A Study of Adalimumab for the Maintenance of Clinical Remission in Japanese Subjects With Crohn's Disease

Crohn's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00445432
• Other study ID #: M06-837
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: March 7, 2007
• Last updated: February 1, 2012
• Start date: March 2007
• Est. completion date: November 2010

Study information

• Verified date: February 2012
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: November 2010
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Biological:
• adalimumab
Subcutaneous injection of 40 mg adalimumab (0.8 mL/injection) every other week (eow)

Other:
• Placebo
Subcutaneous injection of placebo (0.8 mL/injection) every other week (eow)

Locations

Country	Name	City	State
Japan	Site Ref # / Investigator 46965	Aichi
Japan	Site Ref # / Investigator 46977	Aichi
Japan	Site Ref # / Investigator 46978	Aichi
Japan	Site Ref # / Investigator 46979	Aichi
Japan	Site Ref # / Investigator 46922	Chiba
Japan	Site Ref # / Investigator 46974	Chiba
Japan	Site Ref # / Investigator 46970	Ehime
Japan	Site Ref # / Investigator 46971	Fukuoka
Japan	Site Ref # / Investigator 46985	Fukuoka
Japan	Site Ref # / Investigator 46986	Fukuoka
Japan	Site Ref # / Investigator 46987	Fukuoka
Japan	Site Ref # / Investigator 46968	Hiroshima
Japan	Site Ref # / Investigator 46973	Hokkaido
Japan	Site Ref # / Investigator 6881	Hokkaido
Japan	Site Ref # / Investigator 46982	Hyogo
Japan	Site Ref # / Investigator 46969	Kagawa
Japan	Site Ref # / Investigator 46927	Kanagawa
Japan	Site Ref # / Investigator 46984	Kochi
Japan	Site Ref # / Investigator 46981	Kyoto
Japan	Site Ref # / Investigator 46921	Miyagi
Japan	Site Ref # / Investigator 46983	Okayama
Japan	Site Ref # / Investigator 46966	Osaka
Japan	Site Ref # / Investigator 46967	Osaka
Japan	Site Ref # / Investigator 46980	Shiga
Japan	Site Ref # / Investigator 46964	Shizuoka
Japan	Site Ref # / Investigator 46923	Tokyo
Japan	Site Ref # / Investigator 46924	Tokyo
Japan	Site Ref # / Investigator 46975	Tokyo
Japan	Site Ref # / Investigator 46976	Tokyo

Sponsors (2)

Lead Sponsor	Collaborator
Abbott	Eisai Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Had Clinical Remission at Week 52 of Double-blind Treatment	Clinical remission=Crohn's Disease (CD) Activity Index (CDAI) <150; 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 are documented during 1-week assessment period. CDAI total score is >= 0 and without upper limit. Low score=less severe CD activity. Decrease indicates improvement.	Week 52 of double-blind treatment	No
Secondary	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	Crohn's Disease Activity Index (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. CDAI has a total score >= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.	Week 52 of double-blind treatment	No
Secondary	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	Crohn's Disease Activity Index (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. CDAI has a total score >= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.	Week 52 of double-blind treatment	No
Secondary	Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	Crohn's Disease Activity Index (CDAI) is a measure of disease severity. 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 are documented during 1-week assessment period. CDAI has a total score >= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.	Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment	No
Secondary	Number of Participants Who Had Clinical Remission at Week 52 of Open-label Treatment	Clinical remission=Crohn's Disease (CD) Activity Index (CDAI) <150; 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 are documented during 1-week assessment period. CDAI total score is >= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.	Week 52 of open-label treatment	No
Secondary	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	The International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score is an indicator of the activity of Crohn's disease. It measures absence (score of 0) or presence (score of 1) of abdominal pain, diarrhea or bloody stools more than 6 times per day, anal lesion, anal fistula, other complication, abdominal mass, weight loss, fever above 38 degrees Centigrade, abdominal tenderness, and blood pigment below 10 g/dL. Total possible score=0 to 10; low score=less disease activity. Decrease in score indicates alleviation of the disease; increase indicates aggravation of disease.	Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment	No
Secondary	Change in Inflammatory Bowel Disease Questionnaire (IBDQ) From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	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 item, participants select 1 of 7 responses. 1=poor quality of life (e.g., feeling of fatigue "all of the time") and 7=good quality (e.g., feeling of fatigue "none of the time"). Scoring range = 32 to 224. Higher scores indicate better quality of life; increases in IBDQ = improved overall quality of life.	Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment	No
Secondary	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	The Short-Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 score indicates alleviation of the disease and a decrease in score indicates aggravation of disease. The physical component reflects activity level, activity limitations, pain, and rating of one's health. Score on the physical component ranges from 0 (Poorest Health) to 100 (Best Health).	Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment	No
Secondary	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	The Short-Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 score indicates alleviation of the disease and a decrease in score indicates aggravation. The mental component reflects energy/vitality, social functioning, limitations, and ratings of one's mental health. Score on mental component ranges from 0 (worst score) to 100 (best score).	Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment	No