Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Remission and Joint Damage Progression in Early 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: NCT00122382
Recruitment Status : Completed
First Posted : July 22, 2005
Results First Posted : July 13, 2010
Last Update Posted : November 16, 2010
Sponsor:
Information provided by:
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: Abatacept
Drug: placebo
Drug: methotrexate
Enrollment 1052
Recruitment Details  
Pre-assignment Details 1052 participants were enrolled, 541 were not randomized (2 for adverse events, 32 subjects withdrew consent, 1 pregnancy, 6 lost to follow-up, 470 no longer met study criteria, 30 for other reasons).
Arm/Group Title Abatacept (ABA) + Methotrexate (MTX) (Double-Blind) Placebo (PLA) + Methotrexate (MTX) (Double-Blind) ABA + MTX (Open-Label)
Hide Arm/Group Description ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12 (end of double blind period). Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX) titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12 (end of double blind period). Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with weekly oral MTX were administered every 28 days from Month 12 to Month 24 (open-label period).
Period Title: Double-Blind Study
Started 256 [1] 255 [1] 0
Treated 256 253 0
Completed 232 227 0
Not Completed 24 28 0
Reason Not Completed
Adverse Event             9             11             0
Death             2             2             0
Lack of Efficacy             0             8             0
Lost to Follow-up             2             1             0
Pregnancy             2             0             0
Subject No Longer Meets Study Criteria             1             0             0
Withdrawal of Consent             7             3             0
Protocol Violation             1             0             0
Methotrexate Discontinued             0             1             0
Randomized but not treated             0             2             0
[1]
participants randomized
Period Title: Open-Label Study
Started 0 0 459
Completed 0 0 433
Not Completed 0 0 26
Reason Not Completed
Adverse Event             0             0             11
Death             0             0             2
Lack of Efficacy             0             0             3
Lost to Follow-up             0             0             3
Pregnancy             0             0             2
Poor/Non-Compliance             0             0             1
Withdrawal of Consent             0             0             4
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind) Total
Hide Arm/Group Description ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12. Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12. Total of all reporting groups
Overall Number of Baseline Participants 256 253 509
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 256 participants 253 participants 509 participants
50.1  (12.4) 49.7  (13.0) 49.9  (12.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 256 participants 253 participants 509 participants
Female
196
  76.6%
199
  78.7%
395
  77.6%
Male
60
  23.4%
54
  21.3%
114
  22.4%
Anti-Cyclic Citrullinated Peptide 2 (CCP2) Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 256 participants 253 participants 509 participants
unknown 2 0 2
positive 236 217 453
negative 18 36 54
[1]
Measure Description: Anti-CCP2 antibodies are autoantibodies that react with citrullinated proteins, are frequent in Rheumatoid Arthritis and are associated with erosive disease. > 5 units/mL is a positive result.
Duration of Rheumatoid Arthritis (RA) Disease  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 256 participants 253 participants 509 participants
</= 6 months 167 157 324
> 6 months - 12 months 36 34 70
> 12 months 53 62 115
Rheumatoid Factor (RF) Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 256 participants 253 participants 509 participants
unknown 1 1 2
positive 246 245 491
negative 9 7 16
[1]
Measure Description: Rheumatoid Factor 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).
Disease Activity Scale 28 (DAS 28) C-reactive Protein (CRP)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 256 participants 253 participants 509 participants
6.3  (1.0) 6.2  (1.0) 6.3  (1.0)
[1]
Measure Description: DAS 28-CRP=continuous composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28, CRP in milligrams/Liter (mg/L), and subject assessment of disease activity measured on a Visual Analogue Scale (VAS) of 100 millimeters (mm). Current disease activity is presented on a scale of 0 to 10, with a score above 5.1=high disease activity and below 3.2=low disease activity. VAS=a measurement instrument for characteristics that range across a continuum of values. Range is 1 to 100; a lower value signifies improvement. 1 participant in Placebo group was not evaluated.
Duration of RA  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 256 participants 253 participants 509 participants
6.2  (7.5) 6.7  (7.1) 6.5  (7.3)
Erosion Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 256 participants 253 participants 509 participants
5.4  (6.1) 4.8  (5.4) 5.1  (5.8)
[1]
Measure Description: To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The erosion score range is 0 (no radiographic damage) to 145 (worst possible radiographic damage). Higher scores indicated more damage. 3 participants in the abatacept group were not included in the measure.
Health Assessment Questionnaire - Disability Index (HAQ-DI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 256 participants 253 participants 509 participants
1.7  (0.7) 1.7  (0.7) 1.7  (0.7)
[1]
Measure Description: HAQ-DI=self-reported measure of physical function calculated as a mean of 8 category scores: Dressing/Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, Activities. Each category score is calculated as the maximum of the scores for the questions within the category. HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute HAQ score. Changes to lower scores=improvement in physical function. 2 participants in the abatacept and placebo groups were not evaluated.
Joint Space Narrowing (JSN) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 256 participants 253 participants 509 participants
2.1  (4.2) 1.9  (4.0) 2.0  (4.1)
[1]
Measure Description: To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The joint space narrowing score range is 0 (no radiographic damage) to 145 (worst possible radiographic damage). Higher scores indicated more damage. 3 participants in the abatacept group were not included in the measure.
Physician Global Assessment per Visual Analogue Scale (VAS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 256 participants 253 participants 509 participants
67.1  (18.2) 65.7  (18.9) 66.4  (18.5)
[1]
Measure Description: Physician Global Assessment is measured by VAS (100 mm). A Visual Analogue Scale (VAS) is a measurement instrument for characteristics that range across a continuum of values. Range is 1-100; a lower score indicates a better Physician Assessment of Global Health. 1 participant in the abatacept group was not evaluated for this measure.
Subject Global Assessment per VAS   [1] 
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 256 participants 253 participants 509 participants
65.8  (21.8) 63.7  (24.0) 64.8  (22.9)
[1]
Measure Description: Subject Global Assessment is measured by VAS (100 mm). A Visual Analogue Scale (VAS) is a measurement instrument for characteristics that range across a continuum of values. Range is 1-100; a lower score indicates a better Subject Assessment of Global Health. 1 participant in the Placebo group was not evaluated for this measure.
Subject Pain Assessment per VAS   [1] 
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 256 participants 253 participants 509 participants
66.6  (22.5) 67.1  (22.6) 66.8  (22.5)
[1]
Measure Description: Subject Pain Assessment measured by VAS (100 mm). A Visual Analogue Scale (VAS) is a measurement instrument for characteristics that range across a continuum of values. Range is 1-100; a lower value signifies a better subject pain assessment. 1 participant in the Placebo group was not evaluated for this measure.
Swollen Joints   [1] 
Mean (Standard Deviation)
Unit of measure:  Number of swollen joints
Number Analyzed 256 participants 253 participants 509 participants
22.9  (11.3) 21.9  (10.1) 22.4  (10.8)
[1]
Measure Description: Total number of joints analyzed=66
Tender Joints   [1] 
Mean (Standard Deviation)
Unit of measure:  Number of tender joints
Number Analyzed 256 participants 253 participants 509 participants
31.3  (14.8) 30.8  (14.0) 31.0  (14.4)
[1]
Measure Description: Total number of joints analyzed=68
Total Genant-modified Sharp score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 256 participants 253 participants 509 participants
7.5  (9.7) 6.7  (8.8) 7.1  (9.2)
[1]
Measure Description: To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage. 3 participants in the abatacept group were not included in the measure.
1.Primary Outcome
Title Number of Participants in DAS 28 C-reactive Protein (CRP) Remission at Month 12
Hide Description Number of participants who achieved remission at Month 12 of treatment, as defined by a Disease Activity Score (DAS) 28-CRP score of <2.6. DAS 28-CRP is a continuous measure, a composite of 4 variables: number of tender joints out of 28 joints, number of swollen joints out of 28 joints, CRP (in mg/L), and subject assessment of disease activity measure on a Visual Analogue Scale (VAS) of 100 millimeters (mm). The DAS28 scale=0 (best) to 10 (worst), indicating the current activity of the rheumatoid arthritis. A DAS28 >5.1 = high disease activity; <=3.2 = low disease activity; <2.6 = remission.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat = all randomized and treated subjects. Those with missing data post-discontinuation were considered non-responders.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
Overall Number of Participants Analyzed 256 253
Measure Type: Number
Unit of Measure: participants
106 59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX (Double-Blind), PLA + MTX (Double-Blind)
Comments Estimated Difference between ABA and PLA is the estimated difference between ABA and PLA in the proportion of subjects achieving DAS28-CRP remission.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Total score was tested only if there was statistical significance in remission rate. For each test, the nominal type I error rate is set at 5%; this sequential testing procedure preserves the overall type I error rate at 5%.
Method Chi-squared, Continuity-Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference between ABA and PLA
Estimated Value 18.1
Confidence Interval (2-Sided) 95%
9.6 to 26.6
Estimation Comments [Not Specified]
2.Primary Outcome
Title Mean Change From Baseline in Radiographic Total Score to Month 12
Hide Description To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and joint space narrowing (JSN). The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Time Frame Baseline, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was intent-to-treat. Because the analysis was change from baseline, only those with baseline and post-baseline were included. Linear extrapolation imputation was applied.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
Overall Number of Participants Analyzed 242 242
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Mean 7.50  (9.52) 6.67  (8.71)
Mean Change from Baseline 0.63  (1.74) 1.06  (2.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX (Double-Blind), PLA + MTX (Double-Blind)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.040
Comments Total score was tested only if there was statistical significance in remission rate. For each test, the nominal type I error rate is set at 5%; this sequential testing procedure preserves the overall type I error rate at 5%.
Method non-parametric ANCOVA
Comments [Not Specified]
3.Primary Outcome
Title Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Related AE/SAE=Certain, Probable, Possible, or Missing. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Time Frame Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose of ABA in the open-label period were included in the safety analyses.
Arm/Group Title ABA + MTX (Open-Label)
Hide Arm/Group Description:
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period).
Overall Number of Participants Analyzed 459
Measure Type: Number
Unit of Measure: participants
AEs 345
Related AEs 128
SAEs 29
Related SAEs 10
Discontinuations due to AEs 11
Discontinuations due to SAEs 4
Deaths 2
4.Primary Outcome
Title Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Hide Description SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Time Frame Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose of ABA in the open-label period were included in the safety analyses.
Arm/Group Title ABA + MTX (Open Label)
Hide Arm/Group Description:
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period).
Overall Number of Participants Analyzed 459
Measure Type: Number
Unit of Measure: participants
Any SAE 29
Infections and infestations 8
Gastrointestinal disorders 4
Nervous system disorders 4
Cardiac disorders 3
Hepatobiliary disorders 3
Eye disorders 2
Musculoskeletal and connective tissue disorders 2
Vascular disorders 2
Immune System Disorders 1
Injury, Poisoning, and Procedural Complications 1
Investigations 1
Metabolism and Nutrition Disorders 1
Renal and Urinary Disorders 1
Respiratory, Thoracic, and Mediastinal Disorders 1
5.Primary Outcome
Title Number of Participants With SAEs With an Outcome of Death During the Open-label Period
Hide Description Any untoward medical occurrence (SAE) that resulted in death
Time Frame Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose of ABA in the open-label period were included in the safety analyses.
Arm/Group Title ABA + MTX (Open-Label)
Hide Arm/Group Description:
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period).
Overall Number of Participants Analyzed 459
Measure Type: Number
Unit of Measure: participants
Pneumonia 1
Pneumonia/septic shock 1
6.Primary Outcome
Title Incidence Rates of Autoimmune Disorders in ABA-Treated Participants
Hide Description The incidence rates of autoimmune disorders are defined as the (number of patients experiencing the event/exposure within the period)*100 and are expressed in 100 person-years. Subjects experiencing the event had their exposure censored at the time of the 1st event.
Time Frame Double Blind Period (+56 days post last dose in double-blind period or start of open-label period, whichever came first). Open-label period (56 days post last dose in the open-label period or start of maintenance sub-study, whichever came first).
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose of abatacept. Double-blind (DB) period: all treated in DB period; Open-label (OL) Period: all treated in OL period.
Arm/Group Title ABA + MTX (Double-Blind) ABA + MTX (Open-Label)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period).
Overall Number of Participants Analyzed 256 459
Measure Type: Number
Unit of Measure: Number of participants/100 patient-years
2.47 1.30
7.Primary Outcome
Title Incidence Rates of Infections and Infestations of Adverse Events in ABA-Treated Participants
Hide Description The incidence rates of infections and infestations are defined as the (number of patients experiencing the event /exposure within the period)*100 and are expressed in 100 person-years. Subjects experiencing the event had their exposure censored at the time of the 1st event.
Time Frame Double Blind Period (+56 days post last dose in double-blind period or start of the open-label period, whichever came first). Open-label period (56 days post last dose in open-label period or start of maintenance sub-study, whichever came first).
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose of abatacept. Double-blind (DB) period: all treated in DB period; Open-label (OL) Period: all treated in OL period.
Arm/Group Title ABA + MTX (Double-Blind) ABA + MTX (Open-Label)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period).
Overall Number of Participants Analyzed 256 459
Measure Type: Number
Unit of Measure: Number of patients/100 patient-years
78.37 66.68
8.Primary Outcome
Title Incidence Rates of Malignant Neoplasm Adverse Events in ABA-Treated Participants
Hide Description The incidence rates of malignant neoplasms are defined as the (number of patients experiencing the event /exposure within the period)*100 and are expressed in 100 person-years. Subjects experiencing the event had their exposure censored at the time of the 1st event.
Time Frame Double Blind Period (+56 days post last dose in double-blind period or start of the open-label period, whichever came first). Open-label period (56 days post last dose in open-label period or start of maintenance sub-study, whichever came first).
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose of abatacept. Double-blind (DB) period: all treated in DB period; Open-label (OL) Period: all treated in OL period.
Arm/Group Title ABA + MTX (Double-Blind) ABA + MTX (Open-Label)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period).
Overall Number of Participants Analyzed 256 459
Measure Type: Number
Unit of Measure: number of patients/100 patient-years
0.81 0
9.Primary Outcome
Title Number of Participants With a Serious Acute-Infusional AE of Anaphylactic Shock During Open-Label Period
Hide Description There were 107 Prespecified, acute-infusional SAEs (occurring within 1 hour after the start of study drug infusion) pre-specified in the protocol; anaphylactic shock was the only one occuring in this study.
Time Frame Open-Label Period (Month 12 to Month 24)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated during the Open-Label period.
Arm/Group Title ABA + MTX (Open-label)
Hide Arm/Group Description:
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period).
Overall Number of Participants Analyzed 459
Measure Type: Number
Unit of Measure: Participants
1
10.Primary Outcome
Title Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Hide Description Number of subjects with high liver function and kinedy tests: alkaline phosphatase (ALP) >2x upper limit of normal (ULN) or if pretreatment (PRE-RX) >ULN then >3x PRE-RX; aspartate aminotransferase (AST) >3x ULN or if PRE-RX >ULN then >4x PRE-RX; alanine aminotransferase (ALT) >3x ULN or if PRE-RX >ULN then >4x PRE-RX; g-glutamyl transferase (GGT)>2x ULN or if PRE-RX >ULN then >3x PRE-RX; total bilirubin >2x ULN or if PRE-RX >ULN then >4x PRE-RX; blood urea nitrogen >2x PRE-RX; creatinine >1.5x PRE-RX.
Time Frame Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated participants in the Open-label Period; n=number of participants evaluated for this measure.
Arm/Group Title ABA + MTX (Open-Label)
Hide Arm/Group Description:
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period).
Overall Number of Participants Analyzed 459
Measure Type: Number
Unit of Measure: participants
ALP (n=459) 2
AST (n=459) 10
ALT (n=459) 24
GGT (n=459) 15
Total Bilirubin (n=459) 0
Blood Urea Nitrogen (n=459) 13
Creatinine (n=457) 81
11.Primary Outcome
Title Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Hide Description Marked abnormalities in hemoglobin >3 g/dL decrease from PRE-RX; hematocrit <0.75x PRE-RX; erythrocytes <0.75x PRE-RX; platelet count <0.67x lower limit of normal (LLN) or >1.5x ULN or if PRE-RX <LLN then <0.5x PRE-RX and <100,000/mm3; leukocytes <0.75x LLN or >1.25x ULN or if PRE-RX <LLN then <0.8x PRE-RX or >ULN if PRE-RX >ULN then >1.2x PRE-RX or <LLN; neutrophils if value <1.00 x10^3 c/uL; lymphocytes if value <.750 x10^3 c/uL or if value >7.50 x10^3 c/uL; monocytes if value >2000/MM3; basophils if value >400/mm3; eosinophils if value >.750 x10^3 c/uL
Time Frame Continuously from start of open-label period up to 56 days post the last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated during the open-label period; n= number of participants evaluated for this measure.
Arm/Group Title ABA + MTX (Open-Label)
Hide Arm/Group Description:
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period).
Overall Number of Participants Analyzed 459
Measure Type: Number
Unit of Measure: participants
Low Hemoglobin (n=458) 9
Low Hematocrit (n=458) 5
Low Erythrocyte (n=458) 8
Low Platelet Count (n=455) 1
High Platelet Count (n=455) 1
Low Leukocytes (n=458) 14
High Leukocytes (n=458) 12
Low Neutrophils + Bands (absolute) (n=459) 6
Low Lymphocytes (absolute) (n=459) 39
High Lymphocytes (absolute) (n=459) 1
High Monocytes (absolute) (n=459) 0
High Basophils (absolute) (n=459) 2
High Eosinophils (absolute) (n=459) 19
12.Secondary Outcome
Title Number of Participants With American College of Rheumatology (ACR) 50 Response at Month 12
Hide Description ACR 50 response was defined as a 50% improvement from baseline to Month 12 in tender and swollen joint counts and 50% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function), and 1 acute phase reactant value [ie, CRP].
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-Treat=All randomized and treated; all missing data subsequent to discontinuation are considered non-responders.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
Overall Number of Participants Analyzed 256 253
Measure Type: Number
Unit of Measure: participants
147 107
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX (Double-Blind), PLA + MTX (Double-Blind)
Comments Estimated Difference between ABA and PLA is the estimated difference between ABA and PLA in the proportion of subjects achieving an ACR 50 response.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value of <0.05: probability for testing the difference between ABA and PLA.
Method Chi-squared, Continuity-Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference between ABA and PLA
Estimated Value 15.1
Confidence Interval (2-Sided) 95%
6.0 to 24.2
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Number of Participants With Major Clinical Response (MCR) at Month 12
Hide Description MCR was defined as 6 months of consecutive ACR 70 response at Month 12. ACR 70, the American College of Rheumatology (ACR) definition of 70% improvement was based on a 70% improvement (compared to baseline values) in tender and swollen joint counts and 70% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function, and 1 acute phase reactant value [ie, CRP]).
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-Treat=All randomized and treated; all missing data subsequent to discontinuation are considered non-responders.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
Overall Number of Participants Analyzed 256 253
Measure Type: Number
Unit of Measure: participants
70 30
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX (Double-Blind), PLA + MTX (Double-Blind)
Comments Estimated Difference between ABA and PLA is the estimated difference between ABA and PLA in the proportion of subjects achieving MCR.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value of <0.05: probability for testing the difference between ABA and PLA.
Method Chi-squared, Continuity-Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference between ABA and PLA
Estimated Value 15.5
Confidence Interval (2-Sided) 95%
8.2 to 22.8
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Adjusted Mean Change From Baseline in DAS-28-CRP Score to Month 12
Hide Description DAS 28-CRP is a continuous variable that is a composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, CRP in milligrams/Liter (mg/L), and subject assessment of disease activity measure on a Visual Analogue Scale (VAS) of 100 millimeters (mm). The DAS28 scale=0 to 10, indicating the current activity of the rheumatoid arthritis. A DAS28 >5.1=high disease activity; <3.2=low disease activity; <2.6=remission. Change from Baseline=Post-baseline - Baseline value; Adjusted for baseline value.
Time Frame Baseline, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward (LOCF) Intent to Treat population = all randomized and treated. As change from baseline analysis, only those with baseline and post-baseline included.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
Overall Number of Participants Analyzed 253 251
Mean (Standard Error)
Unit of Measure: units in a scale
-3.22  (0.09) -2.49  (0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX (Double-Blind), PLA + MTX (Double-Blind)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value of <0.05: probability for testing the difference between ABA and PLA.
Method ANCOVA
Comments Adjustment based on ANCOVA model with treatment as factor and baseline value as covariate.
Method of Estimation Estimation Parameter Estimate of/Adjusted Difference
Estimated Value -0.73
Confidence Interval (2-Sided) 95%
-0.98 to -0.48
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 12
Hide Description Physical function was evaluated using the HAQ-disability index (HAQ-DI), a questionnaire with 20 questions assessing 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; 3 = unable to do. The 8 category scores are averaged into an overall HAQ-DI score on a scale from 0 (no disability) to 3 (completely disabled). Higher scores indicate greater dysfunction. HAQ response=improvement of at least 0.3 units from baseline.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-Treat=All randomized and treated; all missing data subsequent to discontinuation are considered non-responders.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
Overall Number of Participants Analyzed 256 253
Measure Type: Number
Unit of Measure: participants
184 157
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX (Double-Blind), PLA + MTX (Double-Blind)
Comments Estimated Difference between ABA and PLA is the estimated difference between ABA and PLA in the proportion of subjects achieving HAQ response.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments p-value of <0.05: probability for testing the difference between ABA and PLA.
Method Chi-squared, Continuity-Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference between ABA and PLA
Estimated Value 9.8
Confidence Interval (2-Sided) 95%
1.3 to 18.4
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Adjusted Mean Change in Short Form 36 (SF-36) From Baseline to Month 12
Hide Description The SF-36 covers 8 health dimensions: 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from 0 to 100, with a higher score indicating better quality of life. Two summary scores (physical and mental component summaries) were produced taking a weighted linear combination of the 8 individual subscales. Change from Baseline=Post-baseline - Baseline value; adjusted for baseline value.
Time Frame Baseline, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward (LOCF) Intent to Treat population = all randomized and treated. As change from baseline analysis, only those with baseline and post-baseline included.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
Overall Number of Participants Analyzed 254 249
Mean (Standard Error)
Unit of Measure: units on a scale
Physical Component Summary (PCS) Score 11.68  (0.62) 9.18  (0.63)
Mental Component Summary (MCS) Score 8.15  (0.64) 6.34  (0.64)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX (Double-Blind), PLA + MTX (Double-Blind)
Comments PCS Adjusted Mean Change from Baseline to Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments p-value of <0.05: probability for testing the difference between ABA and PLA.
Method ANCOVA
Comments Adjustment based on ANCOVA model with treatment as factor and baseline value as covariate.
Method of Estimation Estimation Parameter Estimate of/Adjusted Difference
Estimated Value 2.50
Confidence Interval (2-Sided) 95%
0.77 to 4.23
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ABA + MTX (Double-Blind), PLA + MTX (Double-Blind)
Comments MCS Adjusted Mean Change from Baseline to Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments p-value of <0.05: probability for testing the difference between ABA and PLA.
Method ANCOVA
Comments Adjustment based on ANCOVA model with treatment as factor and baseline value as covariate.
Method of Estimation Estimation Parameter Estimate of/Adjusted Difference
Estimated Value 1.81
Confidence Interval (2-Sided) 95%
0.03 to 3.60
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Mean Change From Baseline in Radiographic Erosion and Joint Space Narrowing (JSN) Scores to Month 12
Hide Description To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The erosion score range is 0 (no radiographic damage) to 145 (worst possible radiographic damage). The joint space narrowing score range is 0 (no radiographic damage) to 145 (worst possible radiographic damage). Higher scores indicated more damage. Change from baseline = Post-baseline - Baseline value
Time Frame Baseline, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-Treat - linear extrapolation imputation. Analysis of change from baseline restricts subjects included in to the analysis to those with baseline and post-baseline.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
Overall Number of Participants Analyzed 242 242
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Mean Erosion Score 5.48  (6.15) 4.81  (5.46)
Mean Change from Baseline in Erosion Score 0.50  (1.39) 0.89  (2.24)
Baseline Mean JSN Score 2.03  (3.99) 1.86  (3.95)
Mean Change from Baseline in JSN Score 0.13  (0.53) 0.17  (0.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX (Double-Blind), PLA + MTX (Double-Blind)
Comments comparison of change in erosion scores between abatacept and placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments P-value of <0.05: probability for comparison of change in radiographic scores between abatacept and placebo.
Method Nonparametric ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ABA + MTX (Double-Blind), PLA + MTX (Double-Blind)
Comments comparison of change in JSN scores between abatacept and placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.353
Comments P-value of <0.05: probability for comparison of change in radiographic scores between abatacept and placebo.
Method Nonparametric ANCOVA
Comments [Not Specified]
18.Secondary Outcome
Title Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses in the Double-blind Period as Analyzed by Enzyme-linked-immunosorbent Serologic Assay (ELISA)
Hide Description Serum samples were analyzed by ELISA to detect antibodies against the whole molecule (both CTLA4 and Ig [anti-abatacept antibody]) or solely to CTLA4 (anti-CTLA4-T antibody). Reported as titer, the reciprocal of the sample dilution which yielded a signal equivalent to the statistically set cut point for the assay. For the anti-abatacept assay, minimum required dilution is 400-fold, therefore seronegative samples are those < lowest reportable titer (<400). For the anti-CTLA4-T assay, minimum required dilution is 25-fold, therefore seronegative samples are those < lowest reportable titer (<25).
Time Frame includes data up to approximately 85 days past the last dose of the double-blind period or start of the open-label period, whichever occurred first.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants in the double-blind period who were evaluated for anti-abatacept or anti-CTLA4-T responses
Arm/Group Title ABA+ MTX On-treatment ABA + MTX Post-discontinuation
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Overall Number of Participants Analyzed 249 13
Measure Type: Number
Unit of Measure: Participants
Anti-abatacept Responses 3 0
Anti-CTLA4-T Responses 1 1
19.Secondary Outcome
Title Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses During the Open-Label Period (From Month 12 to Month 24) as Analyzed by ELISA
Hide Description Serum samples were analyzed by ELISA to detect antibodies against the whole molecule (both CTLA4 and Ig [anti-abatacept antibody]) or solely to CTLA4 (anti-CTLA4-T antibody). Reported as titer, the reciprocal of the sample dilution which yielded a signal equivalent to the statistically set cut point for the assay. For the anti-abatacept assay, minimum required dilution is 400-fold, therefore seronegative samples are those < lowest reportable titer (<400). For the anti-CTLA4-T assay, minimum required dilution is 25-fold, therefore seronegative samples are those < lowest reportable titer (<25).
Time Frame Includes open-label data up to approximately 85 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants in the open-label period were evaluated for anti-abatacept or anti-CTLA4-T responses
Arm/Group Title Anti-Abatacept Antibody Response Anti-CTLA4-T Antibody Response
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 451 456
Measure Type: Number
Unit of Measure: participants
13 16
20.Secondary Outcome
Title Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 24
Hide Description Physical function was evaluated using the HAQ-disability index (HAQ-DI), a questionnaire with 20 questions assessing 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; 3 = unable to do. The 8 category scores are averaged into an overall HAQ-DI score on a scale from 0 (no disability) to 3 (completely disabled). Higher scores indicate greater dysfunction. HAQ response=improvement of at least 0.3 units from baseline.
Time Frame Baseline, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the Open-label period. Treatment groups represent treatment received in the Double Blind Period.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period). The groups are determined by treatment status in the double blind period to observe efficacy differences.
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period). The groups are determined by treatment status in the double blind period to observe efficacy differences.
Overall Number of Participants Analyzed 232 227
Measure Type: Number
Unit of Measure: participants
189 178
21.Secondary Outcome
Title Mean Change From Baseline in Radiographic Total, Erosion and JSN Scores to Month 24
Hide Description To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage. Change from baseline = Postbaseline - baseline value.
Time Frame Baseline, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the open-label period. Because the analysis was change from baseline, only those with baseline and post-baseline were included. Linear extrapolation imputation was applied. Treatment groups represent treatment received in the double-blind period.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period). The groups are determined by treatment status in the double blind period to observe efficacy differences.
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period). The groups are determined by treatment status in the double blind period to observe efficacy differences.
Overall Number of Participants Analyzed 213 192
Mean (Standard Deviation)
Unit of Measure: units on a scale
Erosion Score Baseline Mean 5.91  (6.48) 5.49  (5.85)
Erosion Score Mean Change from Baseline 0.59  (2.31) 1.40  (3.08)
JSN Score Baseline Mean 1.83  (3.82) 1.75  (3.92)
JSN Score Mean Change from Baseline 0.25  (1.03) 0.34  (0.99)
Total Score Baseline Mean 7.73  (9.50) 7.24  (8.89)
Total Score Mean Change from Baseline 0.84  (3.22) 1.75  (3.59)
22.Secondary Outcome
Title Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) From Baseline at Month 24
Hide Description Participants with no radiographic progression (defined as change in score <=0 or <=0.5), from baseline to Month 24. To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Time Frame Baseline, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the open-label period. Treatment groups represent treatment received in the double-blind period.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period). The groups are determined by treatment status in the double blind period to observe efficacy differences.
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week was administered every 28 days from Month 12 to Month 24 (open-label period). The groups are determined by treatment status in the double blind period to observe efficacy differences.
Overall Number of Participants Analyzed 213 192
Measure Type: Number
Unit of Measure: Participants
Change from Baseline <= 0 in Erosion Score 125 92
Change from Baseline <= 0.5 in Erosion Score 144 114
Change from Baseline <= 0 in JSN Score 175 150
Change from Baseline <= 0.5 in JSN Score 190 166
Change from Baseline <= 0 in Total Score 121 84
Change from Baseline <= 0.5 in Total Score 139 107
23.Secondary Outcome
Title Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) at Month 24 in Participants Without Progression at Month 12
Hide Description Participants with no radiographic progression ((defined as change in score <=0 or <=0.5), sustained from Month 12 and Month 24. To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Time Frame Month 12, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All treated participants in the open-label period. (Treatment groups represent treatment received in the double-blind period.) n=the number of subjects with observed data included in the analysis.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
Overall Number of Participants Analyzed 232 227
Measure Type: Number
Unit of Measure: Participants
Erosion Score Sustained <=0 (n=125; n=100) 116 87
Erosion Score Sustained <=0.5 (n=145; n=114) 135 107
JSN Score Sustained <=0 (n=180; n=165) 169 150
JSN Score Sustained <=0.5 (n=192; n=177) 185 163
Total Score sustained <=0 (n=123; n=97) 112 81
Total Score sustained <=0.5 (n=144; n=112) 131 101
24.Secondary Outcome
Title Mean Difference Observed in Change From Baseline to Month 12 and Between Month 12 and Month 24 in Radiographic Scores (Total Score)
Hide Description Mean difference observed in change from baseline to Month 12 and between Month 12 and Month 24 in radiographic scores (Total Score). To assess joint damage, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Time Frame Baseline, Month 12, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis includes all treated participants in the open-label period originally randomized to abatacept. Analysis includes all participants with observed assessments collected at Baseline (Day 1), Day 365 (Month 12), and Day 729 (Month 24)
Arm/Group Title Year 1 Change Year 2 Change
Hide Arm/Group Description:
Year 1 Change = Day 365 - Day 1
Year 2 Change = Day 729 (Month 24) - Day 365 (Month 12)
Overall Number of Participants Analyzed 207 207
Mean (Standard Error)
Unit of Measure: units on a scale
0.66  (0.13) 0.18  (0.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Year 1 Change, Year 2 Change
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method signed rank test
Comments [Not Specified]
25.Secondary Outcome
Title Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Related AE/SAE=Certain, Probable, Possible, or Missing. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Time Frame Includes data up to 56 days post the last dose in the double-blind period or start of the open-label period, whichever occurred first.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the Double-Blind period
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
Overall Number of Participants Analyzed 256 253
Measure Type: Number
Unit of Measure: participants
Deaths 2 4
SAEs 20 20
Related SAEs 5 6
Discontinued due to SAEs 3 3
AEs 217 211
Related AEs 98 114
Discontinued due to AEs 8 11
26.Secondary Outcome
Title Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Hide Description Number of participants with laboratory values (hematology, liver and kidney functions, electrolytes, glucose tests, protein tests, metabolite tests, and urine chemistry tests) considered markedly abnormal according to prespecified protocol criteria
Time Frame Includes data up to 56 days post the last dose in the double-blind period or start of the open-label period, whichever occurred first.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated in the DB period. n=Number of participants evaluated for this measure.
Arm/Group Title ABA + MTX (Double-Blind) PLA + MTX (Double-Blind)
Hide Arm/Group Description:
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
Overall Number of Participants Analyzed 256 253
Measure Type: Number
Unit of Measure: participants
Low Hemoglobin (n=254; n=251) 3 3
Low Hematocrit (n=254; n=250) 1 2
Low Erythrocytes (n=254; n=250) 1 4
Low Platelet Count (n=252; n=250) 0 1
High Platelet Count (n=252; n=250) 1 3
Low Leukocytes (n=254; n=251) 5 11
High Leukocytes (n=254; n=251) 5 14
Low Neutrophils + Bands (absolute) (n=254; n=252) 2 5
Low Lymphocytes (absolute) (n=254; n=252) 13 29
High Lymphocytes (absolute) (n=254; n=252) 0 0
High Monocytes (absolute) (n=254; n=252) 1 1
High Basophils (absolute) (n=254; n=252) 0 0
High Eosinophils (absolute) (n=254; n=252) 7 13
High Alkaline Phosphatase (n=254; n=253) 1 0
High Aspartate Aminotransferase (n=254; n=253) 7 14
High Alanine Aminotransferase (n=254; n=253) 15 21
G-Glutamyl Transferase (n=254; n=253) 11 9
High Bilirubin, Total (n=254; n=253) 0 2
High Blood Urea Nitrogen (n=254; n=253) 9 10
High Creatinine (n=254; n=251) 33 32
Low Sodium, Serum (n=254; n=253) 0 1
High Sodium, Serum (n=254; n=253) 2 0
Low Potassium, Serum (n=254; n=251) 6 3
High Potassium, Serum (n=254; n=251) 3 2
Low Chloride, Serum (n=254; n=253) 0 0
High Chloride, Serum (n=254; n=253) 1 0
Low Calcium, Total (n=254; n=253) 0 0
High Calcium, Total (n=254; n=253) 0 0
Low Phosphorus, Inorganic (n=254; n=251) 1 2
High Phosphorus, Inorganic (n=254; n=251) 3 3
Low Glucose, Serum (n=254; n=253) 22 24
High Glucose, Serum (n=254; n=253) 10 13
Low Protein, Total (n=254; n=253) 2 0
High Protein, Total (n=254; n=253) 0 1
Low Albumin (n=254; n=253) 2 5
High Protein, Urine (n=252; n=250) 6 3
High Glucose, Urine (n=252; n=250) 4 6
High Blood, Urine (n=252; n=250) 30 22
High Leukocyte Esterase (n=87; n=88) 13 13
High Red Blood Cells, Urine (n=92; n=103) 30 25
High White Blood Cells, Urine (n=94; n=105) 38 42
High Uric Acid (n=254; n=253) 1 1
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Abatacept Placebo
Hide Arm/Group Description ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12. Placebo (Dextrose 5% Water for Injection U.S.P. [D5W] or Normal Saline [NS] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
All-Cause Mortality
Abatacept Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Abatacept Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   20/256 (7.81%)   20/253 (7.91%) 
Cardiac disorders     
PERICARDIAL EFFUSION  1  1/256 (0.39%)  0/253 (0.00%) 
MYOCARDIAL INFARCTION  1  1/256 (0.39%)  1/253 (0.40%) 
CARDIAC FAILURE CONGESTIVE  1  0/256 (0.00%)  1/253 (0.40%) 
Gastrointestinal disorders     
DIARRHOEA  1  1/256 (0.39%)  0/253 (0.00%) 
ABDOMINAL PAIN  1  0/256 (0.00%)  1/253 (0.40%) 
INGUINAL HERNIA  1  1/256 (0.39%)  0/253 (0.00%) 
GASTROINTESTINAL HAEMORRHAGE  1  1/256 (0.39%)  0/253 (0.00%) 
General disorders     
SUDDEN DEATH  1  1/256 (0.39%)  0/253 (0.00%) 
MULTI-ORGAN FAILURE  1  0/256 (0.00%)  1/253 (0.40%) 
INFUSION RELATED REACTION  1  1/256 (0.39%)  0/253 (0.00%) 
Hepatobiliary disorders     
CHOLECYSTITIS  1  0/256 (0.00%)  1/253 (0.40%) 
ACUTE HEPATIC FAILURE  1  0/256 (0.00%)  1/253 (0.40%) 
Immune system disorders     
ANAPHYLACTIC REACTION  1  0/256 (0.00%)  1/253 (0.40%) 
Infections and infestations     
PNEUMONIA  1  1/256 (0.39%)  3/253 (1.19%) 
CELLULITIS  1  1/256 (0.39%)  0/253 (0.00%) 
GASTROENTERITIS  1  1/256 (0.39%)  1/253 (0.40%) 
BREAST CELLULITIS  1  0/256 (0.00%)  1/253 (0.40%) 
STAPHYLOCOCCAL INFECTION  1  0/256 (0.00%)  1/253 (0.40%) 
LUNG INFECTION PSEUDOMONAL  1  1/256 (0.39%)  0/253 (0.00%) 
POSTOPERATIVE WOUND INFECTION  1  1/256 (0.39%)  0/253 (0.00%) 
Injury, poisoning and procedural complications     
FALL  1  1/256 (0.39%)  0/253 (0.00%) 
TIBIA FRACTURE  1  1/256 (0.39%)  0/253 (0.00%) 
ROAD TRAFFIC ACCIDENT  1  1/256 (0.39%)  0/253 (0.00%) 
SPINAL COMPRESSION FRACTURE  1  1/256 (0.39%)  0/253 (0.00%) 
Investigations     
INTERNATIONAL NORMALISED RATIO INCREASED  1  1/256 (0.39%)  0/253 (0.00%) 
Metabolism and nutrition disorders     
DEHYDRATION  1  0/256 (0.00%)  1/253 (0.40%) 
Musculoskeletal and connective tissue disorders     
ARTHRITIS  1  0/256 (0.00%)  1/253 (0.40%) 
OSTEOARTHRITIS  1  0/256 (0.00%)  1/253 (0.40%) 
MUSCULOSKELETAL PAIN  1  0/256 (0.00%)  1/253 (0.40%) 
RHEUMATOID ARTHRITIS  1  1/256 (0.39%)  1/253 (0.40%) 
SPINAL OSTEOARTHRITIS  1  0/256 (0.00%)  1/253 (0.40%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
LIPOMA  1  1/256 (0.39%)  0/253 (0.00%) 
NEOPLASM SKIN  1  1/256 (0.39%)  0/253 (0.00%) 
PANCREATIC CARCINOMA  1  1/256 (0.39%)  0/253 (0.00%) 
Nervous system disorders     
INTRACRANIAL PRESSURE INCREASED  1  0/256 (0.00%)  1/253 (0.40%) 
Psychiatric disorders     
DEPRESSION  1  2/256 (0.78%)  0/253 (0.00%) 
Renal and urinary disorders     
URETHRAL STENOSIS  1  0/256 (0.00%)  1/253 (0.40%) 
Reproductive system and breast disorders     
CERVICAL DYSPLASIA  1  0/256 (0.00%)  1/253 (0.40%) 
Respiratory, thoracic and mediastinal disorders     
PLEURISY  1  0/256 (0.00%)  1/253 (0.40%) 
PLEURAL EFFUSION  1  1/256 (0.39%)  0/253 (0.00%) 
PULMONARY EMBOLISM  1  0/256 (0.00%)  1/253 (0.40%) 
RESPIRATORY FAILURE  1  0/256 (0.00%)  1/253 (0.40%) 
INTERSTITIAL LUNG DISEASE  1  1/256 (0.39%)  0/253 (0.00%) 
CRYPTOGENIC ORGANISING PNEUMONIA  1  1/256 (0.39%)  0/253 (0.00%) 
Vascular disorders     
HYPOTENSION  1  1/256 (0.39%)  0/253 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Abatacept Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   150/256 (58.59%)   155/253 (61.26%) 
Gastrointestinal disorders     
NAUSEA  1  26/256 (10.16%)  41/253 (16.21%) 
DIARRHOEA  1  17/256 (6.64%)  24/253 (9.49%) 
DYSPEPSIA  1  11/256 (4.30%)  14/253 (5.53%) 
ABDOMINAL PAIN UPPER  1  9/256 (3.52%)  15/253 (5.93%) 
Infections and infestations     
INFLUENZA  1  19/256 (7.42%)  23/253 (9.09%) 
BRONCHITIS  1  18/256 (7.03%)  12/253 (4.74%) 
NASOPHARYNGITIS  1  21/256 (8.20%)  26/253 (10.28%) 
URINARY TRACT INFECTION  1  17/256 (6.64%)  22/253 (8.70%) 
UPPER RESPIRATORY TRACT INFECTION  1  26/256 (10.16%)  26/253 (10.28%) 
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  16/256 (6.25%)  13/253 (5.14%) 
Musculoskeletal and connective tissue disorders     
BACK PAIN  1  13/256 (5.08%)  14/253 (5.53%) 
Nervous system disorders     
HEADACHE  1  30/256 (11.72%)  23/253 (9.09%) 
DIZZINESS  1  19/256 (7.42%)  13/253 (5.14%) 
Respiratory, thoracic and mediastinal disorders     
COUGH  1  21/256 (8.20%)  16/253 (6.32%) 
Vascular disorders     
HYPERTENSION  1  17/256 (6.64%)  14/253 (5.53%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00122382     History of Changes
Other Study ID Numbers: IM101-023
First Submitted: July 19, 2005
First Posted: July 22, 2005
Results First Submitted: May 3, 2010
Results First Posted: July 13, 2010
Last Update Posted: November 16, 2010