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

This study has been completed.
Sponsor:
Collaborator:
Eisai Co., Ltd.
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT00445432
First received: March 7, 2007
Last updated: February 1, 2012
Last verified: February 2012
  Purpose

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


Condition Intervention Phase
Crohn's Disease
Biological: adalimumab
Other: Placebo
Phase 2
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Abbott:

Primary Outcome Measures:
  • Number of Participants Who Had Clinical Remission at Week 52 of Double-blind Treatment [ Time Frame: Week 52 of double-blind treatment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Who Had Clinical Remission at Week 52 of Open-label Treatment [ Time Frame: Week 52 of open-label treatment ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).


Enrollment: 82
Study Start Date: March 2007
Study Completion Date: November 2010
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • adalimumab
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)
Other Name: placebo
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
  • adalimumab

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

Ages Eligible for Study:   15 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00445432

Locations
Japan
Site Ref # / Investigator 46977
Aichi, Japan
Site Ref # / Investigator 46978
Aichi, Japan
Site Ref # / Investigator 46979
Aichi, Japan
Site Ref # / Investigator 46965
Aichi, Japan
Site Ref # / Investigator 46974
Chiba, Japan
Site Ref # / Investigator 46922
Chiba, Japan
Site Ref # / Investigator 46970
Ehime, Japan
Site Ref # / Investigator 46986
Fukuoka, Japan
Site Ref # / Investigator 46985
Fukuoka, Japan
Site Ref # / Investigator 46987
Fukuoka, Japan
Site Ref # / Investigator 46971
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, Japan
Sponsors and Collaborators
Abbott
Eisai Co., Ltd.
Investigators
Study Director: Kazuko Kobayashi Abbott
  More Information

No publications provided by Abbott

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Abbott
ClinicalTrials.gov Identifier: NCT00445432     History of Changes
Other Study ID Numbers: M06-837
Study First Received: March 7, 2007
Results First Received: March 31, 2010
Last Updated: February 1, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Crohn Disease
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014