Clinical trial NCT00445432: A Study of Adalimumab for the Maintenance of Clinical Remission in Japanese Subjects With Crohn's Disease
Official title: A Multi-Center, Randomized, Double-blind, Placebo-controlled Study of Adalimumab for the Maintenance of Clinical Remission in Japanese Subjects With Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Crohn's Disease
Lead sponsor: Abbott
Sponsor class: INDUSTRY
Collaborators: name: Eisai Co., Ltd.
First posted: 2007-03-09
Enrollment: 82
Sex: ALL
Minimum age (years): 15
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To demonstrate the efficacy and safety of adalimumab for the maintenance of clinical remission in Japanese subjects with Crohn's disease.

Detailed description: This was a Phase 2/3, multicenter, randomized, double-blind (DB), placebo-controlled, two-arm, efficacy, safety, and pharmacokinetic study designed to demonstrate the effectiveness of adalimumab in Japanese patients with moderate to severe Crohn's Disease (CD).

All participants who had completed Study M04-729 (NCT00445939), the lead-in adalimumab induction therapy study, were eligible for this study. Participants who rolled over into this study received either DB treatment (adalimumab or placebo) or open-label (OL) treatment with adalimumab.

Crohn's Disease Activity Index (CDAI) was used to determine participants who were responders and participants who were in clinical remission. CDAI documents number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss during a 1-week assessment period. It yields a total score \>= 0 and without upper limit. Baseline scores in the study ranged from 221 to 448. Low score=less severe CD activity. Decrease in score indicates improvement.

Clinical remission is a CDAI score \< 150.

Clinical response-70 (CR-70) = decrease in CDAI ≥ 70 points from lead-in study Baseline score.

Clinical response-100 (CR-100) = decrease in CDAI ≥ 100 points from lead-in study Baseline score.

Participants who had CR-70 response at Week 4 of the induction study were randomized into 1 of 2 treatment groups (double-blind adalimumab 40 mg every other week or adalimumab placebo every other week) using 2 stratification factors - CDAI category (CDAI less than 150 and CDAI 150 or higher) and presence/absence of fistula at Week 0 of this study. The double-blind treatment was to last from Week 0 to Week 52. Any time at or after Week 4 of this study, if a participant's disease flared (defined as a recurrence of very active disease, specifically an increase in CDAI when compared to Week 0 in this study of ≥ 70 points and a CDAI above 220) during the double-blind treatment period, the participant was allowed to move to OL treatment. At Week 52, all participants still receiving DB treatment were to be moved to open-label treatment and could continue in the study until adalimumab is approved for commercial use in Japan.

Participants who did not respond by Week 4 in the induction study and participants who had disease flare during DB treatment of this study entered OL treatment and received adalimumab 40 mg every other week. At or after Week 4 of this study, if a participant in the open-label treatment group had a disease flare or if the participant was still not responding to treatment, the participant was allowed to dose escalate to adalimumab 80 mg every other week. Participants who entered open-label treatment were to be allowed to continue on open-label adalimumab until adalimumab is approved for commercial use in Japan.

The study is complete. Results of this study are reported for endpoints at Week 52 (end of the DB treatment period) for subjects who received DB treatment (adalimumab or placebo) or OL adalimumab treatment and for endpoints at Week 148 for all subjects who received at least one dose of adalimumab in this study.

Eligibility criteria: Inclusion Criteria:

* Subjects who successfully enrolled in and completed the M04-729, (NCT00445939) study

Exclusion Criteria:

* Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study

Primary outcomes:
measure: Number of Participants Who Had Clinical Remission at Week 52 of Double-blind Treatment
timeFrame: Week 52 of double-blind treatment
Secondary outcomes:
measure: Number of Participants Who Had Clinical Response-70 (CR-70; a Decrease in Crohn's Disease Activity Index of at Least 70 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment
timeFrame: Week 52 of double-blind treatment
measure: Number of Participants Who Had Clinical Response-100 (CR-100; a Decrease in Crohn's Disease Activity Index of at Least 100 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment
timeFrame: Week 52 of double-blind treatment
measure: Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment
timeFrame: Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment
measure: Number of Participants Who Had Clinical Remission at Week 52 of Open-label Treatment
timeFrame: Week 52 of open-label treatment
measure: Change in International Organization for the Study of Inflammatory Bowel Disease (IOIBD) Score From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment
timeFrame: Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment
measure: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment
timeFrame: Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment
measure: Change in Physical Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment
timeFrame: Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment
measure: Change in Mental Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment
timeFrame: Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment
Other outcomes:
measure: Number of Participants Who Had Clinical Remission at Week 148
timeFrame: Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
measure: Number of Participants Who Had Clinical Response-70 (CR-70; a Decrease in Crohn's Disease Activity Index of at Least 70 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 148
timeFrame: Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
measure: Number of Participants Who Had Clinical Response-100 (CR-100; a Decrease in Crohn's Disease Activity Index of at Least 100 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 148
timeFrame: Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
measure: Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 148
timeFrame: Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
measure: Change in International Organization for the Study of Inflammatory Bowel Disease (IOIBD) Score From Baseline of Lead-in Study (NCT00445939) to Week 148
timeFrame: Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
measure: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) From Baseline of Lead-in Study (NCT00445939) to Week 148
timeFrame: Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
measure: Change in Physical Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 148
timeFrame: Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
measure: Change in Mental Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 148
timeFrame: Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
Locations:
city: Aichi
country: Japan
facility: Site Ref # / Investigator 46965
city: Aichi
country: Japan
facility: Site Ref # / Investigator 46977
city: Aichi
country: Japan
facility: Site Ref # / Investigator 46978
city: Aichi
country: Japan
facility: Site Ref # / Investigator 46979
city: Chiba
country: Japan
facility: Site Ref # / Investigator 46922
city: Chiba
country: Japan
facility: Site Ref # / Investigator 46974
city: Ehime
country: Japan
facility: Site Ref # / Investigator 46970
city: Fukuoka
country: Japan
facility: Site Ref # / Investigator 46971
city: Fukuoka
country: Japan
facility: Site Ref # / Investigator 46985
city: Fukuoka
country: Japan
facility: Site Ref # / Investigator 46986
city: Fukuoka
country: Japan
facility: Site Ref # / Investigator 46987
city: Hiroshima
country: Japan
facility: Site Ref # / Investigator 46968
city: Hokkaido
country: Japan
facility: Site Ref # / Investigator 46973
city: Hokkaido
country: Japan
facility: Site Ref # / Investigator 6881
city: Hyogo
country: Japan
facility: Site Ref # / Investigator 46982
city: Kagawa
country: Japan
facility: Site Ref # / Investigator 46969
city: Kanagawa
country: Japan
facility: Site Ref # / Investigator 46927
city: Kochi
country: Japan
facility: Site Ref # / Investigator 46984
city: Kyoto
country: Japan
facility: Site Ref # / Investigator 46981
city: Miyagi
country: Japan
facility: Site Ref # / Investigator 46921
city: Okayama
country: Japan
facility: Site Ref # / Investigator 46983
city: Osaka
country: Japan
facility: Site Ref # / Investigator 46966
city: Osaka
country: Japan
facility: Site Ref # / Investigator 46967
city: Shiga
country: Japan
facility: Site Ref # / Investigator 46980
city: Shizuoka
country: Japan
facility: Site Ref # / Investigator 46964
city: Tokyo
country: Japan
facility: Site Ref # / Investigator 46923
city: Tokyo
country: Japan
facility: Site Ref # / Investigator 46924
city: Tokyo
country: Japan
facility: Site Ref # / Investigator 46975
city: Tokyo
country: Japan
facility: Site Ref # / Investigator 46976
Study officials:
affiliation: Abbott
name: Kazuko Kobayashi
role: STUDY_DIRECTOR
References:
citation: Watanabe M, Hibi T, Mostafa NM, Chao J, Arora V, Camez A, Petersson J, Thakkar R. Long-term safety and efficacy of adalimumab in Japanese patients with moderate to severe Crohn's disease. J Crohns Colitis. 2014 Nov;8(11):1407-16. doi: 10.1016/j.crohns.2014.04.012. Epub 2014 May 27.
citation: Watanabe M, Hibi T, Lomax KG, Paulson SK, Chao J, Alam MS, Camez A; Study Investigators. Adalimumab for the induction and maintenance of clinical remission in Japanese patients with Crohn's disease. J Crohns Colitis. 2012 Mar;6(2):160-73. doi: 10.1016/j.crohns.2011.07.013. Epub 2011 Aug 26.