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A Phase III Study of Abatacept in Japanese Subjects With Rheumatoid Arthritis

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Abatacept
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  • The participants who completed the 169 days, full study period of Phase II (IM101-071) and were not administered other biologics between completion of IM101-071 and registration of this long-term study.
  • The participants of the Phase I study (IM101-034), who received abatacept, except participants who were withdrawn from the study due to safety problems related to abatacept.
  • New subjects with MTX intolerance: rheumatoid arthritis (RA) patients to whom MTX cannot be administered for safety reasons and who present an inadequate response to disease-modifying antirheumatic drugs (DMARDs;excluding MTX) or biologics (new subjects with MTX intolerance: RA patients who present an inadequate response to DMARDs).

Exclusion Criteria

  • Women of childbearing potential (WOCBP) who were unwilling or unable to use an acceptable method of contraception.
  • Participants who have received non approved or investigational biologics (other than abatacept from previous or ongoing studies in Japan) at registration.
  • Participants who have received treatment with any investigational drug within 56 days before registration or five half-lives (whichever is the longest).
  • Participants currently receiving treatment with leflunomide, mycophenolate mofetil, calcineurine inhibitors such as cyclosporine and tacrolimus, D-Penicillamine, Cyclophosphamide, or immunoadsorption columns.
  • The participants who completed Phase II (IM101-071) are not applicable in the following instances at time of registration: with active vasculitis, symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, breast cancer, or a history of cancer within the last 5 years, evidence of active or latent bacterial , viral infections, any serious or chronic, at risk of tuberculosis (TB), with any opportunistic infections, laboratory values of hemoglobin < 8.5 g/dL, white blood cells (WBC) < 3,000/mm^3, Platelets < 100,000/mm^3, Serum creatinine > 2 times upper limit of normal (ULN), Serum alanine transaminase or aspartate aminotransferase > 2 times ULN.

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm 1: Participants from Phase I study (IM101-034)

Arm 2: Participants from Phase II study (IM101-071)

Arm 3: New Participants with Methotrexate (MTX) Intolerance

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to AEs
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. Both subjective and objective AEs and SAEs are included.
Number of Participants With Abnormal Laboratory Changes (ALC)
The laboratory tests were analyses included enzyme, gastrointestinal, hematology, hepatobiliary, lipid, metabolic, nutritional, blood gas, microbiology, serology, protein, chemistry, renal, urinary tract, urinalyses, water, electrolyte and mineral investigations.
Number of Participants With Vital Signs, Physical Examinations, and Electrocardiogram Findings That Were Considered to be AEs by the Investigator

Secondary Outcome Measures

Percentage of Participants With American College of Rheumatology (ACR 20) Response Over Time
ACR 20 response requires a participant to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease activity, participant global assessment of disease activity, participant global assessment of pain, C-reactive protein, and degree of disability in Health Assessment Questionnaire score.
Percentage of Participants With ACR 50 Response Over Time
ACR 50 response requires a participant to have a 50% reduction in the number of swollen and tender joints, and a reduction of 50% in three of the following five parameters: physician global assessment of disease activity, participant global assessment of disease activity, participant global assessment of pain, C-reactive protein, and degree of disability in Health Assessment Questionnaire score.
Percentage of Participants With ACR 70 Response Over Time
ACR 70 response requires a participant to have a 70% reduction in the number of swollen and tender joints, and a reduction of 70% in three of the following five parameters: physician global assessment of disease activity, participant global assessment of disease activity, participant global assessment of pain, C-reactive protein, and degree of disability in Health Assessment Questionnaire score.
Baseline (BL) and Postbaseline (PBL) Disease Activity Scores (DAS 28)
The DAS 28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale of 100 mm. The DAS28 has numeric thresholds that define high disease activity (change of > 5.1), low disease activity (change of ≤ 3.2) and remission (< 2.6). Please see outcome 8 for change from BL data.
Change From Baseline in DAS 28 Scores at Week 24, 48, 96, 144, and 192
The DAS 28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale of 100 mm. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Please refer to outcome 7 for BL and PBL values.
Number of Participants With DAS 28 Score Change ≥ 1.2 From Baseline at Weeks 24, 48, 96, 144, and 192
The DAS 28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale. Participants with DAS 28 score change ≥ 1.2 from BL were considered to have improvement.
Number of Participants With Low Disease Activity Score (DAS 28 Score ≤ 3.2) at Weeks 24, 48, 96, 144, 192
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale. Participants with DAS 28 score ≤ 3.2 were considered to have low disease activity.
Number of Participants in Remission (DAS 28 Score < 2.6) at Weeks 24, 48, 96, 144, 192
The DAS 28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale. Participants with DAS 28 score < 2.6 were considered to be in remission.
Percentage of Participants Who Achieved a Reduction of At Least 0.3 Units From Baseline in Health Assessment Questionnaire (HAQ) at Weeks 24, 48, 96, 144, 192
The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from BL in HAQ.
Baseline and Postbaseline Physical Component Summary (PCS) of Health-Related Quality of Life (SF-36) Scores
The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role functioning [physical], bodily pain, and general health) and 4 mental subscales (vitality, social function, role emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from 0 to 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.Please see outcome 14 for change from BL data.
Change From Baseline in Physical Component Summary (PCS) of Health-Related Quality of Life (SF-36) Score at Weeks 24, 48, 96, 144, and 192
The SF-36 covers 8 health dimensions including 4 physical (physical function, role functioning [physical], bodily pain, and general health) and 4 mental subscales (vitality, social function, role emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, higher score indicating better quality of life. Improvements of >3 points were considered clinically meaningful. Please see outcome 13 for BL and PBL values.
Baseline and Postbaseline Mental Component Summary (MCS) of Health-Related Quality of Life (SF-36) Scores
The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role functioning [physical], bodily pain, and general health) and 4 mental subscales (vitality, social function, role emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from 0 to 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful. Please see outcome 14 for change from BL data.
Change From Baseline in Mental Component Summary (MCS) of Health-Related Quality of Life (SF-36) Score at Weeks 24, 48, 96, 144, and 192
The SF-36 covers 8 health dimensions including 4 physical (physical function, role functioning [physical], bodily pain, and general health) and 4 mental subscales (vitality, social function, role emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.Please see outcome 15 for BL and PBL values.
Baseline and Postbaseline C-reactive Protein (CRP) Levels
CRP is an acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA) and is a core component of the ACR scoring system. CRP was evaluated from serum samples. Increasing levels indicate increasing level of disease. Please see outcome 18 for change from BL data.
Percentage Decrease in C-reactive Protein Levels From Baseline at Weeks 24, 48, 96, 144, and 192
CRP is an acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA) and is a core component of the ACR scoring system. CRP was evaluated from serum samples. Increasing levels indicate increasing level of disease, negative values indicate improvement. Percentage improvement from BL = (BL - PBL value) / BL value * 100. Please refer to outcome 17 for BL and PBL values.
Baseline and Postbaseline Rheumatoid Factor Levels
Rheumatoid factor (RF or RhF) is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process. RF levels are considered positive if value is >20 and considered negative if value is <20. Please see outcome 20 for change from BL data.
Change From Baseline in Rheumatoid Factor Levels at Weeks 24, 48, 96, 144, and 192
RF is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process. RF levels are considered positive if value is >20 and considered negative if value is <20. Please refer to outcome 19 for BL and PBL values.
Number of Participants Who Were Positive for Anti-abatacept and Anti-CTLA4-T Antibodies
Validated enzyme-linked immunoassay (ELISA) method was used to measure anti-abatacept and anti-CTLA4-T antibody levels. For anti-abatacept antibody ELISA, a sample was considered seropositive if it had a titer of 400 or greater and if immunodepletion was observed. The responses that were negative in initial screen were reported as seronegative with a value of < 400. A sample was considered positive in CTLA4-T antibody ELISA if it had a titer of 25 or greater and if immunodepletion was observed.
Abatacept PK Parameter: Total Body Clearance
Total body clearance is the rate and extent at which the drug is eliminated from the body. The clearance of a drug is used to understand the processes involved in drug elimination, distribution and metabolism.
Abatacept PK Parameter: Area Under the Serum Concentration-time Curve at Steady State
Area under the plasma concentration-time curve (AUCss) at steady state for each dosing interval was determined using the linear trapezoidal rule.
Abatacept PK Parameter: Maximum Serum Concentration at Steady State
Maximum plasma concentration is the maximum observed serum drug concentration at steady state (Css max).
Abatacept PK Parameter: Minimum Plasma Concentration at Steady State
Minimum Plasma Concentration (Cmin) is the minimum observed serum drug concentration at steady state.

Full Information

First Posted
June 7, 2007
Last Updated
June 18, 2013
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT00484289
Brief Title
A Phase III Study of Abatacept in Japanese Subjects With Rheumatoid Arthritis
Official Title
A Phase III, Multi-center, Open-label, Uncontrolled, Long-term Study to Evaluate the Safety of Abatacept (BMS-188667) in Japanese Subjects With Rheumatoid Arthritis Having Completed Clinical Studies IM101-071, IM101-034, and Also Special DMARD Failures
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to demonstrate the safety of chronic use of abatacept in Japanese Subjects with Rheumatoid Arthritis (RA) having completed clinical studies IM101-071, IM101-034, and also Disease Modifying Anti-Rheumatic Drugs (DMARDs) failures with MTX intolerance.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
217 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Participants from Phase I study (IM101-034)
Arm Type
Experimental
Arm Title
Arm 2: Participants from Phase II study (IM101-071)
Arm Type
Experimental
Arm Title
Arm 3: New Participants with Methotrexate (MTX) Intolerance
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Abatacept
Other Intervention Name(s)
Orencia®, BMS-188667
Intervention Description
Vials (250 mg/vial), Intravenous, Weight-tiered dose of abatacept (equivalent to 10 mg/kg) based on their body weight at the enrollment visit; 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1,000 mg for participants > 100 kg, administered over a period of approximately 30 minutes at week 0, 2, 4 and every 4 weeks thereafter, until approved in Japan and was continued as a post-marketing study until the completion of the shift to a commercially available product.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to AEs
Description
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. Both subjective and objective AEs and SAEs are included.
Time Frame
From initiation of the study drug (31 Mar 2008) to data cutoff (27 Dec 2010). The overall mean duration of exposure to the study drug was approximately 3 years (34.3 ± 10.7 months).
Title
Number of Participants With Abnormal Laboratory Changes (ALC)
Description
The laboratory tests were analyses included enzyme, gastrointestinal, hematology, hepatobiliary, lipid, metabolic, nutritional, blood gas, microbiology, serology, protein, chemistry, renal, urinary tract, urinalyses, water, electrolyte and mineral investigations.
Time Frame
From initiation of the study drug (31 Mar 2008) to data cutoff (27 Dec 2010). The overall mean duration of exposure to the study drug was approximately 3 years (34.3 ± 10.7 months).
Title
Number of Participants With Vital Signs, Physical Examinations, and Electrocardiogram Findings That Were Considered to be AEs by the Investigator
Time Frame
At week 0, 2, 4; then once every 4 weeks up to 48 months; then once in every 3 months or 12 weeks to end of study (27 Dec 2010). The overall mean duration of exposure to the study drug was approximately 3 years (34.3 ± 10.7 months).
Secondary Outcome Measure Information:
Title
Percentage of Participants With American College of Rheumatology (ACR 20) Response Over Time
Description
ACR 20 response requires a participant to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease activity, participant global assessment of disease activity, participant global assessment of pain, C-reactive protein, and degree of disability in Health Assessment Questionnaire score.
Time Frame
At weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192.
Title
Percentage of Participants With ACR 50 Response Over Time
Description
ACR 50 response requires a participant to have a 50% reduction in the number of swollen and tender joints, and a reduction of 50% in three of the following five parameters: physician global assessment of disease activity, participant global assessment of disease activity, participant global assessment of pain, C-reactive protein, and degree of disability in Health Assessment Questionnaire score.
Time Frame
At weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192.
Title
Percentage of Participants With ACR 70 Response Over Time
Description
ACR 70 response requires a participant to have a 70% reduction in the number of swollen and tender joints, and a reduction of 70% in three of the following five parameters: physician global assessment of disease activity, participant global assessment of disease activity, participant global assessment of pain, C-reactive protein, and degree of disability in Health Assessment Questionnaire score.
Time Frame
At weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192.
Title
Baseline (BL) and Postbaseline (PBL) Disease Activity Scores (DAS 28)
Description
The DAS 28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale of 100 mm. The DAS28 has numeric thresholds that define high disease activity (change of > 5.1), low disease activity (change of ≤ 3.2) and remission (< 2.6). Please see outcome 8 for change from BL data.
Time Frame
At BL (week 0), week 24, 48, 96, 144, and 192.
Title
Change From Baseline in DAS 28 Scores at Week 24, 48, 96, 144, and 192
Description
The DAS 28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale of 100 mm. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Please refer to outcome 7 for BL and PBL values.
Time Frame
At BL (week 0), weeks 24, 48, 96, 144, and 192.
Title
Number of Participants With DAS 28 Score Change ≥ 1.2 From Baseline at Weeks 24, 48, 96, 144, and 192
Description
The DAS 28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale. Participants with DAS 28 score change ≥ 1.2 from BL were considered to have improvement.
Time Frame
At BL (week 0), weeks 24, 48, 96, 144, and 192.
Title
Number of Participants With Low Disease Activity Score (DAS 28 Score ≤ 3.2) at Weeks 24, 48, 96, 144, 192
Description
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale. Participants with DAS 28 score ≤ 3.2 were considered to have low disease activity.
Time Frame
At weeks 24, 48, 96, 144, and 192.
Title
Number of Participants in Remission (DAS 28 Score < 2.6) at Weeks 24, 48, 96, 144, 192
Description
The DAS 28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale. Participants with DAS 28 score < 2.6 were considered to be in remission.
Time Frame
At weeks 24, 48, 96, 144, and 192.
Title
Percentage of Participants Who Achieved a Reduction of At Least 0.3 Units From Baseline in Health Assessment Questionnaire (HAQ) at Weeks 24, 48, 96, 144, 192
Description
The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from BL in HAQ.
Time Frame
At BL (week 0), weeks 24, 48, 96, 144, and 192.
Title
Baseline and Postbaseline Physical Component Summary (PCS) of Health-Related Quality of Life (SF-36) Scores
Description
The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role functioning [physical], bodily pain, and general health) and 4 mental subscales (vitality, social function, role emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from 0 to 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.Please see outcome 14 for change from BL data.
Time Frame
At BL (week 0), weeks 24, 48, 96, 144, and 192.
Title
Change From Baseline in Physical Component Summary (PCS) of Health-Related Quality of Life (SF-36) Score at Weeks 24, 48, 96, 144, and 192
Description
The SF-36 covers 8 health dimensions including 4 physical (physical function, role functioning [physical], bodily pain, and general health) and 4 mental subscales (vitality, social function, role emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, higher score indicating better quality of life. Improvements of >3 points were considered clinically meaningful. Please see outcome 13 for BL and PBL values.
Time Frame
At baseline (week 0), weeks 24, 48, 96, 144, and 192.
Title
Baseline and Postbaseline Mental Component Summary (MCS) of Health-Related Quality of Life (SF-36) Scores
Description
The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role functioning [physical], bodily pain, and general health) and 4 mental subscales (vitality, social function, role emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from 0 to 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful. Please see outcome 14 for change from BL data.
Time Frame
At BL (week 0), weeks 24, 48, 96, 144, and 192.
Title
Change From Baseline in Mental Component Summary (MCS) of Health-Related Quality of Life (SF-36) Score at Weeks 24, 48, 96, 144, and 192
Description
The SF-36 covers 8 health dimensions including 4 physical (physical function, role functioning [physical], bodily pain, and general health) and 4 mental subscales (vitality, social function, role emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.Please see outcome 15 for BL and PBL values.
Time Frame
At BL (Week 0), weeks 24, 48, 96, 144, and 192.
Title
Baseline and Postbaseline C-reactive Protein (CRP) Levels
Description
CRP is an acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA) and is a core component of the ACR scoring system. CRP was evaluated from serum samples. Increasing levels indicate increasing level of disease. Please see outcome 18 for change from BL data.
Time Frame
At BL (week 0), weeks 24, 48, 96, 144, and 192.
Title
Percentage Decrease in C-reactive Protein Levels From Baseline at Weeks 24, 48, 96, 144, and 192
Description
CRP is an acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA) and is a core component of the ACR scoring system. CRP was evaluated from serum samples. Increasing levels indicate increasing level of disease, negative values indicate improvement. Percentage improvement from BL = (BL - PBL value) / BL value * 100. Please refer to outcome 17 for BL and PBL values.
Time Frame
At BL (week 0), weeks 24, 48, 96, 144, and 192.
Title
Baseline and Postbaseline Rheumatoid Factor Levels
Description
Rheumatoid factor (RF or RhF) is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process. RF levels are considered positive if value is >20 and considered negative if value is <20. Please see outcome 20 for change from BL data.
Time Frame
At BL (week 0), weeks 24, 48, 96, 144, and 192.
Title
Change From Baseline in Rheumatoid Factor Levels at Weeks 24, 48, 96, 144, and 192
Description
RF is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process. RF levels are considered positive if value is >20 and considered negative if value is <20. Please refer to outcome 19 for BL and PBL values.
Time Frame
At BL (week 0), weeks 24, 48, 96, 144, and 192.
Title
Number of Participants Who Were Positive for Anti-abatacept and Anti-CTLA4-T Antibodies
Description
Validated enzyme-linked immunoassay (ELISA) method was used to measure anti-abatacept and anti-CTLA4-T antibody levels. For anti-abatacept antibody ELISA, a sample was considered seropositive if it had a titer of 400 or greater and if immunodepletion was observed. The responses that were negative in initial screen were reported as seronegative with a value of < 400. A sample was considered positive in CTLA4-T antibody ELISA if it had a titer of 25 or greater and if immunodepletion was observed.
Time Frame
At BL (week 0), weeks 24, 48, 72, 96, 120, 144, 168, and 192.
Title
Abatacept PK Parameter: Total Body Clearance
Description
Total body clearance is the rate and extent at which the drug is eliminated from the body. The clearance of a drug is used to understand the processes involved in drug elimination, distribution and metabolism.
Time Frame
Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
Title
Abatacept PK Parameter: Area Under the Serum Concentration-time Curve at Steady State
Description
Area under the plasma concentration-time curve (AUCss) at steady state for each dosing interval was determined using the linear trapezoidal rule.
Time Frame
Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
Title
Abatacept PK Parameter: Maximum Serum Concentration at Steady State
Description
Maximum plasma concentration is the maximum observed serum drug concentration at steady state (Css max).
Time Frame
Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
Title
Abatacept PK Parameter: Minimum Plasma Concentration at Steady State
Description
Minimum Plasma Concentration (Cmin) is the minimum observed serum drug concentration at steady state.
Time Frame
Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria The participants who completed the 169 days, full study period of Phase II (IM101-071) and were not administered other biologics between completion of IM101-071 and registration of this long-term study. The participants of the Phase I study (IM101-034), who received abatacept, except participants who were withdrawn from the study due to safety problems related to abatacept. New subjects with MTX intolerance: rheumatoid arthritis (RA) patients to whom MTX cannot be administered for safety reasons and who present an inadequate response to disease-modifying antirheumatic drugs (DMARDs;excluding MTX) or biologics (new subjects with MTX intolerance: RA patients who present an inadequate response to DMARDs). Exclusion Criteria Women of childbearing potential (WOCBP) who were unwilling or unable to use an acceptable method of contraception. Participants who have received non approved or investigational biologics (other than abatacept from previous or ongoing studies in Japan) at registration. Participants who have received treatment with any investigational drug within 56 days before registration or five half-lives (whichever is the longest). Participants currently receiving treatment with leflunomide, mycophenolate mofetil, calcineurine inhibitors such as cyclosporine and tacrolimus, D-Penicillamine, Cyclophosphamide, or immunoadsorption columns. The participants who completed Phase II (IM101-071) are not applicable in the following instances at time of registration: with active vasculitis, symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, breast cancer, or a history of cancer within the last 5 years, evidence of active or latent bacterial , viral infections, any serious or chronic, at risk of tuberculosis (TB), with any opportunistic infections, laboratory values of hemoglobin < 8.5 g/dL, white blood cells (WBC) < 3,000/mm^3, Platelets < 100,000/mm^3, Serum creatinine > 2 times upper limit of normal (ULN), Serum alanine transaminase or aspartate aminotransferase > 2 times ULN.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution
City
Nagoya-Shi
State/Province
Aichi
ZIP/Postal Code
460-0001
Country
Japan
Facility Name
Local Institution
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466-8550
Country
Japan
Facility Name
Local Institution
City
Goshogawara-Shi
State/Province
Aomori
ZIP/Postal Code
037-0053
Country
Japan
Facility Name
Local Institution
City
Chiba-Shi
State/Province
Chiba
Country
Japan
Facility Name
Local Institution
City
Fukui-Shi
State/Province
Fukui
ZIP/Postal Code
910-0041
Country
Japan
Facility Name
Local Institution
City
Fukui-Shi
State/Province
Fukui
ZIP/Postal Code
9100067
Country
Japan
Facility Name
Local Institution
City
Fukui-Shi
State/Province
Fukui
ZIP/Postal Code
9103133
Country
Japan
Facility Name
Local Institution
City
Fukuoka-Shi
State/Province
Fukuoka
ZIP/Postal Code
810-0065
Country
Japan
Facility Name
Local Institution
City
Fukuoka-Shi
State/Province
Fukuoka
ZIP/Postal Code
812-0025
Country
Japan
Facility Name
Local Institution
City
Kitakyushu-Shi
State/Province
Fukuoka
ZIP/Postal Code
807-8555
Country
Japan
Facility Name
Local Institution
City
Higashi-Hiroshima-Shi
State/Province
Hiroshima
ZIP/Postal Code
739-0002
Country
Japan
Facility Name
Local Institution
City
Sapporo City
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Local Institution
City
Sapporo-City
State/Province
Hokkaido
ZIP/Postal Code
060-0001
Country
Japan
Facility Name
Local Institution
City
Sapporo-City
State/Province
Hokkaido
ZIP/Postal Code
060-8604
Country
Japan
Facility Name
Local Institution
City
Kanzaki-Gun
State/Province
Hyogo
ZIP/Postal Code
679-2414
Country
Japan
Facility Name
Local Institution
City
Kato-Gun
State/Province
Hyogo
ZIP/Postal Code
673-1462
Country
Japan
Facility Name
Local Institution
City
Hitachi-Shi
State/Province
Ibaraki
ZIP/Postal Code
316-0035
Country
Japan
Facility Name
Local Institution
City
Tsukuba-Shi
State/Province
Ibaraki
ZIP/Postal Code
305-0005
Country
Japan
Facility Name
Local Institution
City
Sagamihara-Shi
State/Province
Kanagawa
ZIP/Postal Code
228-8522
Country
Japan
Facility Name
Local Institution
City
Sendai-Shi
State/Province
Miyagi
ZIP/Postal Code
981-0911
Country
Japan
Facility Name
Local Institution
City
Sendai-Shi
State/Province
Miyagi
ZIP/Postal Code
982-0032
Country
Japan
Facility Name
Local Institution
City
Sendai
State/Province
Miyagi
Country
Japan
Facility Name
Local Institution
City
Nagano-Shi
State/Province
Nagano
ZIP/Postal Code
380-8582
Country
Japan
Facility Name
Local Institution
City
Tsukubo-Gun
State/Province
Okayama
ZIP/Postal Code
701-0304
Country
Japan
Facility Name
Local Institution
City
Kawachinagano-Shi
State/Province
Osaka
ZIP/Postal Code
86-0008
Country
Japan
Facility Name
Local Institution
City
Ureshino-Shi
State/Province
Saga
ZIP/Postal Code
843-0301
Country
Japan
Facility Name
Local Institution
City
Iruma-Gun
State/Province
Saitama
ZIP/Postal Code
350-0495
Country
Japan
Facility Name
Local Institution
City
Kawagoe-Shi
State/Province
Saitama
ZIP/Postal Code
350-8550
Country
Japan
Facility Name
Local Institution
City
Kitamoto-Shi
State/Province
Saitama
ZIP/Postal Code
364-0026
Country
Japan
Facility Name
Local Institution
City
Hamamatsu-Shi
State/Province
Shizuoka
ZIP/Postal Code
430-0906
Country
Japan
Facility Name
Local Institution
City
Kawachigun
State/Province
Tochigi
ZIP/Postal Code
329-1104
Country
Japan
Facility Name
Local Institution
City
Shimotsuke-Shi
State/Province
Tochigi
ZIP/Postal Code
3290498
Country
Japan
Facility Name
Local Institution
City
Arakawa-Ku
State/Province
Tokyo
ZIP/Postal Code
116-0011
Country
Japan
Facility Name
Local Institution
City
Bunkyo-Ku
State/Province
Tokyo
ZIP/Postal Code
113-0022
Country
Japan
Facility Name
Local Institution
City
Bunkyo-Ku
State/Province
Tokyo
ZIP/Postal Code
113-8519
Country
Japan
Facility Name
Local Institution
City
Setagaya-Ku
State/Province
Tokyo
ZIP/Postal Code
155-0032
Country
Japan
Facility Name
Local Institution
City
Shinjuku-Ku
State/Province
Tokyo
ZIP/Postal Code
162-0054
Country
Japan
Facility Name
Local Institution
City
Takaoka-Shi
State/Province
Toyama
ZIP/Postal Code
933-8525
Country
Japan
Facility Name
Local Institution
City
Chiba-Shi
ZIP/Postal Code
260-0801
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
24754273
Citation
Takeuchi T, Matsubara T, Urata Y, Suematsu E, Ohta S, Honjo S, Abe T, Yamamoto A, Miyasaka N; Japan Abatacept Study Group. Phase III, multicenter, open-label, long-term study of the safety of abatacept in Japanese patients with rheumatoid arthritis and an inadequate response to conventional or biologic disease-modifying antirheumatic drugs. Mod Rheumatol. 2014 Sep;24(5):744-53. doi: 10.3109/14397595.2014.899179. Epub 2014 Apr 23.
Results Reference
derived

Learn more about this trial

A Phase III Study of Abatacept in Japanese Subjects With Rheumatoid Arthritis

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