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

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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Biological: Double-blind (DB) adalimumab placebo; Biological: DB adalimumab 40 mg eow; Biological: DB adalimumab 40 mg ew; Biological: OL adalimumab 40 mg

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 276
• 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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

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.
• Steenholdt C, Al-khalaf M, Brynskov J, Bendtzen K, Thomsen OO, Ainsworth MA. Clinical implications of variations in anti-infliximab antibody levels in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2012 Dec;18(12):2209-17. doi: 10.1002/ibd.22910. Epub 2012 Feb 16.

Study record dates

Study Major Dates

• Study Start: August 1, 2002
• Primary Completion (Actual): January 1, 2005
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: March 3, 2003
• First Submitted That Met QC Criteria: March 4, 2003
• First Posted (Estimate): March 5, 2003

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

• 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