Clinical trial NCT01070303: Remission in Subjects With Crohn's Disease, Open Label Extension
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn's Disease
Keywords: HUMIRA
adalimumab
Inflammatory Bowel Disease
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2010-02-18
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: 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).
timeFrame: Week 104
Secondary outcomes:
measure: Number of Participants Achieving Clinical Remission (CDAI < 150 Points) at Week 152 (Through 2 Years of Participation in NCT01070303).
timeFrame: Week 152
measure: Number of Participants Achieving Clinical Remission (CDAI < 150 Points) at Week 212 (Through 3 Years of Participation in NCT01070303).
timeFrame: Week 212
measure: Number of Participants Achieving Clinical Remission (CDAI < 150 Points) at Week 260 (4 Years of Participation in NCT01070303).
timeFrame: Week 260
measure: Number of Participants Achieving CR-100 at Week 104 (1 Year of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 104
measure: Number of Participants Achieving CR-100 at Week 152 (2 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 152
measure: Number of Participants Achieving CR-100 at Week 212 (3 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 212
measure: Number of Participants Achieving CR-100 at Week 260 (4 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 260
measure: Number of Participants Achieving CR-70 at Week 104 (1 Year of Participation in NCT01070303)
timeFrame: Week 104
measure: Number of Participants Achieving CR-70 at Week 152 (2 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in Study to Week 152
measure: Number of Participants Achieving CR-70 at Week 212 (3 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 212
measure: Number of Participants Achieving CR-70 at Week 260 (4 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 260
measure: Number of Participants Achieving Steroid-free Clinical Remission at Week 104 (1 Year of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 104
measure: Number of Achieving Steroid-free Clinical Remission at Week 152 (2 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 152
measure: Number of Participants Achieving Steroid-free Clinical Remission at Week 212 (3 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 212
measure: Number of Participants Achieving Steroid-free Clinical Remission at Week 260 (4 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 260
measure: Number of Participants Achieving Steroid-free CR-100 at Week 104 (1 Year of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 104
measure: Number of Participants Achieving Steroid-free CR-100 at Week 152 (2 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 152
measure: Number of Participants Achieving Steroid-free CR-100 at Week 212 (3 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 212
measure: Number of Participants Achieving Steroid-free CR-100 at Week 260 (4 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 260
measure: Changes in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores
timeFrame: Change from Baseline of lead-in study at Weeks 104, 152, 200, and 248
measure: Number of Participants Achieving Fistula Remission at Week 104 (1 Year of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 104
measure: Number of Participants Achieving Fistula Remission at Week 152 (2 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 152
measure: Number of Participants Achieving Fistula Remission at Week 212 (3 Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 212
measure: Number of Participants Achieving Fistula Remission at Week 260 (Years of Participation in NCT01070303)
timeFrame: From Baseline of lead-in study to Week 260
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: Gastroenterology Associates of the East Bay
state: California
city: Long Beach
country: United States
facility: Long Beach Gastroenterology Assoc.
state: California
city: San Diego
country: United States
facility: Sharp Rees-Stealy Medical Group
state: California
city: Bridgeport
country: United States
facility: Gastroenterology Assoc. of Fairfield Co.
state: Connecticut
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Weston
country: United States
facility: Wake Research Associates
state: Florida
city: Winter Park
country: United States
facility: Shafran Gastroenterology Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Assoc.
state: Georgia
city: Savannah
country: United States
facility: Southeastern Digestive & Liver Disease
state: Georgia
city: Arlington Heights
country: United States
facility: Northwest Gastroenterologists, S.C.
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Metairie
country: United States
facility: Drug Research Services, Inc.
state: Louisiana
city: New Orleans
country: United States
facility: LSU School of Medicine
state: Louisiana
city: Annapolis
country: United States
facility: Digestive Disorders Associates
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Worchester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic and Mayo Foundation
state: Minnesota
city: Kansas City
country: United States
facility: Gastroenterology and Hepatology
state: Missouri
city: Mexico
country: United States
facility: Glenn Gordon, MD
state: Missouri
city: Billings
country: United States
facility: Deaconess Billings Clinic Research Division
state: Montana
city: Lincoln
country: United States
facility: Gastroenterology Specialties, P.C.
state: Nebraska
city: Great Neck
country: United States
facility: Long Island Clinical Research Associates
state: New York
city: Lake Success
country: United States
facility: NY Center for Clinical Research
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Daniel Present
state: New York
city: Rochester
country: United States
facility: Rochester Institute for Digestive Diseases
state: New York
city: Chapel Hill
country: United States
facility: UNC School of Medicine
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Gastroenterology and Hepatology
state: North Carolina
city: Charlotte
country: United States
facility: Carolina Research Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: Digestive Health Specialists
state: North Carolina
city: Cincinnati
country: United States
facility: Consultants for Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Foundation for Digestive Disease
state: Oklahoma
city: Tulsa
country: United States
facility: Research Solutions
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Peter Molloy, MD
state: Pennsylvania
city: Chattanooga
country: United States
facility: Diseases of the Digestive System
state: Tennessee
city: Nashville
country: United States
facility: Nashville Medical Research Institute
state: Tennessee
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
city: Bellevue
country: United States
facility: Northwest Gastroenterology
state: Washington
city: Spokane
country: United States
facility: Inland Empire Gastroenterology
state: Washington
city: Tacoma
country: United States
facility: Tacoma Digestive Disease Center
state: Washington
city: Milwaukee
country: United States
facility: Wisconsin Center for Advanced Research
state: Wisconsin
Study officials:
affiliation: Abbott
name: Anne Camez, MD
role: STUDY_DIRECTOR
References:
citation: 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.