A Study of Adalimumab in Japanese Subjects With Rheumatoid Arthritis

This study has been completed.
Sponsor:
Collaborator:
Eisai Co., Ltd.
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT00870467
First received: March 26, 2009
Last updated: August 1, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Biological: Double-blind adalimumab
Drug: Double-blind Placebo
Biological: Open-label Adalimumab
Biological: Open-labelAdalimumabRescue
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 Phase 3 Multi-Center, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study Comparing Adalimumab and Placebo in Adult Japanese Subjects With Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Abbott:

Primary Outcome Measures:
  • Change From Baseline in Modified Total Sharp X-Ray Score at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants Meeting ACR20 Response Criteria at Week 26 (ACR: American College of Rheumatology) [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Meeting ACR50 Response Criteria at Week 26 (ACR: American College of Rheumatology) [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Meeting ACR70 Response Criteria at Week 26 (ACR: American College of Rheumatology) [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Modified Total Sharp X-Ray Score at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Meeting ACR20 Response Criteria at Week 52 (ACR: American College of Rheumatology) [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Meeting ACR50 Response Criteria at Week 52 (ACR: American College of Rheumatology) [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Meeting ACR70 Response Criteria at Week 52 (ACR: American College of Rheumatology) [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) While Receiving Adalimumab Through Week 52 [ Time Frame: Through Week 52 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 334
Study Start Date: March 2009
Study Completion Date: August 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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:
  • ABT-D2E7
  • adalimumab
  • 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 Name: 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:
  • ABT-D2E7
  • adalimumab
  • 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 Name: 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:
  • ABT-D2E7
  • adalimumab
  • 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:
  • ABT-D2E7
  • adalimumab
  • 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 Name: 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:
  • ABT-D2E7
  • adalimumab
  • 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:
  • ABT-D2E7
  • adalimumab
  • Humira

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00870467

  Show 88 Study Locations
Sponsors and Collaborators
Abbott
Eisai Co., Ltd.
Investigators
Study Director: Hiroshi Ukai, BS Abbott Japan Co.,Ltd
  More Information

No publications provided

Responsible Party: Abbott
ClinicalTrials.gov Identifier: NCT00870467     History of Changes
Other Study ID Numbers: M06-859
Study First Received: March 26, 2009
Results First Received: March 9, 2012
Last Updated: August 1, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Abbott:
Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 31, 2014