A Study of Adalimumab in Japanese Subjects With Rheumatoid Arthritis

August 1, 2012 updated by: Abbott

A Phase 3 Multi-Center, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study Comparing Adalimumab and Placebo in Adult Japanese Subjects With Rheumatoid Arthritis

To evaluate the potential of adalimumab to inhibit radiographic progression in joint destruction compared with placebo in adult Japanese subjects with recent onset of rheumatoid arthritis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This was a Phase 3 multicenter, randomized, double-blind, parallel group, placebo-controlled study designed to evaluate the inhibition of radiographic progression by adalimumab compared with placebo in adult Japanese patients with early rheumatoid arthritis (RA) who had not been previously treated with methotrexate (MTX). Eligible participants were randomized 1:1 to receive either a subcutaneous injection of adalimumab 40 mg or matching placebo every other week (eow) during the 26-week double-blind phase. All participants also received 6 mg to 8 mg MTX weekly as basal treatment for their disease. Participants who experienced an increase in disease activity (more than 20% increase in tender joint count and swollen joint count) at Week 12, 16, or 20 compared with Baseline after having increased MTX dose to 8 mg per week for at least 4 weeks were discontinued from the double-blind phase and were eligible to receive open-label adalimumab 40 mg eow as rescue treatment. Participants who completed the 26 weeks of treatment (either double-blind study drug [adalimumab or placebo] treatment or open-label adalimumab treatment) were eligible to enter the 26-week open-label phase in which they received adalimumab 40 mg eow. Efficacy and safety assessments were performed at Baseline and at designated study visits.

Study Type

Interventional

Enrollment (Actual)

334

Phase

  • 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
      • Anjo, Japan
        • Site Reference ID/Investigator# 46861
      • Aomori, Japan
        • Site Reference ID/Investigator# 46919
      • Chiba, Japan
        • Site Reference ID/Investigator# 46805
      • Chiba, Japan
        • Site Reference ID/Investigator# 46806
      • Chiba, Japan
        • Site Reference ID/Investigator# 46880
      • Chiba, Japan
        • Site Reference ID/Investigator# 46881
      • Fuchu, Japan
        • Site Reference ID/Investigator# 46890
      • Fukuoka, Japan
        • Site Reference ID/Investigator# 46902
      • Fukuoka, Japan
        • Site Reference ID/Investigator# 46903
      • Fukuoka, Japan
        • Site Reference ID/Investigator# 46904
      • Gifu, Japan
        • Site Reference ID/Investigator# 46856
      • Gunma, Japan
        • Site Reference ID/Investigator# 46944
      • Hiroshima, Japan
        • Site Reference ID/Investigator# 46893
      • Hiroshima, Japan
        • Site Reference ID/Investigator# 46894
      • Hokkaido, Japan
        • Site Reference ID/Investigator# 12161
      • Hokkaido, Japan
        • Site Reference ID/Investigator# 46916
      • Hokkaido, Japan
        • Site Reference ID/Investigator# 46918
      • Hyogo, Japan
        • Site Reference ID/Investigator# 46865
      • Hyogo, Japan
        • Site Reference ID/Investigator# 46871
      • Ibaraki, Japan
        • Site Reference ID/Investigator# 46801
      • Ibaraki, Japan
        • Site Reference ID/Investigator# 46925
      • Iwate, Japan
        • Site Reference ID/Investigator# 46800
      • Kagoshima, Japan
        • Site Reference ID/Investigator# 46873
      • Kagoshima, Japan
        • Site Reference ID/Investigator# 46874
      • Kanagawa, Japan
        • Site Reference ID/Investigator# 46845
      • Kanagawa, Japan
        • Site Reference ID/Investigator# 46899
      • Kanagawa, Japan
        • Site Reference ID/Investigator# 46901
      • Kanazawa, Japan
        • Site Reference ID/Investigator# 46851
      • Kanazawa, Japan
        • Site Reference ID/Investigator# 46852
      • Kawagoe, Japan
        • Site Reference ID/Investigator# 46802
      • Kawasaki, Japan
        • Site Reference ID/Investigator# 46900
      • Kirishima, Japan
        • Site Reference ID/Investigator# 46875
      • Kitakyushu, Japan
        • Site Reference ID/Investigator# 46870
      • Kumamoto, Japan
        • Site Reference ID/Investigator# 46872
      • Kumamoto, Japan
        • Site Reference ID/Investigator# 46912
      • Kyoto, Japan
        • Site Reference ID/Investigator# 46864
      • Maebashi, Japan
        • Site Reference ID/Investigator# 46943
      • Matsuyama, Japan
        • Site Reference ID/Investigator# 46898
      • Miyazaki, Japan
        • Site Reference ID/Investigator# 46915
      • Nagano, Japan
        • Site Reference ID/Investigator# 46853
      • Nagano, Japan
        • Site Reference ID/Investigator# 46855
      • Nagasaki, Japan
        • Site Reference ID/Investigator# 46909
      • Nagasaki, Japan
        • Site Reference ID/Investigator# 46910
      • Nagasaki, Japan
        • Site Reference ID/Investigator# 46911
      • Nagoya, Japan
        • Site Reference ID/Investigator# 46858
      • Nagoya, Japan
        • Site Reference ID/Investigator# 46860
      • Nara, Japan
        • Site Reference ID/Investigator# 46877
      • Nara, Japan
        • Site Reference ID/Investigator# 46885
      • Niigata, Japan
        • Site Reference ID/Investigator# 46848
      • Niigata, Japan
        • Site Reference ID/Investigator# 46906
      • Oita, Japan
        • Site Reference ID/Investigator# 46914
      • Okayama, Japan
        • Site Reference ID/Investigator# 46869
      • Okayama, Japan
        • Site Reference ID/Investigator# 46886
      • Okayama, Japan
        • Site Reference ID/Investigator# 46887
      • Okayama, Japan
        • Site Reference ID/Investigator# 46892
      • Okinawa, Japan
        • Site Reference ID/Investigator# 46876
      • Osaka, Japan
        • Site Reference ID/Investigator# 46946
      • Osaka, Japan
        • Site Reference ID/Investigator# 46947
      • Rifu, Japan
        • Site Reference ID/Investigator# 46842
      • Sagamihara, Japan
        • Site Reference ID/Investigator# 46846
      • Saitama, Japan
        • Site Reference ID/Investigator# 46803
      • Saitama, Japan
        • Site Reference ID/Investigator# 46804
      • Saitama, Japan
        • Site Reference ID/Investigator# 46878
      • Saitama, Japan
        • Site Reference ID/Investigator# 46879
      • Sapporo, Japan
        • Site Reference ID/Investigator# 46917
      • Shimotsuke, Japan
        • Site Reference ID/Investigator# 46942
      • Shizuoka, Japan
        • Site Reference ID/Investigator# 46854
      • Shizuoka, Japan
        • Site Reference ID/Investigator# 46857
      • Shizuoka, Japan
        • Site Reference ID/Investigator# 46859
      • Takamatsu, Japan
        • Site Reference ID/Investigator# 46895
      • Tokyo, Japan
        • Site Reference ID/Investigator# 46843
      • Tokyo, Japan
        • Site Reference ID/Investigator# 46844
      • Tokyo, Japan
        • Site Reference ID/Investigator# 46850
      • Tokyo, Japan
        • Site Reference ID/Investigator# 46882
      • Tokyo, Japan
        • Site Reference ID/Investigator# 46883
      • Tokyo, Japan
        • Site Reference ID/Investigator# 46884
      • Tokyo, Japan
        • Site Reference ID/Investigator# 46888
      • Tokyo, Japan
        • Site Reference ID/Investigator# 46889
      • Tokyo, Japan
        • Site Reference ID/Investigator# 46891
      • Tokyo, Japan
        • Site Reference ID/Investigator# 46896
      • Toyama, Japan
        • Site Reference ID/Investigator# 46849
      • Toyama, Japan
        • Site Reference ID/Investigator# 46907
      • Toyoake, Japan
        • Site Reference ID/Investigator# 46862
      • Toyohashi, Japan
        • Site Reference ID/Investigator# 46866
      • Tsu, Japan
        • Site Reference ID/Investigator# 46863
      • Tsukuba, Japan
        • Site Reference ID/Investigator# 46926
      • Yokohama, Japan
        • Site Reference ID/Investigator# 46897
      • Yokohama, Japan
        • Site Reference ID/Investigator# 46905

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

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  • Rheumatoid arthritis based on the American College of Rheumatology criteria
  • Methotrexate or leflunomide naïve
  • Disease duration less than or equal to 2 years from diagnosis

Exclusion Criteria

  • History of acute inflammatory joint disease of different origin from rheumatoid arthritis, cancer, lymphoma, leukemia or lymphoproliferative disease, active TB, HIV
  • Previously received anti-TNF therapy anti-IL-6 receptor antibody, CTLA4-Ig, anti-CD20 antibody, cyclophosphamide, cyclosporine, azathioprine, or tacrolimus
  • Joint surgery involving joints to be assessed within 8 weeks prior to Screening

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 Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: DB Placebo
Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
Drug: Double-blind Placebo
Double-blind adalimumab-matching placebo administered subcutaneously (SC)every other week (eow)
Other Names:
  • Placebo
Experimental: DB adalimumab
Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
Biological: Double-blind adalimumab
Double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow)
Other Names:
  • ABT-D2E7, adalimumab, Humira
Experimental: DB Adalimumab/OL Adalimumab
Participants received double-blind adalimumab administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
Biological: Double-blind adalimumab
Double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow)
Other Names:
  • ABT-D2E7, adalimumab, Humira
Biological: Open-label Adalimumab
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study
Other Names:
  • adalimumab
  • ABT-D2E7
  • Humira
Experimental: DB Placebo/OL Adalimumab
Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
Drug: Double-blind Placebo
Double-blind adalimumab-matching placebo administered subcutaneously (SC)every other week (eow)
Other Names:
  • Placebo
Biological: Open-label Adalimumab
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study
Other Names:
  • adalimumab
  • ABT-D2E7
  • Humira
Experimental: DB Adalimumab/RE OL Adalimumab
Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible at Week 12 or after) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
Biological: Double-blind adalimumab
Double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow)
Other Names:
  • ABT-D2E7, adalimumab, Humira
Biological: Open-label Adalimumab
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study
Other Names:
  • adalimumab
  • ABT-D2E7
  • Humira
Biological: Open-labelAdalimumabRescue
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) as rescue treatment to complete the first 26 weeks in the study- dependent on participant eligibility (increase in disease activity), applies to Weeks 12 to 26
Other Names:
  • adalimumab
  • ABT-D2E7
  • Humira
Experimental: DB Placebo/RE OL Adalimumab
Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible at Week 12 or after) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
Drug: Double-blind Placebo
Double-blind adalimumab-matching placebo administered subcutaneously (SC)every other week (eow)
Other Names:
  • Placebo
Biological: Open-label Adalimumab
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study
Other Names:
  • adalimumab
  • ABT-D2E7
  • Humira
Biological: Open-labelAdalimumabRescue
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) as rescue treatment to complete the first 26 weeks in the study- dependent on participant eligibility (increase in disease activity), applies to Weeks 12 to 26
Other Names:
  • adalimumab
  • ABT-D2E7
  • Humira

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Modified Total Sharp X-Ray Score at Week 26
Time Frame: Baseline, Week 26
Modified Total Sharp Score (mTSS) is a measure of joint health, used in evaluation of inhibition of radiographic progression of disease. Digitized X-rays of hands and feet were obtained then scored in a blinded manner: for erosions (0 [no damage] to 5 [complete collapse or total destruction of joint]) and for joint space narrowing (0 [no damage] to 4 [complete luxation of joint]). Scores were added, giving total mTSS (0 [normal] to 380 [maximal disease]). Large positive change in mTSS indicates disease progression; small positive/no change indicates slowing/halting of disease progression.
Baseline, Week 26

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Meeting ACR20 Response Criteria at Week 26 (ACR: American College of Rheumatology)
Time Frame: Week 26
Patients were ACR20 responders if they had: >= 20% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=20% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant C-reactive protein. Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.
Week 26
Number of Participants Meeting ACR50 Response Criteria at Week 26 (ACR: American College of Rheumatology)
Time Frame: Week 26
Patients were ACR50 responders if they had: >= 50% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=50% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant C-reactive protein. Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.
Week 26
Number of Participants Meeting ACR70 Response Criteria at Week 26 (ACR: American College of Rheumatology)
Time Frame: Week 26
Patients were ACR70 responders if they had: >= 70% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=70% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant C-reactive protein. Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.
Week 26
Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 26
Time Frame: Baseline, Week 26
Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity.
Baseline, Week 26
Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 26
Time Frame: Week 26
Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity. DAS28(ESR) score <2.6 was defined as clinical remission of disease.
Week 26
Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) on Double-blind Study Drug Through Week 26
Time Frame: Through Week 26
Adverse events were collected at designated study visits for all participants who were randomized and received at least 1 dose of study drug. The number of participants who experienced any adverse event (serious or non-serious) while receiving double-blind study drug is summarized. See the Reported Adverse Event section for details.
Through Week 26
Change From Baseline in Modified Total Sharp X-Ray Score at Week 52
Time Frame: Baseline, Week 52
Modified Total Sharp Score (mTSS) is a measure of joint health, used in evaluation of inhibition of radiographic progression of disease. Digitized X-rays of hands and feet were obtained then scored in a blinded manner: for erosions (0 [no damage] to 5 [complete collapse or total destruction of joint]) and for joint space narrowing (0 [no damage] to 4 [complete luxation of joint]). Scores were added, giving total mTSS score (0 [normal] to 380 [maximal disease]). Large positive change in mTSS indicates diseae progression; small positive/no change indicates slowing/halting of disease progression.
Baseline, Week 52
Number of Participants Meeting ACR20 Response Criteria at Week 52 (ACR: American College of Rheumatology)
Time Frame: Week 52
Patients were ACR20 responders if they had: >=20% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=20% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.
Week 52
Number of Participants Meeting ACR50 Response Criteria at Week 52 (ACR: American College of Rheumatology)
Time Frame: Week 52
Patients were ACR50 responders if they had: >=50% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=50% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.
Week 52
Number of Participants Meeting ACR70 Response Criteria at Week 52 (ACR: American College of Rheumatology)
Time Frame: Week 52
Patients were ACR70 responders if they had: >=70% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=70% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.
Week 52
Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 52
Time Frame: Baseline, Week 52
Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity.
Baseline, Week 52
Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 52
Time Frame: Week 52
Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity. DAS28(ESR) score <2.6 was defined as clinical remission of disease.
Week 52
Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) While Receiving Adalimumab Through Week 52
Time Frame: Through Week 52
Adverse events were collected at designated study visits for all participants who were randomized and received at least 1 dose of adalimumab. The number of participants who experienced any adverse event (serious or non-serious) while receiving any adalimumab during the study (double-blind adalimumab and/or open-label) is summarized. See the Reported Adverse Event section for details.
Through Week 52

Collaborators and Investigators

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

Sponsor

Abbott

Collaborators

Eisai Co., Ltd.

Investigators

  • Study Director: Hiroshi Ukai, BS, Abbott Japan 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, 2009

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

August 1, 2011

Study Registration Dates

First Submitted

March 26, 2009

First Submitted That Met QC Criteria

March 26, 2009

First Posted (Estimate)

March 27, 2009

Study Record Updates

Last Update Posted (Estimate)

August 7, 2012

Last Update Submitted That Met QC Criteria

August 1, 2012

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M06-859

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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