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

February 1, 2012 updated by: Abbott

A Multi-Center, Randomized, Double-blind, Placebo-controlled Study of Adalimumab for the Maintenance of Clinical Remission in Japanese Subjects With Crohn's Disease

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 75 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: DB Adalimumab 40 mg eow
Subjects received double-blind (DB) 40 mg adalimumab subcutaneously (SC) every other week (eow) during the DB treatment period lasting 52 weeks.
Biological: adalimumab
Subcutaneous injection of 40 mg adalimumab (0.8 mL/injection) every other week (eow)
Other Names:
  • Humira
  • D2E7
PLACEBO_COMPARATOR: Placebo eow
Subjects received placebo subcutaneously (SC) every other week (eow) during the double-blind treatment period lasting 52 weeks.
Other: Placebo
Subcutaneous injection of placebo (0.8 mL/injection) every other week (eow)
EXPERIMENTAL: OL Adalimumab 40 mg eow
Subjects received open-label (OL) 40 mg adalimumab subcutaneously (SC) every other week (eow) during the double-blind treatment period lasting 52 weeks.
Biological: adalimumab
Subcutaneous injection of 40 mg adalimumab (0.8 mL/injection) every other week (eow)
Other Names:
  • Humira
  • D2E7

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Had Clinical Remission at Week 52 of Double-blind Treatment
Time Frame: 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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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
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
Time Frame: 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
Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment
Time Frame: 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
Number of Participants Who Had Clinical Remission at Week 52 of Open-label Treatment
Time Frame: 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
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
Time Frame: 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
Change in Inflammatory Bowel Disease Questionnaire (IBDQ) From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment
Time Frame: 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
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
Time Frame: Baseline of 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
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
Time Frame: Baseline of 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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Had Clinical Remission at Week 148
Time Frame: Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
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 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
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
Time Frame: Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
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 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
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
Time Frame: Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
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 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 148
Time Frame: Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
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/apthous 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 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
Change in International Organization for the Study of Inflammatory Bowel Disease (IOIBD) Score From Baseline of Lead-in Study (NCT00445939) to Week 148
Time Frame: Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
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 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
Change in Inflammatory Bowel Disease Questionnaire (IBDQ) From Baseline of Lead-in Study (NCT00445939) to Week 148
Time Frame: Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
IBDQ is a validated disease-specific instrument that assesses the impact of IBD on patient quality of life during a 2-week recall period with 32 questions about bowel function and related symptoms & their social/emotional impact. Per item, participants select 1 of 7 responses (1=poor quality of life [e.g., feeling of fatigue "all of the time"]; 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 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
Change in Physical Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 148
Time Frame: Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
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 to 100, with 0=Poorest Health and 100=Best Health.
Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
Change in Mental Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 148
Time Frame: Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)
The Short Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 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 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abbott

Collaborators

Eisai Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (ACTUAL)

March 1, 2009

Study Completion (ACTUAL)

November 1, 2010

Study Registration Dates

First Submitted

March 7, 2007

First Submitted That Met QC Criteria

March 7, 2007

First Posted (ESTIMATE)

March 9, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

February 2, 2012

Last Update Submitted That Met QC Criteria

February 1, 2012

Last Verified

February 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M06-837

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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