- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00547521
Phase IIIB Subcutaneous Abatacept Monotherapy Study
March 13, 2015 updated by: Bristol-Myers Squibb
A Phase IIIb, Multi-center, Stratified, Open-Label Study to Evaluate the Immunogenicity, Steady State Trough Level, and Safety of Subcutaneous Abatacept (BMS-188667) in Subjects With Rheumatoid Arthritis Administered With or Without Background Methotrexate
To evaluate safety and immunogenicity of abatacept when used with or without methotrexate in the absence of an IV loading dose of abatacept
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
119
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
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Queensland
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Maroochydore, Queensland, Australia, 4558
- Local Institution
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Tasmania
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Hobart, Tasmania, Australia, 7001
- Local Institution
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Victoria
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Malvern, Victoria, Australia, 3144
- Local Institution
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Distrito Federal
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D.f., Distrito Federal, Mexico, 06700
- Local Institution
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Jalisco
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Guadalajara, Jalisco, Mexico, 44100
- Local Institution
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Kwa Zulu Natal
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Berea, Kwa Zulu Natal, South Africa, 4001
- Local Institution
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Western Cape
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Panorama, Western Cape, South Africa, 7500
- Local Institution
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Alabama
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Huntsville, Alabama, United States, 35801
- Rheumatology Associates of North Alabama
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Mobile, Alabama, United States, 36608
- Coastal Clinical Research Inc
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California
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Palo Alto, California, United States, 94304
- Stanford University School of Medicine
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Colorado
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Boulder, Colorado, United States, 80304
- Boulder Medical Center
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Florida
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Palm Harbor, Florida, United States, 34684
- The Arthritis Center
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Kentucky
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Louisville, Kentucky, United States, 40298
- Medical Towers South
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Nebraska
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Omaha, Nebraska, United States, 68114
- Westroads Medical Group
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New York
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Binghamton, New York, United States, 13905
- Regional Rheumatology Associates
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North Carolina
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Greenville, North Carolina, United States, 27834
- Physicians East, PA
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Oklahoma
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Tulsa, Oklahoma, United States, 74135
- Healthcare Research Consultants
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Pennsylvania
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Bethlehem, Pennsylvania, United States, 18015
- East Penn Rheumatology Associates
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Duncansville, Pennsylvania, United States, 16635
- Altoona Center for Clinical Research
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South Carolina
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Charleston, South Carolina, United States, 29406
- Low Country Rheumatology, PA
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Columbia, South Carolina, United States, 29204
- Columbia Arthritis Center
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Wisconsin
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Glendale, Wisconsin, United States, 53217
- Rheumatic Disease Center
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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
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Clinical diagnosis of Rheumatoid Arthritis
- Subjects Global Disease Assessment of greater than equal to 20 mm on a visual analog scale
- Discontinue all Biologics and Disease-modifying antirheumatic drugs (DMARDS) except for methotrexate
Exclusion Criteria:
- Received treatment with rituximab
- Subjects who have received treatment with immunoadsorbtion columns (such as Prosorba columns), mycophenolate mofetil (Cellcept®), cyclosporine A or other calcineurin inhibitors, or D-Penicillamine
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: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Subcutaneous (SC) Abatacept + Methotrexate (MTX) Cohort
In the ST period, participants were administered a dose of 125 mg abatacept SC, once weekly, for 4 months.
Participants were also administered a stable MTX dose of greater than or equal to 10 mg once weekly for at least 4 weeks prior to first injection of SC abatacept.
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solution, subcutaneous injection, 125 mg/kg, weekly, 106 days in short term; long term is open
Other Names:
Participants who were currently receiving methotrexate at a stable dose ≥ 10 mg for at least 4 weeks
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Experimental: SC Abatacept Monotherapy Cohort
In the ST period, participants were administered a dose of 125 mg abatacept SC, once weekly, for 4 months.
Participants did not receive MTX at screening i.e., MTX naive, or discontinued MTX due to lack of efficacy or tolerability at least 4 weeks prior to first injection of SC abatacept.
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solution, subcutaneous injection, 125 mg/kg, weekly, 106 days in short term; long term is open
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses (Enzyme-linked Immunosorbent Assay [ELISA] Method) at Day 113 of the ST Study
Time Frame: Day 113
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ELISA is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum.
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.
The responses that were negative in initial screen were reported as seronegative with a value of < 25.
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Day 113
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Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses (ELISA Method) Over Time During the ST Study
Time Frame: Day 15, 29, 43, 57, 85,113 and 28, 56, and 85 days post last dose.
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ELISA is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum.
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.
The responses that were negative in initial screen were reported as seronegative with a value of < 25.
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Day 15, 29, 43, 57, 85,113 and 28, 56, and 85 days post last dose.
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Number of Participants With Positive Anti-abatacept Responses to Abatacept (Meso-Scale Discovery [MSD] Electrochemiluminescence [ECL] Assay Method) Over Time During the ST Study
Time Frame: Day 15, 29, 43, 57, 85,113 and 28, 56 and 85 days post last dose.
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The ECL (MSD) assay method is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum.
It is more sensitive and has a higher drug tolerance than ELISA method.
For the anti-abatacept antibody ECL (MSD) assay, a sample was considered seropositive if it had a titer of 10 or greater and if immunodepletion was observed with abatacept, or abatacept and CTLA4-T.
Those responses that were not positive in the initial screen or were not confirmed to be positive based on immunodepletion were reported as seronegative and were assigned a value of < 10.
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Day 15, 29, 43, 57, 85,113 and 28, 56 and 85 days post last dose.
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Immunogenicity in MTX Naive and MTX-previous Users in Cohort 1 at Day 113 of the ST Study (for ELISA Results)
Time Frame: Day 113.
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ELISA is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum.
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.
The responses that were negative in initial screen were reported as seronegative with a value of < 25.
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Day 113.
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Immunogenicity in MTX Naive and MTX-previous Users in Cohort 1 at Day 113 of the ST Study (for MSD Results)
Time Frame: Day 113.
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The ECL (MSD) assay method is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum.
It is more sensitive and has a higher drug tolerance than the ELISA method.
For anti-abatacept antibody ECL (MSD) assay, a sample was considered seropositive if it had a titer of 10 or greater and if immunodepletion was observed with abatacept, or abatacept and CTLA4-T.
Those responses that were not positive in the initial screen or were not confirmed to be positive based on immunodepletion were reported as seronegative and were assigned a value of < 10.
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Day 113.
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Cross Tabulations of the Number of Participants With Positive and Negative Immunogenicity Status at Baseline and Each Visit During the ST Study (for ELISA Results)
Time Frame: Baseline and on day 15, 29, 43, 57, 85 and 113
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ELISA is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum.
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.
The responses that were negative in initial screen were reported as seronegative with a value of < 25.
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Baseline and on day 15, 29, 43, 57, 85 and 113
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Cross Tabulations of the Number of Participants With Positive and Negative Immunogenicity Status at Baseline and Each Visit During the ST Study (for MSD Results)
Time Frame: Baseline and day 15, 29, 43, 57, 85 and 113.
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The ECL (MSD) assay method is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum .
It is more sensitive and has a higher drug tolerance than the ELISA method.
For anti-abatacept antibody ECL(MSD) assay, a sample was considered seropositive if it had a titer of 10 or greater and if immunodepletion was observed with abatacept, or abatacept and CTLA4-T.
Those responses that were not positive in the initial screen or were not confirmed to be positive based on immunodepletion were reported as seronegative and were assigned a value of < 10.
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Baseline and day 15, 29, 43, 57, 85 and 113.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in DAS28-CRP Score at End of 4-month (Day 113) of the ST Study
Time Frame: Baseline and Month 4 (Day113).
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DAS28-CRP is a continuous variable which is a composite of 4 variables: the number of tender joint out of 28, the number of swollen joint out of 28, C-reactive protein (CRP) in milligrams/Liter (mg/L) and subject assessment of disease activity measure on a VAS of 100mm.
DAS 28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.36 * ln(CRP+1) + 0.014 * VAS + 0.96.
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Baseline and Month 4 (Day113).
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Number of Participants With Clinically Meaningful Improvement at End of 4-month (Day 113) of the ST Study
Time Frame: Day 113.
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A clinically meaningful improvement is defined as a greater than or equal to 1.2 reduction in DAS28-CRP score from baseline.
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Day 113.
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Change From Baseline in Physical Functioning (HAQ-DI) at End of the 4-month Treatment Period (Day 113) of the ST Study
Time Frame: Baseline and Month 4 (Day 113).
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HAQ-DI takes into account participant's use of aids or devices or assistance in scoring algorithm for a disability category.
The questionnaire includes 20 questions assessing physical function 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 indicate greater dysfunction.
The score is calculated by summing worst scores in each domain and dividing by the number of domains answered.
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Baseline and Month 4 (Day 113).
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Change From Baseline in All HAQ-DI Components at End of the 4-month Treatment Period (Day 113) of the ST Study
Time Frame: Baseline and Month 4 (Day113).
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HAQ-DI takes into account participant's use of aids or devices or assistance in scoring algorithm for a disability category.
The questionnaire includes 20 questions assessing physical function 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 indicate greater dysfunction.
The score is calculated by summing worst scores in each domain and dividing by the number of domains answered.
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Baseline and Month 4 (Day113).
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Cross Tabulations of Number of Participants With Positive and Negative Status for RF at Day 113 With Baseline, in the ST Study
Time Frame: Baseline and Day 113.
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RF is an autoantibody that is usually present in the serum of people with rheumatoid arthritis.
The cut-point value for seroconversion was 15 IU/mL (>= 15 IU/mL resulted in a positive result).
Cross-tabulation of frequency of seroconversion of RF at Day 113 with baseline, in the ST period, was provided.
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Baseline and Day 113.
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Number of Participants Who Died, Experienced SAEs, Experienced AEs or Who Discontinued Due to AEs During the ST Study
Time Frame: Continuously through ST period (upto Day 113). Includes the data from start of study drug therapy up to 56 days after the last dose (Day 113) or start of the long-term period whichever occurred first.
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AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug.
SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose.
Participants who discontinued the study due to any AEs or SAEs were recorded.
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Continuously through ST period (upto Day 113). Includes the data from start of study drug therapy up to 56 days after the last dose (Day 113) or start of the long-term period whichever occurred first.
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Number of Participants Who Experienced Drug-related SAEs and Drug-related AEs During the ST Study
Time Frame: Continuously through ST period (upto Day 113). Includes the data from start of study drug therapy up to 56 days after the last dose (Day 113) or start of the long-term period whichever occurred first.
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Drug-related AEs are those events with a relationship to the study therapy of certain; probable; possible; or missing.
Drug-related SAEs are those events with any relationship to the study therapy.
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Continuously through ST period (upto Day 113). Includes the data from start of study drug therapy up to 56 days after the last dose (Day 113) or start of the long-term period whichever occurred first.
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Number of Participants With AEs of Special Interest During the ST Study
Time Frame: Continuously through ST period (up to Day 113). Includes the data from start of study drug therapy up to 56 days after the last dose (Day 113) or start of the long-term period whichever occurred first.
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An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug).
For this study, AEs of particular importance were associated with the use of immunomodulatory agents: infections, autoimmune disorders, malignancies, and injection reaction AEs (systemic AEs occurring within 24 hours of SC injection and local injection site reactions) were recorded.
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Continuously through ST period (up to Day 113). Includes the data from start of study drug therapy up to 56 days after the last dose (Day 113) or start of the long-term period whichever occurred first.
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Number of Participants With Marked Abnormalities (MAs) in Hematology During the ST Study: Hemoglobin, Hematocrit, Platelet Count, Erythrocytes and Leukocytes
Time Frame: Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.
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MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point.
The following hematology MA definitions specify the criteria for the data presented.
Hemoglobin: >3 g/dL decrease from pre-treatment (pre Rx); hematocrit: <0.75 * pre-Rx value; platelet count: <0.67 * (LLN -lower limit of normal) (or, if pre-Rx value <LLN, then <0.5 * pre-Rx value and <100,000/mm^3); leukocytes: <0.75 * LLN or >1.25 * ULN (or, if pre-Rx value <LLN, then <0.8 * pre-Rx or >(ULN -upper limit of normal) ; erythrocytes: <0.75 * pre Rx.
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Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.
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Number of Participants With MAs in Hematology During the ST Study: Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
Time Frame: Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.
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MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point.
The following hematology MA definitions specify the criteria for the data presented.
Neutrophils + bands (absolute): <1.00 * 10^3cells/microlitre (uL); lymphocytes (absolute): <0.75 * 10^3 cells/uL or >7.50 * 10^3 cells/uL; monocytes (absolute): >2.00 * 10^3 cells/uL; basophils (absolute): >0.40 * 10^3 cells/uL; eosinophils (absolute): >0.75 * 10^3 cells/uL.
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Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.
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Number of Participants With MAs in Serum Chemistry During the ST Study: Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Bilirubin (Total), G-Glutamyl Transferase (G-GT) and Blood Urea Nitrogen (BUN)
Time Frame: Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.
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MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point.
The following serum chemistry MA definitions specify MA criteria.
ALP: >2.0 * ULN (if pre-Rx > ULN, then >3 * pre-Rx); AST, ALT: > 3 * ULN (if pre-Rx > ULN, then > 4 * pre-Rx); bilirubin (total): >2 * ULN, or if pre Rx > ULN then >4 * Pre Rx; BUN : >2 * pre Rx; GGT : >2 * ULN, or if pre Rx > ULN then >3 * pre Rx.
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Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.
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Number of Participants With MAs in Serum Chemistry During the ST Study: Creatinine, Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total) and Protein (Total)
Time Frame: Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.
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MAs= laboratory measurements marked as abnormal: creatinine: >1.5 * pre-Rx; sodium (serum):<0.95
* LLN or >1.05 * ULN (if pre-Rx < LLN, then <0.95 * pre-Rx or >1.05 * ULN.
If pre-Rx > ULN, then >0.95 * pre-Rx or < ULN); potassium (serum):<0.9 * LLN or >1.1 * ULN (if pre-Rx < LLN, then <0.9 * pre-Rx or > ULN; chloride (serum),protein (total):<0.9 * LLN or >1.1 8 ULN (if pre-Rx < LLN, then <0.9 * pre-Rx or > ULN.
If pre-Rx > ULN, then >1.1 * pre-Rx or < LLN); calcium (total): <0.8 * LLN or >1.2 * ULN (if pre-Rx < LLN, then <0.9 * pre-Rx or > ULN.
If pre-Rx > ULN, then >0.75 * pre-Rx or < ULN).
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Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.
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Number of Participants With MAs in Serum Chemistry During the ST Study: Glucose (Fasting Serum), Albumin, Glucose (Serum), Phosphorous (Inorganic) and Uric Acid
Time Frame: Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.
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MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point.
The following serum chemistry MA definitions specify MA criteria.
Glucose (fasting serum): <0.8 * LLN or >1.5 ULN (if pre-Rx <LLN, then <2.0 * pre-Rx or >ULN; albumin: <0.9 * LLN (if pre-Rx < LLN, then <0.75 * pre-Rx); uric acid: >1.5 * ULN (if pre-Rx > ULN, then >2.0 * pre-Rx); phosphorous (inorganic):<0.75
* LLN or >1.25 * ULN (if pre-Rx < ULN, then <0.67 * pre-Rx or < ULN.
If pre-Rx > ULN, then >1.33 * re-Rx or < LLN); glucose (serum): <65 mg/dL or >220 mg/dL.
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Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.
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Number of Participants With MAs in Urinalysis During the ST Study: Protein, Glucose, Blood, Leukocyte Esterase, Red Blood Cells (RBC) and White Blood Cells (WBC)
Time Frame: Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.
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MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point.
The following definitions specify the criteria for MAs in urinalysis: protein, glucose, blood, leukocyte esterase, RBC, WBC: >= 2+ (or, if value >= 4, or if pre-Rx value = 0 or 0.5, then >= 2x or if pre-Rx value =1, then >= 3, or if pre-Rx = 2 or 3, then >= 4).
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Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.
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Number of Participants With Anti-nuclear Antibody (ANA) Category at Day 113 of the ST Study
Time Frame: Day 113.
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ANA status was categorized as negative or positive corresponding to the following dilutions: less than 1:160 and greater than equal to 1:160.
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Day 113.
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Number of Participants With Anti-double Stranded DNA (dsDNA) Category at Day 113 of the ST Study
Time Frame: Day 113.
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Anti-dsDNA antibody status was categorized as negative or positive based upon assay-specific numeric cut-off values.
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Day 113.
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Number of Participants With Clinically Meaningful Vital Signs During the ST Study
Time Frame: At screening and on days 1,15,29,43, 57, 85 and 113.
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Vital signs measurements (including seated blood pressure, heart rate and temperature) were recorded.
The investigator used his/her clinical judgment to decide whether or not abnormalities in vital signs/physical examination were clinically meaningful.
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At screening and on days 1,15,29,43, 57, 85 and 113.
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Minimum Plasma Concentration (Cmin) at Each Visit During the 4 Month Treatment Period of the ST Study
Time Frame: Days 1, 15, 29, 43, 57, 85 and 113.
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Cmin serum abatacept concentration was obtained directly from the concentration-time data.
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Days 1, 15, 29, 43, 57, 85 and 113.
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Number of Participants With Abatacept Induced Antibody Responses Over Time During the LTE Study (ECL Method) - All Treated Participants in LTE Study
Time Frame: Days 197, 281, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541, 1625, 1709, 1821, 1989, days post dose: 28, 56, 85, 168
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The Meso-Scale Discovery (MSD) electrochemiluminescence (ECL) assay method is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum.
It is more sensitive and has a higher drug tolerance than ELISA method.
For the anti-abatacept antibody ECL (MSD) assay, a sample was considered seropositive if it had a titer of 10 or greater and if immunodepletion was observed with abatacept, or abatacept and CTLA4-T.
Those responses that were not positive in the initial screen or were not confirmed to be positive based on immunodepletion were reported as seronegative and were assigned a value of < 10.
Antibody responses included CTLA4 and possibly immune globulin (IG), IG and/or junction region.
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Days 197, 281, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541, 1625, 1709, 1821, 1989, days post dose: 28, 56, 85, 168
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Change From Baseline in DAS28-CRP Score in the LTE Study - All Treated Participants in LTE Study
Time Frame: Baseline, Day 113, Day 1345
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DAS28-CRP is a continuous variable which is a composite of 4 variables: the number of tender joints out of 28, the number of swollen joints out of 28, C-reactive protein (CRP) in milligrams/Liter (mg/L) and subject assessment of disease activity measure on a VAS of 100mm.
DAS 28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.36 * ln(CRP+1) + 0.014 * VAS + 0.96.
Baseline was Day 1 of the ST Study; Day 113 was the end of the ST Study.
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Baseline, Day 113, Day 1345
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Number of Participants With Clinically Meaningful Improvement From Baseline in the LTE Study - All Treated Participants in LTE Study
Time Frame: Baseline, Day 113, Day 1345
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A clinically meaningful improvement is defined as a greater than or equal to 1.2 reduction in DAS28-CRP score from baseline.
Baseline was Day 1 of the ST Study.
Day 113 was the end of the ST Study.
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Baseline, Day 113, Day 1345
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Number of Participants in DAS28-CRP Remission and Number of Participants With Low Disease Activity (LDA) in the LTE Study - All Treated Participants in the LTE
Time Frame: Day 113, Day 1345
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DAS28-CRP remission was defined as DAS28-CRP less than 2.6 and LDA was defined as DAS28-CRP less than, equal to 3.2.
End of ST Study was Day 113.
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Day 113, Day 1345
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Change From Baseline in HAQ-DI in the LTE Study - All Treated Participants in LTE Study
Time Frame: Baseline, Day 113, Day 1345
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HAQ-DI takes into account participant's use of aids or devices or assistance in scoring algorithm for a disability category.
The questionnaire includes 20 questions assessing physical function 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 indicate greater dysfunction.
The score is calculated by summing worst scores in each domain and dividing by the number of domains answered.
Baseline was Day 1 in the ST Study and Day 113 was the last day of the ST Study.
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Baseline, Day 113, Day 1345
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Number of Participants With HAQ Responses in the LTE Study - All Treated Participants in the LTE STudy
Time Frame: Baseline, Day 113, Day 1345
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HAQ response was defined as an improvement of at least 0.3 units from baseline in the HAQ Disability Index (HAQ DI).
Baseline was Day 1 of the ST Study and Day 113 was the last day of the ST Study.
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Baseline, Day 113, Day 1345
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Number of Participants With Negative Status for RF up to 7 Days After Last Dose of Abatacept in the LTE Period - All Treated Participants in LTE Study
Time Frame: Continuously from start of LTE period up to 7 days post the last dose
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RF is an autoantibody that is usually present in the serum of people with rheumatoid arthritis.
The cut-point value for seroconversion was 15 IU/mL (>= 15 IU/mL resulted in a positive result).
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Continuously from start of LTE period up to 7 days post the last dose
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Change From Baseline in DAS28-CRP Score and Physical Function (HAQ-DI) Score in the LTE Study - Abatacept Monotherapy Subgroup
Time Frame: Baseline, Day 113, Day 1345
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Abatacept Monotherapy Subgroup consisted of participants who received SC abatacept and did not receive MTX in the ST and LTE Studies.
DAS28-CRP: continuous variable which is a composite of 4 variables:number of tender joints out of 28, number of swollen joints out of 28, C-reactive protein (CRP) in mg/L and self assessment of disease activity measure on a VAS of 100mm.
DAS 28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.36 * ln(CRP+1) + 0.014 * VAS + 0.96.
HAQ-DI includes 20 questions assessing physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities on a 4-point scale: 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty and 3 = unable to do.
Higher scores indicate greater dysfunction.
The score sums worst scores in each domain and divides by the number of domains answered.
Baseline was Day 1 of Short Term Study.
Day 113 was the last day of the Short Term Study.
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Baseline, Day 113, Day 1345
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Number of Participants in DAS 28-CRP Remission and Low Disease Activity (LDA) in the LTE Study - Abatacept Monotherapy Subgroup
Time Frame: Day 113, Day 1345
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Remission was defined as DAS 28-CRP < 2.6 and LDA was defined as DAS 28-CRP <= 3.2.
End of ST Study was Day 113.
Abatacept Monotherapy Subgroup was defined as those participants who received as at least 1 dose of abatacept and did not receive MTX in the ST and LTE Studies.
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Day 113, Day 1345
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Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs), or Discontinued Due to AEs and/or SAEs During the LTE Period - All Treated Participants in LTE Study
Time Frame: Continuously from start of LTE Study up to 56 days post the last dose
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AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug.
SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose.
Drug-related AEs/SAEs are those events with a relationship to the study therapy of certain; probable; possible; or missing.
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Continuously from start of LTE Study up to 56 days post the last dose
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Number of Participants With AEs of Special Interest During the LTE Study - All Treated Participants in LTE Study
Time Frame: Continuously from start of LTE Study up to 56 days post the last dose
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An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug).
For this study, AEs of particular importance were associated with the use of immunomodulatory agents: infections, autoimmune disorders, malignancies, and injection reaction AEs (systemic AEs occurring within 24 hours of SC injection and local injection site reactions) were recorded.
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Continuously from start of LTE Study up to 56 days post the last dose
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Number of Participants With Marked Abnormalities (MAs) in Hematology During the LTE Period - All Treated Participants in LTE Study
Time Frame: Continuously from start of LTE Study up to 56 days post the last dose
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MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point.
The following hematology MA definitions specify the criteria for the data presented.
Hemoglobin: >3 g/dL decrease from pre-treatment (pre Rx); hematocrit: <0.75 * pre-Rx value; platelet count: <0.67 * (LLN -lower limit of normal) (or, if pre-Rx value <LLN, then <0.5 * pre-Rx value and <100,000/mm^3); leukocytes: <0.75 * LLN or >1.25 * ULN (or, if pre-Rx value <LLN, then <0.8 * pre-Rx or >(ULN -upper limit of normal) ; erythrocytes: <0.75 * pre Rx.
Neutrophils + bands (absolute): <1.00 * 10^3cells/microlitre (uL); lymphocytes (absolute): <0.75 * 10^3 cells/uL or >7.50 * 10^3 cells/uL; monocytes (absolute): >2.00 * 10^3 cells/uL; basophils (absolute): >0.40 * 10^3 cells/uL; eosinophils (absolute): >0.75 * 10^3 cells/uL.
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Continuously from start of LTE Study up to 56 days post the last dose
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Number of Participants With MAs in Serum Chemistry (Liver and Kidney Function) During the LTE Period - All Treated Participants in LTE Study
Time Frame: Continuously from start of LTE Study up to 56 days post the last dose
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MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point.
Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Bilirubin (Total), G-Glutamyl Transferase (G-GT), Blood Urea Nitrogen (BUN) and Creatinine MA criteria: ALP: >2.0 * ULN (if pre-Rx > ULN, then >3 * pre-Rx); AST, ALT: > 3 * ULN (if pre-Rx > ULN, then > 4 * pre-Rx); bilirubin (total): >2 * ULN, or if pre Rx > ULN then >4 * Pre Rx; BUN : >2 * pre Rx; GGT : >2 * ULN, or if pre Rx > ULN then >3 * pre Rx; creatinine: >1.5 * pre-Rx.
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Continuously from start of LTE Study up to 56 days post the last dose
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Number of Participants With MAs in Serum Chemistry (Electrolytes, Glucose, Protein, and Metabolite) During the LTE Period - All Treated Participants in LTE Study
Time Frame: Continuously from start of LTE Study up to 56 days post the last dose
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Sodium (serum):<0.95 * LLN or >1.05 * ULN (if pre-Rx < LLN, then <0.95 * pre-Rx or >1.05 * ULN.
If pre-Rx > ULN, then >0.95 * pre-Rx or < ULN); potassium (serum):<0.9 * LLN or >1.1 * ULN (if pre-Rx < LLN, then <0.9 * pre-Rx or > ULN; chloride (serum),protein (total):<0.9 * LLN or >1.1 8 ULN (if pre-Rx < LLN, then <0.9 * pre-Rx or > ULN.
If pre-Rx > ULN, then >1.1 * pre-Rx or < LLN); calcium (total): <0.8 * LLN or >1.2 * ULN (if pre-Rx < LLN, then <0.9 * pre-Rx or > ULN.
If pre-Rx > ULN, then >0.75 * pre-Rx or < ULN); phosphorous (inorganic):<0.75
* LLN or >1.25 * ULN (if pre-Rx < ULN, then <0.67 * pre-Rx or < ULN.
If pre-Rx > ULN, then >1.33 * re-Rx or <LLN); glucose (serum): <65 mg/dL or >220 mg/dL; Glucose (fasting serum): <0.8 * LLN or >1.5 ULN (if pre-Rx <LLN, then <2.0 * pre-Rx or >ULN; albumin: <0.9 * LLN (if pre-Rx < LLN, then <0.75 * pre-Rx); uric acid: >1.5 * ULN (if pre-Rx > ULN, then >2.0 * pre-Rx).
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Continuously from start of LTE Study up to 56 days post the last dose
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Number of Participants With MAs in Urinalysis During the LTE Period: Protein, Glucose, Blood, Leukocyte Esterase, Red Blood Cells (RBC) and White Blood Cells (WBC) - All Treated Participants in LTE Study
Time Frame: Continuously from start of LTE Study up to 56 days post the last dose
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MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point.
The following definitions specify the criteria for MAs in urinalysis: protein, glucose, blood, leukocyte esterase, RBC, WBC: >= 2+ (or, if value >= 4, or if pre-Rx value = 0 or 0.5, then >= 2x or if pre-Rx value =1, then >= 3, or if pre-Rx = 2 or 3, then >= 4).
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Continuously from start of LTE Study up to 56 days post the last dose
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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.
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
December 1, 2007
Primary Completion (Actual)
December 1, 2008
Study Completion (Actual)
February 1, 2014
Study Registration Dates
First Submitted
October 19, 2007
First Submitted That Met QC Criteria
October 19, 2007
First Posted (Estimate)
October 22, 2007
Study Record Updates
Last Update Posted (Estimate)
March 23, 2015
Last Update Submitted That Met QC Criteria
March 13, 2015
Last Verified
March 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis
- Arthritis, Rheumatoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Immune Checkpoint Inhibitors
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Methotrexate
- Abatacept
Other Study ID Numbers
- IM101-173
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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