Remission in Subjects With Crohn's Disease, Open Label Extension

Crohn's Disease Clinical Trial

— CLASSICII  

Official title:

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, Open Label Extension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01070303
• Other study ID #: M02-433 Open Label
• Status: Completed
• Phase: Phase 3
• First received: February 16, 2010
• Last updated: April 7, 2011
• Start date: August 2002
• Est. completion date: December 2008

Study information

• Verified date: April 2011
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objectives were: (1) To demonstrate the efficacy of adalimumab in the long-term maintenance of clinical remission in participants with Crohn's disease; and (2) To delineate the long-term safety of adalimumab when administered to participants with Crohn's disease.

Description:

Study M02-433 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. a 1-year phase (Week 0 to Week 56) (NCT00055497) that consisted of a randomized, double-blind, placebo-controlled portion with a concomitant open label (OL) portion, and 2. a long-term open-label extension (OLE) phase (NCT01070303) that lasted 264 additional weeks (Week 56 to Week 320).

Participants who completed the lead-in study NCT00055523, were eligible to participate in the rollover study, NCT00055497. 176 participants were documented as having completed Year 1 (NCT00055497); however, 177 participants were still receiving study drug and were evaluated at Week 56 of NCT00055497; these participants are included in the OLE data (NCT01070303).

At Week 4 of NCT00055497, participants who demonstrated clinical remission (defined as a Crohn's Disease Activity Index [CDAI] score <150 points) at Baseline of NCT00055497 and who remained in clinical remission at Week 4 ("Remitters") were randomized to receive 1 of 3 blinded treatments: placebo, adalimumab 40 mg every other week (eow), or adalimumab 40 mg every week (ew). Participants who did not demonstrate clinical remission at Baseline of NCT00055497 or who were no longer in clinical remission at Week 4 of NCT00055497 ("Non-remitters") were assigned to receive OL adalimumab 40 mg eow. All study drug (placebo and active) was administered by subcutaneous (SC) injection.

At any time during Study NCT00055497, a participant receiving blinded study drug who developed a disease flare could be switched to OL adalimumab 40 mg eow. A participant receiving OL adalimumab 40 mg SC eow who developed a flare or was a non-responders could have had his/her dose increased to 40 mg SC ew.

After 1 year (Week 56 of NCT00055497), patients who were still participating could continue in the OLE phase (NCT01070303). Participants who were receiving blinded study drug were switched to OL adalimumab 40 mg SC eow, and participants who were receiving OL study drug continued on their previous OL adalimumab dose (adalimumab 40 mg SC eow or ew).

Data are summarized for Remitters and Non-remitters, with the exception of data for primary reason for noncompletion. Summaries of primary reason for noncompletion were available only for all participants, not for Remitters and Non-remitters. Data are reported for Weeks 104, 152, 212, and 260 of Study M02-433, starting from Week 0 of NCT00055497; these weeks correspond to 1, 2, 3, and 4 years of participation in NCT01070303. Change from Baseline results (clinical response 70, clinical response 100, Inflammatory Bowel Disease Questionnaire, and fistula remission) are calculated from Baseline of the lead-in study (NCT00055523). Results on each assessment at each measurement time point are presented as individual outcome measures because different numbers of participants were evaluated at each time point (as observed analysis).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 177
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Participant had completed the Year 1 of Study M02-433 (NCT00055497)

• Diagnosis of Crohn's disease

• Willing and able to give informed consent

Exclusion Criteria:

• Diagnosis of ulcerative colitis

• Pregnancy or breastfeeding

• Previous use of infliximab or other anti-TNF (tumor necrosing factor) antagonists

• Previous history of active tuberculosis or listeria infection

• Previous history of cancer other than successfully treated skin cancer

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Biological:
• Adalimumab 40 mg eow or ew
Adalimumab 40 mg by subcutaneous injection every other week or every week

Locations

Country	Name	City	State
United States	Digestive Disorders Associates	Annapolis	Maryland
United States	Northwest Gastroenterologists, S.C.	Arlington Heights	Illinois
United States	Atlanta Gastroenterology Assoc.	Atlanta	Georgia
United States	Northwest Gastroenterology	Bellevue	Washington
United States	Gastroenterology Associates of the East Bay	Berkeley	California
United States	Deaconess Billings Clinic Research Division	Billings	Montana
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Gastroenterology Assoc. of Fairfield Co.	Bridgeport	Connecticut
United States	UNC School of Medicine	Chapel Hill	North Carolina
United States	Carolina Research Associates	Charlotte	North Carolina
United States	Charlotte Gastroenterology and Hepatology	Charlotte	North Carolina
United States	Charlottesville Medical Research	Charlottesville	Virginia
United States	Diseases of the Digestive System	Chattanooga	Tennessee
United States	University of Chicago	Chicago	Illinois
United States	Consultants for Clinical Research	Cincinnati	Ohio
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Long Island Clinical Research Associates	Great Neck	New York
United States	Gastroenterology and Hepatology	Kansas City	Missouri
United States	NY Center for Clinical Research	Lake Success	New York
United States	Gastroenterology Specialties, P.C.	Lincoln	Nebraska
United States	Long Beach Gastroenterology Assoc.	Long Beach	California
United States	Drug Research Services, Inc.	Metairie	Louisiana
United States	Glenn Gordon, MD	Mexico	Missouri
United States	Wisconsin Center for Advanced Research	Milwaukee	Wisconsin
United States	Nashville Medical Research Institute	Nashville	Tennessee
United States	LSU School of Medicine	New Orleans	Louisiana
United States	Daniel Present	New York	New York
United States	New York Presbyterian Hospital	New York	New York
United States	Oklahoma Foundation for Digestive Disease	Oklahoma City	Oklahoma
United States	Peter Molloy, MD	Pittsburgh	Pennsylvania
United States	Mayo Clinic and Mayo Foundation	Rochester	Minnesota
United States	Rochester Institute for Digestive Diseases	Rochester	New York
United States	Sharp Rees-Stealy Medical Group	San Diego	California
United States	Southeastern Digestive & Liver Disease	Savannah	Georgia
United States	Inland Empire Gastroenterology	Spokane	Washington
United States	Tacoma Digestive Disease Center	Tacoma	Washington
United States	Research Solutions	Tulsa	Oklahoma
United States	Cleveland Clinic Florida	Weston	Florida
United States	Wake Research Associates	Weston	Florida
United States	Digestive Health Specialists	Winston-Salem	North Carolina
United States	Shafran Gastroenterology Center	Winter Park	Florida
United States	Clinical Pharmacology Study Group	Worchester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Abbott

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Achieving Clinical Remission (Crohn's Disease Activity Index[CDAI] <150 Points) at Week 104 of Study M02-433 (Starting From Week 0 of NCT00055497) (Through 1 Year of Participation in NCT01070303).	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 NCT01070303 was 0 to 464. A lower score indicates less severe Crohn's disease activity.	Week 104	No
Secondary	Number of Participants Achieving Clinical Remission (CDAI < 150 Points) at Week 152 (Through 2 Years of Participation in NCT01070303).	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 NCT01070303 was 0 to 464. A lower score indicates less severe Crohn's disease activity.	Week 152	No
Secondary	Number of Participants Achieving Clinical Remission (CDAI < 150 Points) at Week 212 (Through 3 Years of Participation in NCT01070303).	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 NCT01070303 was 0 to 464. A lower score indicates less severe Crohn's disease activity.	Week 212	No
Secondary	Number of Participants Achieving Clinical Remission (CDAI < 150 Points) at Week 260 (4 Years of Participation in NCT01070303).	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 NCT01070303 was 0 to 464. A lower score indicates less severe Crohn's disease activity.	Week 260	No
Secondary	Number of Participants Achieving CR-100 at Week 104 (1 Year of Participation in NCT01070303)	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 NCT01070303 was 0 to 464. Scores at Baseline of the lead-in study (NCT00055523), which were used to calculate clinical response, ranged from 201 to 450. A lower score indicates less severe Crohn's disease activity.	From Baseline of lead-in study to Week 104	No
Secondary	Number of Participants Achieving CR-100 at Week 152 (2 Years of Participation in NCT01070303)	A CR-100 is a decrease from Baseline of lead-in study (NCT00055523) in CDAI score of 100 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 NCT01070303 was 0 to 464. Scores at Baseline of the lead-in study (NCT00055523), which were used to calculate clinical response, ranged from 201 to 450. A lower score indicates less severe Crohn's disease activity.	From Baseline of lead-in study to Week 152	No
Secondary	Number of Participants Achieving CR-100 at Week 212 (3 Years of Participation in NCT01070303)	A CR-100 is a decrease from Baseline of lead-in study (NCT00055523) in CDAI score of 100 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 NCT01070303 was 0 to 464. Scores at Baseline of the lead-in study (NCT00055523), which were used to calculate clinical response, ranged from 201 to 450. A lower score indicates less severe Crohn's disease activity.	From Baseline of lead-in study to Week 212	No
Secondary	Number of Participants Achieving CR-100 at Week 260 (4 Years of Participation in NCT01070303)	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 NCT01070303 was 0 to 464. Scores at Baseline of the lead-in study (NCT00055523), which were used to calculate clinical response, ranged from 201 to 450. A lower score indicates less severe Crohn's disease activity.	From Baseline of lead-in study to Week 260	No
Secondary	Number of Participants Achieving CR-70 at Week 104 (1 Year of Participation in NCT01070303)	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 NCT01070303 was 0 to 464. Scores at Baseline of the lead-in study (NCT00055523), which were used to calculate clinical response, ranged from 201 to 450. A lower score indicates less severe Crohn's disease activity.	Week 104	No
Secondary	Number of Participants Achieving CR-70 at Week 152 (2 Years of Participation in NCT01070303)	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 NCT01070303 was 0 to 464. Scores at Baseline of the lead-in study (NCT00055523), which were used to calculate clinical response, ranged from 201 to 450. A lower score indicates less severe Crohn's disease activity.	From Baseline of lead-in Study to Week 152	No
Secondary	Number of Participants Achieving CR-70 at Week 212 (3 Years of Participation in NCT01070303)	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 NCT01070303 was 0 to 464. Scores at Baseline of the lead-in study (NCT00055523), which were used to calculate clinical response, ranged from 201 to 450. A lower score indicates less severe Crohn's disease activity.	From Baseline of lead-in study to Week 212	No
Secondary	Number of Participants Achieving CR-70 at Week 260 (4 Years of Participation in NCT01070303)	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 NCT01070303 was 0 to 464. Scores at Baseline of the lead-in study (NCT00055523), which were used to calculate clinical response, ranged from 201 to 450. A lower score indicates less severe Crohn's disease activity.	From Baseline of lead-in study to Week 260	No
Secondary	Number of Participants Achieving Steroid-free Clinical Remission at Week 104 (1 Year of Participation in NCT01070303)	Among participants who were taking systemic corticosteroids at Baseline of the lead-in study (NCT00055523), steroid-free remission was achieved if the participant stopped taking corticosteroids before the visit and had a CDAI score < 150 points at that visit.	From Baseline of lead-in study to Week 104	No
Secondary	Number of Achieving Steroid-free Clinical Remission at Week 152 (2 Years of Participation in NCT01070303)	Among participants who were taking systemic corticosteroids at Baseline of the lead-in study (NCT00055523), steroid-free remission was achieved if the participant stopped taking corticosteroids before the visit and had a CDAI score < 150 points at that visit.	From Baseline of lead-in study to Week 152	No
Secondary	Number of Participants Achieving Steroid-free Clinical Remission at Week 212 (3 Years of Participation in NCT01070303)	Among participants who were taking systemic corticosteroids at Baseline of the lead-in study (NCT00055523), steroid-free remission was achieved if the participant stopped taking corticosteroids before the visit and had a CDAI score < 150 points at that visit.	From Baseline of lead-in study to Week 212	No
Secondary	Number of Participants Achieving Steroid-free Clinical Remission at Week 260 (4 Years of Participation in NCT01070303)	Among participants who were taking systemic corticosteroids at Baseline of the lead-in study (NCT00055523), steroid-free remission was achieved if the participant stopped taking corticosteroids before the visit and had a CDAI score < 150 points at that visit.	From Baseline of lead-in study to Week 260	No
Secondary	Number of Participants Achieving Steroid-free CR-100 at Week 104 (1 Year of Participation in NCT01070303)	Among participants who were taking systemic corticosteroids at Baseline of the lead-in study (NCT00055523), steroid-free CR-100 was achieved if the participant stopped taking steroids before the visit and had a decrease from Baseline in CDAI score of 100 or more points at that visit.	From Baseline of lead-in study to Week 104	No
Secondary	Number of Participants Achieving Steroid-free CR-100 at Week 152 (2 Years of Participation in NCT01070303)	Among participants who were taking systemic corticosteroids at Baseline of the lead-in study (NCT00055523), steroid-free CR-100 was achieved if the participant stopped taking steroids before the visit and had a decrease from Baseline in CDAI score of 100 or more points at that visit.	From Baseline of lead-in study to Week 152	No
Secondary	Number of Participants Achieving Steroid-free CR-100 at Week 212 (3 Years of Participation in NCT01070303)	Among participants who were taking systemic corticosteroids at Baseline of the lead-in study (NCT00055523), steroid-free CR-100 was achieved if the participant stopped taking steroids before the visit and had a decrease from Baseline in CDAI score of 100 or more points at that visit.	From Baseline of lead-in study to Week 212	No
Secondary	Number of Participants Achieving Steroid-free CR-100 at Week 260 (4 Years of Participation in NCT01070303)	Among participants who were taking systemic corticosteroids at Baseline of the lead-in study (NCT00055523), steroid-free CR-100 was achieved if the participant stopped taking steroids before the visit and had a decrease from Baseline in CDAI score of 100 or more points at that visit.	From Baseline of lead-in study to Week 260	No
Secondary	Changes in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores	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 at Weeks 104, 152, 200, and 248	No
Secondary	Number of Participants Achieving Fistula Remission at Week 104 (1 Year of Participation in NCT01070303)	A count of the number of cutaneous fistulas draining upon gentle compression was performed at Baseline of the lead-in study (NCT00055523) and at study visits. Among participants with draining fistulas at Baseline of NCT00055523, a participant was considered to have achieved fistula remission at a study visit if the participant had no draining cutaneous fistulas at that visit.	From Baseline of lead-in study to Week 104	No
Secondary	Number of Participants Achieving Fistula Remission at Week 152 (2 Years of Participation in NCT01070303)	A count of the number of cutaneous fistulas draining upon gentle compression was performed at Baseline of the lead-in study (NCT00055523) and at study visits. Among participants with draining fistulas at Baseline of NCT00055523, a participant was considered to have achieved fistula remission at a study visit if the participant had no draining cutaneous fistulas at that visit.	From Baseline of lead-in study to Week 152	No
Secondary	Number of Participants Achieving Fistula Remission at Week 212 (3 Years of Participation in NCT01070303)	A count of the number of cutaneous fistulas draining upon gentle compression was performed at Baseline of the lead-in study (NCT00055523) and at study visits. Among participants with draining fistulas at Baseline of NCT00055523, a participant was considered to have achieved fistula remission at a study visit if the participant had no draining cutaneous fistulas at that visit.	From Baseline of lead-in study to Week 212	No
Secondary	Number of Participants Achieving Fistula Remission at Week 260 (Years of Participation in NCT01070303)	A count of the number of cutaneous fistulas draining upon gentle compression was performed at Baseline of the lead-in study (NCT00055523) and at study visits. Among participants with draining fistulas at Baseline of NCT00055523, a participant was considered to have achieved fistula remission at a study visit if the participant had no draining cutaneous fistulas at that visit.	From Baseline of lead-in study to Week 260	No