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

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

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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Biological: Adalimumab 40 mg eow or ew

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Berkeley, California, United States, 94705
      • Gastroenterology Associates of the East Bay
    • Long Beach, California, United States, 90806
      • Long Beach Gastroenterology Assoc.
    • San Diego, California, United States, 92123
      • Sharp Rees-Stealy Medical Group
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Gastroenterology Assoc. of Fairfield Co.
  • Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
    • Weston, Florida, United States, 33331
      • Wake Research Associates
    • Winter Park, Florida, United States, 32789
      • Shafran Gastroenterology Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Atlanta Gastroenterology Assoc.
    • Savannah, Georgia, United States, 31404
      • Southeastern Digestive & Liver Disease
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Gastroenterologists, S.C.
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Louisiana
    • Metairie, Louisiana, United States, 70001
      • Drug Research Services, Inc.
    • New Orleans, Louisiana, United States, 70115
      • LSU School of Medicine
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Digestive Disorders Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Worchester, Massachusetts, United States, 01610
      • Clinical Pharmacology Study Group
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic and Mayo Foundation
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Gastroenterology and Hepatology
    • Mexico, Missouri, United States, 65265
      • Glenn Gordon, MD
  • Montana
    • Billings, Montana, United States, 59101
      • Deaconess Billings Clinic Research Division
  • Nebraska
    • Lincoln, Nebraska, United States, 68503
      • Gastroenterology Specialties, P.C.
  • New York
    • Great Neck, New York, United States, 11021
      • Long Island Clinical Research Associates
    • Lake Success, New York, United States, 11042
      • NY Center for Clinical Research
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital
    • New York, New York, United States, 10029
      • Daniel Present
    • Rochester, New York, United States, 14607
      • Rochester Institute for Digestive Diseases
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC School of Medicine
    • Charlotte, North Carolina, United States, 28262
      • Carolina Research Associates
    • Charlotte, North Carolina, United States, 28207
      • Charlotte Gastroenterology and Hepatology
    • Winston-Salem, North Carolina, United States, 27103
      • Digestive Health Specialists
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Consultants for Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Foundation for Digestive Disease
    • Tulsa, Oklahoma, United States, 74104
      • Research Solutions
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
    • Pittsburgh, Pennsylvania, United States, 15224
      • Peter Molloy, MD
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Diseases of the Digestive System
    • Nashville, Tennessee, United States, 37205
      • Nashville Medical Research Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • Charlottesville Medical Research
  • Washington
    • Bellevue, Washington, United States, 98004
      • Northwest Gastroenterology
    • Spokane, Washington, United States, 99204
      • Inland Empire Gastroenterology
    • Tacoma, Washington, United States, 98405
      • Tacoma Digestive Disease Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53207
      • Wisconsin Center for Advanced Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adalimumab 40 mg every other week or every week	Biological: Adalimumab 40 mg eow or ew; Adalimumab 40 mg by subcutaneous injection every other week or every week; Other Names: Humira; Adalimumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Anne Camez, MD, Abbott

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2002
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: February 16, 2010
• First Submitted That Met QC Criteria: February 16, 2010
• First Posted (Estimate): February 18, 2010

Study Record Updates

• Last Update Posted (Estimate): April 11, 2011
• Last Update Submitted That Met QC Criteria: April 7, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Inflammatory Bowel Disease; adalimumab; HUMIRA
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: M02-433 Open Label