Remission in Subjects With Crohn's Disease, 1 Year Phase

Study Overview
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Brief Summary
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The objectives were: (1) To demonstrate the efficacy of adalimumab in the maintenance of clinical remission up to 56 weeks in participants with Crohn's disease who participated in NCT00055523; (2) To delineate the safety of adalimumab when administered to participants with Crohn's disease up to 56 weeks.

Detailed Description
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Study NCT00055497 was designed to evaluate the efficacy and safety of adalimumab in the maintenance of clinical remission in patients with Crohn's disease (CD). The study consisted of 2 phases: 1. the first year phase lasting until Week 56 and consisting of a randomized, double-blind (DB), placebo-controlled portion (NCT00055497) and of a concomitant open label (OL) portion, and 2. a long-term extension phase (NCT01070303) that lasted 264 additional weeks (Week 56 to Week 320). Potential participants were screened at the time of enrollment in the lead-in, induction therapy study (NCT00055523). Participants who completed the lead-in study, NCT00055523, were eligible to participate in the rollover study, NCT00055497. In Study NCT00055497, all participants received 40 mg of adalimumab subcutaneously (SC) at Baseline (Week 0) and Week 2 of Study NCT00055497. Baseline of Study NCT00055497 is synonymous with NCT00055523 Week 4. At Week 4 of Study NCT00055497, participants were randomized based on their clinical remission status at Baseline and Week 4 of Study NCT00055497. Participants who demonstrated clinical remission (defined as a Crohn's Disease Activity Index [CDAI] score < 150 points) at Baseline of Study NCT00055497 and who remained in clinical remission at Week 4 of Study NCT00055497 (those participants constituted the randomized analysis set) were randomized to receive 1 of 3 blinded treatments: adalimumab 40 mg every other week (eow), adalimumab 40 mg every week (ew), or placebo. Participants who did not demonstrate clinical remission at Baseline of Study NCT00055497, or who were no longer in clinical remission at Week 4 of Study NCT00055497 were assigned to receive OL adalimumab 40 mg eow; those participants constituted the OL analysis set. At any time during Study NCT00055497, participants receiving OL adalimumab 40 mg SC eow who developed a flare or were non-responders during OL treatment could have had his/her dose increased to 40 mg SC weekly. Participants who were documented as having completed Week 56 are counted in the study completion total. After 1 year (Week 56), participants who met eligibility criteria for the long-term extension phase (NCT01070303) were switched to OL adalimumab 40 mg subcutaneous (SC) eow, and participants previously in the OL treatment group of Study NCT00055497 continued on their previous OL adalimumab dose (adalimumab 40 mg SC eow or every week).

Official Title
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A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Maintenance of Clinical Remission in Subjects With Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Biological: Double-blind (DB) adalimumab placebo
* Biological: DB adalimumab 40 mg eow
* Biological: DB adalimumab 40 mg ew
* Biological: OL adalimumab 40 mg


Participation Criteria
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Eligibility Criteria
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Inclusion: Patient must have successfully completed the induction study NCT00055523 Diagnosis of Crohn's disease Willing and able to give informed consent Exclusion: Diagnosis of ulcerative colitis Pregnancy or breastfeeding Previous use of infliximab or other anti-TNF antagonists Previous history of active tuberculosis or listeria infection Previous history of cancer other than successfully treated skin cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Double-blind (DB) adalimumab placebo<br>Double-blind nonactive matching subcutaneous injection | Biological: Double-blind (DB) adalimumab placebo<br>* Double-blind nonactive matching subcutaneous injection<br>* Other names: Humira®;|
| Experimental: Double-blind adalimumab 40 mg every other week (eow)<br>Double-blind adalimumab 40 mg eow by subcutaneous injection | Biological: DB adalimumab 40 mg eow<br>* Double-blind adalimumab 40 mg every other week by subcutaneous injection<br>* Other names: Humira®;|
| Experimental: Double-blind adalimumab 40 mg every week (ew)<br>Double-blind adalimumab 40 mg every week by subcutaneous injection | Biological: DB adalimumab 40 mg ew<br>* Double-blind adalimumab 40 mg every week by subcutaneous injection<br>* Other names: Humira®;|
| Experimental: Open-label adalimumab 40 mg<br>Open-label adalimumab 40 mg eow or ew by subcutaneous injection | Biological: OL adalimumab 40 mg<br>* Open-label adalimumab every other week or every week by subcutaneous injection<br>* Other names: Humira®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Randomized Participants Achieving Clinical Remission at Week 56 - Non-Responder Imputation (NRI) | Clinical remission is defined as CDAI score <150. CDAI evaluates 8 Crohn's-related variables during a 1-week assessment period, yielding a composite score >/= 0 and without upper limit. The range of scores during Study NCT00055497 and the lead-in study (NCT00055523) was 0 to 633. A lower score indicates less severe Crohn's disease activity. | Week 56 | 
| Number of Randomized Participants Achieving Clinical Remission at Week 56 - Last Observation Carried Forward (LOCF) | Clinical remission is defined as CDAI score <150. CDAI evaluates 8 Crohn's-related variables during a 1-week assessment period, yielding a composite score >/= 0 and without upper limit. The range of scores during Study NCT00055497 and the lead-in study (NCT00055523) was 0 to 633. A lower score indicates less severe Crohn's disease activity. | Week 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving Clinical Remission at Week 24 - NRI | Clinical remission is defined as CDAI score <150. CDAI evaluates 8 Crohn's-related variables during a 1-week assessment period, yielding a composite score >/= 0 and without upper limit. The range of scores during Study NCT00055497 and the lead-in study (NCT00055523) was 0 to 633. A lower score indicates less severe Crohn's disease activity. | Week 24 | 
| Number of OL Participants Achieving Clinical Remission at Week 56 - NRI | Clinical remission is defined as CDAI score <150. CDAI evaluates 8 Crohn's-related variables during a 1-week assessment period, yielding a composite score >/= 0 and without upper limit. The range of scores during Study NCT00055497 and the lead-in study (NCT00055523) was 0 to 633. A lower score indicates less severe Crohn's disease activity. | Week 56 | 
| Number of Participants Achieving Clinical Response 100 (CR-100) - NRI | A CR-100 is a decrease from Baseline of lead-in study (NCT00055523) in CDAI score of 100 or more points, indicating significant improvement in disease severity. CDAI evaluates 8 Crohn's-related variables during a 1-week assessment period, yielding a composite score >/= 0 and without upper limit. The range of scores during Study NCT00055497 and the lead-in study (NCT00055523) was 0 to 633. A lower score indicates less severe Crohn's disease activity. | From Baseline of lead-in study to Week 24 and Week 56 | 
| Number of Participants Achieving Clinical Response 70 (CR-70)- NRI | A CR-70 is a decrease from Baseline of lead-in study (NCT00055523) in CDAI score of 70 or more points, indicating a significant improvement in disease severity. CDAI evaluates 8 Crohn's-related variables during a 1-week assessment period, yielding a composite score >/= 0 and without upper limit. The range of scores during Study NCT00055497 and the lead-in study (NCT00055523) was 0 to 633. A lower score indicates less severe Crohn's disease activity. | From Baseline of lead-in study to Week 24 and to Week 56 | 
| Number of Participants Achieving Clinical Remission at Week 24 - LOCF | Clinical remission is defined as CDAI score <150. CDAI evaluates 8 Crohn's-related variables during a 1-week assessment period, yielding a composite score >/= 0 and without upper limit. The range of scores during Study NCT00055497 and the lead-in study (NCT00055523) was 0 to 633. A lower score indicates less severe Crohn's disease activity. | Week 24 | 
| Number of OL Participants Achieving Clinical Remission at Week 56 - LOCF | Clinical remission is defined as CDAI score <150. CDAI evaluates 8 Crohn's-related variables during a 1-week assessment period, yielding a composite score >/= 0 and without upper limit. The range of scores during Study NCT00055497 and the lead-in study (NCT00055523) was 0 to 633. A lower score indicates less severe Crohn's disease activity. | Week 56 | 
| Number of Participants Achieving CR-100 - LOCF | A CR-100 is a decrease from Baseline of lead-in study (NCT00055523) in CDAI score of 100 or more points, indicating significant improvement in disease severity. CDAI evaluates 8 Crohn's-related variables during a 1-week assessment period, yielding a composite score >/= 0 and without upper limit. The range of scores during Study NCT00055497 and the lead-in study (NCT00055523) was 0 to 633. A lower score indicates less severe Crohn's disease activity. | From Baseline of lead-in study to Week 24 and Week 56 | 
| Number of Participants Achieving CR-70 - LOCF | A CR-70 is a decrease from Baseline of lead-in study (NCT00055523) in CDAI score of 70 or more points, indicating a significant improvement in disease severity. CDAI evaluates 8 Crohn's-related variables during a 1-week assessment period, yielding a composite score >/= 0 and without upper limit. The range of scores during Study NCT00055497 and the lead-in study (NCT00055523) was 0 to 633. A lower score indicates less severe Crohn's disease activity. | From Baseline of lead-in study to Week 24 and Week 56 | 
| Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores - LOCF | IBDQ is a validated disease-specific instrument that assesses the impact of IBD on patient quality of life during a 2-week recall period. It has 32 questions about bowel function and related symptoms, and their social and emotional impact. For each question, participants selected 1 of 7 responses, where 1=poor quality of life (e.g., feeling of fatigue all of the time) and 7=good quality on the item (e.g., feeling of fatigue none of the time). IBDQ scores range from 32 to 224. Higher scores indicate better quality of life, and increases in IBDQ indicate improved overall quality of life. | Change from Baseline of lead-in study to Week 24 and Week 56 |