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

NCT ID: NCT00445432

Last Updated: 2012-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2010-11-30

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.

Conditions

Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

adalimumab

Intervention Type: BIOLOGICAL

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

Placebo eow

Subjects received placebo subcutaneously (SC) every other week (eow) during the double-blind treatment period lasting 52 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Subcutaneous injection of placebo (0.8 mL/injection) every other week (eow)

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.

Group Type: EXPERIMENTAL

adalimumab

Intervention Type: BIOLOGICAL

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

Interventions

adalimumab

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

Intervention Type: BIOLOGICAL

Placebo

Subcutaneous injection of placebo (0.8 mL/injection) every other week (eow)

Intervention Type: OTHER

Other Intervention Names

Humira; D2E7

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

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Abbott

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kazuko Kobayashi

Role: STUDY_DIRECTOR

Abbott

Locations

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

Hyōgo, , 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

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 24874893 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22325170 (View on PubMed)

Other Identifiers

M06-837

Identifier Type: -

Identifier Source: org_study_id