Study of Abatacept (BMS-188667) in Subjects With Active Rheumatoid Arthritis on Background Non-biologic DMARDS (Disease Modifying Antirheumatic Drugs) Who Have an Inadequate Response to Anti-TNF Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00124982
First received: June 30, 2005
Last updated: February 23, 2012
Last verified: February 2012
Results First Received: February 18, 2011  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Drug: Abatacept
Drug: Non-biologic Disease Modifying Anti-Rheumatic Drug (DMARD)
Drug: Anti-Tumor Necrosing Factor (TNF) Therapy

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 1286 participants enrolled in this study, 240 were not treated.

Reporting Groups
  Description
Short Term (ST) Abatacept (ABA)-Previous User In participants who had previously used Tumor Necrosis Factor (TNF)-agonists, open-label abatacept was administered on Days 1, 15, and 29 and then once a month thereafter on a background of non-biologic Disease Modifying Anti-Rheumatic Drug (DMARD)s. Participants weighing < 60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram of open-label abatacept by intravenous (IV) infusion.
ST-Current User In participants currently using Tumor Necrosis Factor (TNF)-agonists, open-label abatacept was administered on Days 1, 15, and 29 and then once a month thereafter on a background of non-biologic Disease Modifying Anti-Rheumatic Drug (DMARD)s. Participants weighing < 60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram of open-label abatacept by intravenous (IV) infusion.
Long-term ABA Participants continued to receive the same 10 mg/kg weight-tiered dose of abatacept that they received in the initial short-term period.

Participant Flow for 2 periods

Period 1:   Short-term Period
    Short Term (ST) Abatacept (ABA)-Previous User     ST-Current User     Long-term ABA  
STARTED     449     597     0  
COMPLETED     377     483     0  
NOT COMPLETED     72     114     0  
Death                 1                 1                 0  
Adverse Event                 17                 22                 0  
Lack of Efficacy                 32                 73                 0  
Lost to Follow-up                 8                 5                 0  
Withdrawal of Consent                 7                 9                 0  
Poor/Non-compliance                 3                 1                 0  
No Longer Meets Study Criteria                 1                 2                 0  
Participant Decision                 1                 0                 0  
Participant Chose Own Doctor                 0                 1                 0  
Investigator Decision-No Specific AE                 1                 0                 0  
Participant Had Lymphopenia                 1                 0                 0  

Period 2:   Long-term Period
    Short Term (ST) Abatacept (ABA)-Previous User     ST-Current User     Long-term ABA  
STARTED     0     0     530 [1]
COMPLETED     0     0     441  
NOT COMPLETED     0     0     89  
Death                 0                 0                 1  
Adverse Event                 0                 0                 17  
Lack of Efficacy                 0                 0                 46  
Lost to Follow-up                 0                 0                 4  
Withdrawal by Subject                 0                 0                 16  
Pregnancy                 0                 0                 1  
Poor/Non-compliance                 0                 0                 2  
Administrative Reason by Sponsor                 0                 0                 1  
Neurologist Recommendation                 0                 0                 1  
[1] A large number did not continue due to a rollover from study drug to commercially available drug.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
ST Abatacept (ABA)-Previous User In participants who had previously used Tumor Necrosis Factor (TNF)-agonists, open-label abatacept was administered on Days 1, 15, and 29 and then once a month thereafter on a background of non-biologic Disease Modifying Anti-Rheumatic Drug (DMARD)s. Participants weighing < 60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram of open-label abatacept by intravenous (IV) infusion.
ST ABA-Current User In participants currently using Tumor Necrosis Factor (TNF)-agonists, open-label abatacept was administered on Days 1, 15, and 29 and then once a month thereafter on a background of non-biologic Disease Modifying Anti-Rheumatic Drug (DMARD)s. Participants weighing < 60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram of open-label abatacept by intravenous (IV) infusion.
Total Total of all reporting groups

Baseline Measures
    ST Abatacept (ABA)-Previous User     ST ABA-Current User     Total  
Number of Participants  
[units: participants]
  449     597     1046  
Age  
[units: years]
Mean ± Standard Deviation
  56.1  ± 12.5     53.2  ± 12.3     54.4  ± 12.4  
Gender  
[units: participants]
     
Female     359     490     849  
Male     90     107     197  
Number of Tender Joints [1]
[units: tender joints]
Mean ± Standard Deviation
  17.8  ± 5.9     17.8  ± 6.1     17.8  ± 6.0  
Number of Swollen Joints [2]
[units: swollen joints]
Mean ± Standard Deviation
  13.9  ± 5.6     13.5  ± 5.4     13.6  ± 5.5  
Physical Function, Health Assessment Questionnaire Disability Index (HAQ-DI) [3]
[units: units on a scale]
Mean ± Standard Deviation
  1.7  ± 0.6     1.7  ± 0.6     1.7  ± 0.6  
hs-C-Reactive Protein (hs-CRP) Serum Levels [4]
[units: mg/dL]
Mean ± Standard Deviation
  2.2  ± 3.0     2.1  ± 3.0     2.1  ± 3.0  
Disease Activity Score (DAS) 28 (Using CRP Levels) [5]
[units: units on a scale]
Mean ± Standard Deviation
  6.2  ± 0.7     6.2  ± 0.7     6.2  ± 0.7  
Rheumatoid Factor (RF) Status [6]
[units: participants]
     
Negative     138     215     353  
Positive     292     349     641  
Data Not Available     19     33     52  
[1] The mean number of tender joints was evaluated based on the number of tender joints in a standard 68 joint count.
[2] The mean number of swollen joints was evaluated based on the number of swollen joints in a standard 66 joint count.
[3] The HAQ-DI includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The domain 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. HAQ-DI= sum of worst scores in each domain divided by the number of domains answered. HAQ-DI ranges from a minimum of 0 (no difficulty) to a maximum overall score of 3(unable to do).
[4] hs-CRP is a acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA). Levels of hs-CRP can be used to determine DAS28.
[5] The DAS28 (CRP) is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, serum CRP level, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response= decrease in DAS28 score of >1.2 from baseline.
[6] Rheumatoid factor (RF or RhF) is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Short-term Period: Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuations, AEs, Related AEs, or AEs Leading to Discontinuations   [ Time Frame: Days 1-169 ]

2.  Primary:   Short-term Period: Number of Participants With AEs of Special Interest   [ Time Frame: Days 1-169 ]

3.  Primary:   Short-term Period: Number of Participants With Hematology Laboratories Meeting Marked Abnormality (MA) Criteria   [ Time Frame: Days 1-169 ]

4.  Primary:   Short-term Period: Number of Participants With Liver and Kidney Function Laboratories Meeting MA Criteria   [ Time Frame: Days 1-169 ]

5.  Primary:   Short-term Period: Number of Participants With Electrolyte Laboratories Meeting MA Criteria   [ Time Frame: Days 1-169 ]

6.  Primary:   Short-term Period: Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting MA Criteria   [ Time Frame: Days 1-169 ]

7.  Primary:   Short-term Period: Mean Change From Baseline in Systolic and Diastolic Blood Pressure   [ Time Frame: Day 1 (Baseline) -Day 169 ]

8.  Primary:   Short-term Period: Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA)   [ Time Frame: Days 1-169 ]

9.  Primary:   Long-term Period: Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuations, AEs, Related AEs, or AEs Leading to Discontinuations   [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ]

10.  Primary:   Long-term Period: Number of Participants With AEs of Special Interest   [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ]

11.  Primary:   Long-term Period: Number of Participants With Hematology Laboratories Meeting Marked Abnormality (MA) Criteria   [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ]

12.  Primary:   Long-term Period: Number of Participants With Liver and Kidney Function Laboratories Meeting MA Criteria   [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ]

13.  Primary:   Long-term Period: Number of Participants With Electrolyte Laboratories Meeting MA Criteria   [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ]

14.  Primary:   Long-term Period: Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting MA Criteria   [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ]

15.  Primary:   Long-term Period: Change From Baseline in Hemoglobin (HGB), Total Protein, and Albumin Over Time   [ Time Frame: BL, Day 365, Day 729 ]

16.  Primary:   Long-term Period: Change From Baseline in Hematocrit Over Time   [ Time Frame: BL, Day 365, Day 729 ]

17.  Primary:   Long-term Period: Change From Baseline in Erythrocytes Over Time   [ Time Frame: BL, Day 365, Day 729 ]

18.  Primary:   Long-term Period: Change From Baseline in Platelets (PLT) Over Time   [ Time Frame: BL, Day 365, Day 729 ]

19.  Primary:   Long-term Period: Change From Baseline in White Blood Cells Over Time   [ Time Frame: BL, Day 365, Day 729 ]

20.  Primary:   Long-term Period: Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and G-Glutamyl Transferase (GGT) Over Time   [ Time Frame: BL, Day 365, Day 729 ]

21.  Primary:   Long-term Period: Change From Baseline in Bilirubin, Blood Urea Nitrogen (BUN), Creatinine, Calcium (Ca), Phosphorus (P), Serum Glucose (Glu), and Uric Acid Over Time   [ Time Frame: BL, Day 365, Day 729 ]

22.  Primary:   LT; Change From Baseline in Sodium (Na), Potassium (K), Chloride (Cl) Over Time   [ Time Frame: BL, Day 365, Day 729 ]

23.  Primary:   Long-term Period: Mean Sitting Systolic Blood Pressure (SBP) Over Time   [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ]

24.  Primary:   Long-term Period: Mean Sitting Diastolic Blood Pressure (DBP) Over Time   [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ]

25.  Primary:   Long-term Period: Mean Heart Rate (HR) Over Time   [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ]

26.  Primary:   Long-term Period: Mean Temperature (T) Over Time   [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ]

27.  Secondary:   Short-term Period: Number of Participants With Clinically Meaningful Improvement (CMI) in Disease Activity Score (DAS 28), Low Disease Activity (LDAS), or Remission at Day 169   [ Time Frame: BL, Day 169 ]

28.  Secondary:   Short-term Period: Mean Time-matched Baseline (Day 0) DAS 28 and DAS 28 for Post-Baseline Visits Through 6 Month Open-Label   [ Time Frame: BL (Day 0), Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169 ]

29.  Secondary:   Short-term Period: Mean Time-matched Change From Baseline (Day 0) in DAS 28 Through 6 Month Open-Label   [ Time Frame: BL (Day 0), Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169 ]

30.  Secondary:   Short-term Period: Mean Change From Baseline to Day 169 in High Sensitivity C-Reactive Protein (Hs-CRP)   [ Time Frame: BL, Day 169 ]

31.  Secondary:   Short-term Period: Mean Change From Baseline to Day 169 in Rheumatoid Factor (RF)   [ Time Frame: BL, Day 169 ]

32.  Secondary:   Short-term Period: Mean Change From Baseline to Day 169 in the Health Assessment Questionnaire Disability Index (HAQ-DI)   [ Time Frame: BL, Day 169 ]

33.  Secondary:   Short-term Period: Number of Participants Achieving a Clinically Meaningful HAQ Response   [ Time Frame: BL, Day 169 ]

34.  Secondary:   Short-term Period: Mean Baseline Short Form 36 (SF-36) Quality of Life Physical Component Summary (PCS), Mental Component Summary (MCS), and SF-36 Individual Component Scores   [ Time Frame: BL ]

35.  Secondary:   Short-term Period: Mean Change From Baseline to Day 169 in SF-36 PCS, MCS, and SF-36 Individual Component Scores   [ Time Frame: BL, Day 169 ]

36.  Secondary:   Short-term Period: Mean Baseline Fatigue Visual Analog Scale (VAS)   [ Time Frame: BL ]

37.  Secondary:   Short-term Period: Mean Change From Baseline to Day 169 in Fatigue Visual Analog Scale (VAS)   [ Time Frame: BL, Day 169 ]

38.  Secondary:   Long-term Period: Number of Participants With Clinically Meaningful Improvement in DAS 28, Low Disease Activity, or Remission Over Time   [ Time Frame: BL, Days 365, 449, 533, 617, 729, 813 ]

39.  Secondary:   Long-term Period: Mean Time-matched Baseline (Day 0) DAS 28 and DAS 28 for Post-Baseline Visits Over the Long Term   [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ]

40.  Secondary:   Long-term Period: Mean Time-matched Change From Baseline (Day 0) in DAS 28 Over The Long Term   [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ]

41.  Secondary:   Long-term Period: Mean Time-matched Baseline (Day 0) Number of Tender Joints and Number of Tender Joints for Post-Baseline Visits Over the Long Term   [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ]

42.  Secondary:   Long-term Period: Mean Time-matched Change From Baseline (Day 0) in Number of Tender Joints Over the Long Term   [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ]

43.  Secondary:   Long-term Period: Mean Time-matched Baseline (Day 0) Number of Swollen Joints And Post-Baseline Number of Swollen Joints Over the Long Term   [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ]

44.  Secondary:   Long-term Period: Mean Time-Matched Change From Baseline (Day 0) in Number of Swollen Joints Over the Long Term   [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ]

45.  Secondary:   Long-term Period: Mean Time-matched Baseline (Day 0) Hs-CRP Levels and Hs-CRP Levels for Post-Baseline Over the Long Term   [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ]

46.  Secondary:   Long-term Period: Mean Time-matched Change From Baseline (Day 0) in Hs-CRP Level Over the Long Term   [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ]

47.  Secondary:   Long-term Period: Mean Time-matched Baseline (Day 0) Visual Analog Scale (VAS) and VAS for Post-Baseline Visits Over the Long Term   [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ]

48.  Secondary:   Long-term Period: Mean Time-matched Change From Baseline (Day 0) in VAS Over the Long Term   [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ]

49.  Secondary:   Long-term Period: Mean Time-matched Baseline (Day 0) HAQ-DI and HAQ-DI Component Scores For Participant Cohorts at Each Corresponding Post-baseline Visit Over the Long Term   [ Time Frame: BL (Day 0) ]

50.  Secondary:   Long-term Period: Mean HAQ-DI and HAQ-DI Component Scores For Participant Cohorts at Post-baseline Visits Over the Long Term   [ Time Frame: Days 365, 449, 533, 617, 729, 813 ]

51.  Secondary:   Long-term Period: Mean Time-matched Change From Baseline (Day 0) in HAQ-DI and HAQ-DI Components For Participant Cohorts at Each Corresponding Post-baseline Visit Over the Long Term   [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ]

52.  Secondary:   Long-term Period: Number of Participants Achieving Clinically Meaningful HAQ Response Over Time   [ Time Frame: BL, Days 365, 449, 533, 617, 729, 813 ]

53.  Secondary:   Long-term Period: Mean Time-matched Baseline (Day 0) SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participant Cohorts at Each Corresponding Post-baseline Visit Over the Long Term   [ Time Frame: BL (Day 0) ]

54.  Secondary:   Long-term Period: Mean SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participant Cohorts at Each Post-baseline Visits Over the Long Term   [ Time Frame: Days 365 and 729 ]

55.  Secondary:   Long-term Period: Mean Time-matched Change From Baseline (Day 0) in SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participant Cohorts at Each Corresponding Post-baseline Visit Over the Long Term   [ Time Frame: BL (Day 0), Days 365, 729 ]

56.  Secondary:   LT; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA   [ Time Frame: Days 1-813 ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


Publications:
Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00124982     History of Changes
Other Study ID Numbers: IM101-064
Study First Received: June 30, 2005
Results First Received: February 18, 2011
Last Updated: February 23, 2012
Health Authority: United States: Food and Drug Administration