Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Adalimumab in Japanese Subjects With Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00870467
Recruitment Status : Completed
First Posted : March 27, 2009
Results First Posted : April 5, 2012
Last Update Posted : August 7, 2012
Sponsor:
Collaborator:
Eisai Co., Ltd.
Information provided by (Responsible Party):
Abbott

Tracking Information
First Submitted Date  ICMJE March 26, 2009
First Posted Date  ICMJE March 27, 2009
Results First Submitted Date  ICMJE March 9, 2012
Results First Posted Date  ICMJE April 5, 2012
Last Update Posted Date August 7, 2012
Study Start Date  ICMJE March 2009
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 1, 2012)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 26, 2009)
Change from Baseline in modified Toral Sharp Score [ Time Frame: Week 26 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2012)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2009)
  • ACR20 [ Time Frame: Week 26 ]
  • ACR50 [ Time Frame: Week26 ]
  • ACR70 [ Time Frame: Week26 ]
  • Evaluation of adverse event, vital sign and laboratory tests [ Time Frame: During study period ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Adalimumab in Japanese Subjects With Rheumatoid Arthritis
Official Title  ICMJE A Phase 3 Multi-Center, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study Comparing Adalimumab and Placebo in Adult Japanese Subjects With Rheumatoid Arthritis
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Biological: Double-blind adalimumab
    Double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow)
    Other Name: ABT-D2E7, adalimumab, Humira
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Double-blind 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.
    Intervention: Biological: Double-blind adalimumab
  • 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.
    Interventions:
    • Biological: Double-blind adalimumab
    • Biological: Open-label Adalimumab
  • 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.
    Interventions:
    • Drug: Double-blind Placebo
    • Biological: Open-label Adalimumab
  • 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.
    Interventions:
    • Biological: Double-blind adalimumab
    • Biological: Open-label Adalimumab
    • Biological: Open-labelAdalimumabRescue
  • 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.
    Interventions:
    • Drug: Double-blind Placebo
    • Biological: Open-label Adalimumab
    • Biological: Open-labelAdalimumabRescue
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 5, 2011)
334
Original Estimated Enrollment  ICMJE
 (submitted: March 26, 2009)
300
Actual Study Completion Date  ICMJE August 2011
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00870467
Other Study ID Numbers  ICMJE M06-859
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Abbott
Study Sponsor  ICMJE Abbott
Collaborators  ICMJE Eisai Co., Ltd.
Investigators  ICMJE
Study Director: Hiroshi Ukai, BS Abbott Japan Co.,Ltd
PRS Account Abbott
Verification Date August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP