Austria	Site Ref # / Investigator 7508	Linz
Austria	Site Ref # / Investigator 3829	Salzburg
Austria	Site Ref # / Investigator 3831	Vienna
Austria	Site Ref # / Investigator 4937	Vienna
Belgium	Site Ref # / Investigator 3861	Bonheiden
Belgium	Site Ref # / Investigator 3859	Liege
Belgium	Site Ref # / Investigator 3862	Roeselare
Canada	Site Ref # / Investigator 2224	Calgary	Alberta
Canada	Site Ref # / Investigator 2227	Edmonton	Alberta
Canada	Site Ref # / Investigator 2138	Toronto	Ontario
Canada	Site Ref # / Investigator 2226	Vancouver	British Columbia
Canada	Site Ref # / Investigator 2223	Winnipeg	Manitoba
Czech Republic	Site Ref # / Investigator 3858	Brno
Czech Republic	Site Ref # / Investigator 3856	Olomouc
Czech Republic	Site Ref # / Investigator 3857	Ostrava
Czech Republic	Site Ref # / Investigator 3854	Prague 1
Czech Republic	Site Ref # / Investigator 3855	Prague 7
Germany	Site Ref # / Investigator 3832	Berlin
Germany	Site Ref # / Investigator 13983	Essen
Germany	Site Ref # / Investigator 3834	Jena
Germany	Site Ref # / Investigator 3833	Kiel
Germany	Site Ref # / Investigator 3878	Mainz
Germany	Site Ref # / Investigator 3897	Munich
Hungary	Site Ref # / Investigator 3850	Budapest
Hungary	Site Ref # / Investigator 3852	Budapest
Hungary	Site Ref # / Investigator 3849	Gyor
Italy	Site Ref # / Investigator 3876	Bologna
Italy	Site Ref # / Investigator 3848	Milan
Italy	Site Ref # / Investigator 3845	Palermo
Italy	Site Ref # / Investigator 3846	Rome
Italy	Site Ref # / Investigator 6232	Rome
Netherlands	Site Ref # / Investigator 3873	Eindhoven
Netherlands	Site Ref # / Investigator 3875	Leiden
Poland	Site Ref # / Investigator 8061	Lodz
Poland	Site Ref # / Investigator 13804	Sopot
Poland	Site Ref # / Investigator 8055	Warsaw
Puerto Rico	Site Ref # / Investigator 2392	Ponce
Puerto Rico	Site Ref # / Investigator 2393	San Juan
Slovakia	Site Ref # / Investigator 3839	Banska Bystrica
Slovakia	Site Ref # / Investigator 3838	Bratislava
Slovakia	Site Ref # / Investigator 3841	Bratislava
Slovakia	Site Ref # / Investigator 3842	Nitra
Slovakia	Site Ref # / Investigator 14721	Presov
Slovakia	Site Ref # / Investigator 14521	Trencin
Slovakia	Site Ref # / Investigator 3840	Trnava
Sweden	Site Ref # / Investigator 8503	Gothenburg
Sweden	Site Ref # / Investigator 8504	Linkoping
Sweden	Site Ref # / Investigator 8502	Lund
United States	Site Ref # / Investigator 2231	Atlanta	Georgia
United States	Site Ref # / Investigator 5393	Atlanta	Georgia
United States	Site Ref # / Investigator 2229	Bellevue	Washington
United States	Site Ref # / Investigator 2080	Birmingham	Alabama
United States	Site Ref # / Investigator 1971	Boston	Massachusetts
United States	Site Ref # / Investigator 2245	Bridgeport	Connecticut
United States	Site Ref # / Investigator 2236	Cedar Knolls	New Jersey
United States	Site Ref # / Investigator 2241	Charlotte	North Carolina
United States	Site Ref # / Investigator 2078	Chevy Chase	Maryland
United States	Site Ref # / Investigator 2498	Chicago	Illinois
United States	Site Ref # / Investigator 2074	Cincinnati	Ohio
United States	Site Ref # / Investigator 2126	Cleveland	Ohio
United States	Site Ref # / Investigator 5100	Fayetteville	Arkansas
United States	Site Ref # / Investigator 2240	Gainesville	Florida
United States	Site Ref # / Investigator 6090	Germantown	Tennessee
United States	Site Ref # / Investigator 2243	Kansas City	Missouri
United States	Site Ref # / Investigator 2233	Lincoln	Nebraska
United States	Site Ref # / Investigator 2247	Mexico	Missouri
United States	Site Ref # / Investigator 2077	Milwaukee	Wisconsin
United States	Site Ref # / Investigator 6034	Mobile	Alabama
United States	Site Ref # / Investigator 2076	Nashville	Tennessee
United States	Site Ref # / Investigator 2072	New York	New York
United States	Site Ref # / Investigator 5390	Orange	California
United States	Site Ref # / Investigator 2232	Raleigh	North Carolina
United States	Site Ref # / Investigator 2246	Rochester	Minnesota
United States	Site Ref # / Investigator 5392	San Diego	California
United States	Site Ref # / Investigator 2238	Silver Springs	Maryland
United States	Site Ref # / Investigator 2230	South Miami	Florida
United States	Site Ref # / Investigator 11801	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Abbott

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Czech Republic,  Germany,  Hungary,  Italy,  Netherlands,  Poland,  Puerto Rico,  Slovakia,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants With Clinical Remission Per Mayo Score at Week 8	Clinical remission per Mayo score is defined as a total Mayo score <= 2 and no individual subscore > 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, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).	Week 8	No
Secondary	Ranked Secondary Endpoint #1: Proportion of Participants With Clinical Response Per Mayo Score at Week 8 (Adalimumab 160/80/40 Versus Placebo).	Clinical response per Mayo score is defined as a decrease in Mayo score of >= 3 points and >= 30% from Baseline, plus either a decrease in rectal bleeding subscore of >= 1 point or an absolute rectal bleeding subscore 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: Stool Frequency Subscore, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).	Week 8	No
Secondary	Ranked Secondary Endpoint #2: Proportion of Participants With Mucosal Healing at Week 8 (Adalimumab 160/80/40 Versus Placebo).	Mucosal healing is defined as 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	No
Secondary	Ranked Secondary Endpoint #3: Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).	Rectal Bleeding Subscore 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	No
Secondary	Ranked Secondary Endpoint #4: Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).	The Physician's Global Assessment Subscore acknowledges the 3 other subscores (Stool Frequency, Rectal Bleeding, and Endoscopy), the subject's daily record of abdominal discomfort and functional assessment, and other observations such as physical findings and the subject'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	No
Secondary	Ranked Secondary Endpoint #5: Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 160/80/40 Versus Placebo).	Stool Frequency Subscore 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	Week 8	No
Secondary	Ranked Secondary Endpoint #6: Proportion of Participants With Clinical Response Per Mayo Score at Week 8 (Adalimumab 80/40 Versus Placebo).	Clinical response per Mayo score is defined as a decrease in Mayo score of >= 3 points and >= 30% from Baseline, plus either a decrease in rectal bleeding subscore of >= 1 point or an absolute rectal bleeding subscore 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: Stool Frequency Subscore, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).	Week 8	No
Secondary	Ranked Secondary Endpoint #7: Proportion of Participants With Mucosal Healing at Week 8 (Adalimumab 80/40 Versus Placebo).	Mucosal healing defined as 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	No
Secondary	Ranked Secondary Endpoint #8: Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).	Rectal Bleeding Subscore 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	No
Secondary	Ranked Secondary Endpoint #9: Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).	The Physician's Global Assessment Subscore acknowledges the 3 other subscores (Stool Frequency, Rectal Bleeding, and Endoscopy), the subject's daily record of abdominal discomfort and functional assessment, and other observations such as physical findings and the subject'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	No
Secondary	Ranked Secondary Endpoint #10: Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 8 (Adalimumab 80/40 Versus Placebo).	Stool Frequency Subscore 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	Week 8	No
Secondary	Ranked Secondary Endpoint #11: Proportion of IBDQ Responders at Week 8 (Adalimumab 160/80/40 Versus Placebo).	Response per the Inflammatory Bowel Disease Questionnaire (IBDQ) defined as 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 each question 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	No
Secondary	Ranked Secondary Endpoint #12: Proportion of IBDQ Responders at Week 8 (Adalimumab 80/40 Versus Placebo).	Response per the Inflammatory Bowel Disease Questionnaire (IBDQ) defined as 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 each question 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	No
Secondary	Proportion of Participants With Clinical Remission Per Mayo Score at Week 52	Clinical remission per Mayo score is defined as a total Mayo score <= 2 and no individual subscore > 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, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).	Week 52	No
Secondary	Proportion of Participants With Clinical Remission Per Partial Mayo Score at Week 52	Clinical remission per partial Mayo score is defined as a partial Mayo score <= 2 and no individual subscore > 1.; The partial Mayo score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).	Week 52	No
Secondary	Proportion of Participants With Clinical Response Per Mayo Score at Week 52	Clinical response per Mayo score is defined as a decrease in Mayo score of >= 3 points and >= 30% from Baseline, plus either a decrease in rectal bleeding subscore of >= 1 point or an absolute rectal bleeding subscore 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: Stool Frequency Subscore, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).	Week 52	No
Secondary	Proportion of Participants With Clinical Response Per Partial Mayo Score at Week 52	Clinical response per partial Mayo score is defined as a decrease in partial Mayo score of >= 2 points and >= 30% from Baseline, plus either a decrease in rectal bleeding subscore of >= 1 point or an absolute rectal bleeding subscore of 0 or 1.; The partial Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).	Week 52	No
Secondary	Proportion of Participants With Mucosal Healing at Week 52	Mucosal healing is defined as 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	No
Secondary	Proportion of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (<= 1) at Week 52	Rectal Bleeding Subscore 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 52	No
Secondary	Proportion of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (<= 1) at Week 52	The Physician's Global Assessment Subscore acknowledges the 3 other subscores (Stool Frequency, Rectal Bleeding, and Endoscopy), the subject's daily record of abdominal discomfort and functional assessment, and other observations such as physical findings and the subject'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 52	No
Secondary	Proportion of Participants With Stool Frequency Subscore Indicative of Mild Disease (<= 1) at Week 52	Stool Frequency Subscore 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	Week 52	No
Secondary	Proportion of Participants With Clinical Remission Per Mayo Score at Week 52 Among Participants Who Were Systemic Corticosteroid-free at Week 52	Clinical remission per Mayo score is defined as a total Mayo score <= 2 and no individual subscore > 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, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).	Week 52	No