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Phase IIIB Subcutaneous Missed Dose Study

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: NCT00533897
Recruitment Status : Completed
First Posted : September 24, 2007
Results First Posted : June 3, 2011
Last Update Posted : April 23, 2015
Sponsor:
Information provided by (Responsible Party):
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
Enrollment 270
Recruitment Details Participants with Rheumatoid Arthritis (American College of Rheumatology Class I, II or III) were enrolled. Study initiated November 2007. Short Term (ST) results and some long term extension (LTE) results up to a database lock in 2010 were released earlier. Study concluded February 2014. Final LTE results are now included.
Pre-assignment Details 270 participants enrolled; 167 were treated in the Short Term (ST) study. 103 were not treated (10 withdrew consent, 2 lost to follow-up, 91 no longer met study criteria). ST study included 3 Periods: Lead-In (LI), Doubleblind Withdrawal (DBW), and Reintroduction (RI).150 participants entered the LTE study.
Arm/Group Title Abatacept (ABA) [Lead-In (LI)] Abatacept (ABA) Double-blind Withdrawal (DBW) Placebo (PLA) Double Blind Withdrawal (DBW) ABA With IV PLA Loading Dose in Re-introduction (RI) Period PLA Switched to ABA With ABA IV Loading Dose in RI Period PLA Switched to ABA With PLA IV Loading Dose in RI Period Long Term Extension Abatacept for LI Period Non-responders Long Term Extension (LTE) Abatacept for Short Term Completers
Hide Arm/Group Description On Day 1 of the 12 week Lead-In (LI), participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78. After receiving ABA in the LI, participants received double blind ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks. After receiving ABA in the LI Period, participants received double blind Placebo SC injections starting on Day 85 and weekly for 12 weeks. After receiving ABA in LI Period, and ABA in DBW Period, participants received a single blinded placebo IV dose on Day 169 and continued with weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg) in the RI Period. After receiving ABA in LI period, and PLA in the DBW Period, participants were randomized to receive a single weight-titered ABA IV loading dose (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) followed by weekly open-label SC ABA injections (fixed dose of 125 mg) in the RI Period. After receiving ABA in the Lead-In, and PLA in the DBW Period, participants were randomized to receive a single Placebo IV loading dose on Day 169 followed by weekly open-label SC ABA injections (fixed dose of 125 mg) in the RI Period. Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve Disease Activity Score 28 (DAS28-CRP) decrease by ≥ 0.6 from Day 1), they directly entered the Long Term Extension (LTE) receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study. Participant’s who successfully completed the Short Term of the study, could enter the LTE on Day 253 and receive weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Period Title: Lead-in (LI) Period 1
Started 167 0 0 0 0 0 0 0
Completed 157 [1] 0 0 0 0 0 0 0
Not Completed 10 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             1             0             0             0             0             0             0             0
Participant Withdrew Consent             2             0             0             0             0             0             0             0
Lost to Follow-up             1             0             0             0             0             0             0             0
Administrative Reason By Sponsor             2             0             0             0             0             0             0             0
Lack of Efficacy             3             0             0             0             0             0             0             0
Missed 2 Consecutive Doses of Study Drug             1             0             0             0             0             0             0             0
[1]
37 participants entered the LTE directly and did not enter the DBW Period nor receive DBW treatment.
Period Title: Double-blind Withdrawal (DBW) Period 2
Started 0 40 80 0 0 0 0 0
Completed 0 39 [1] 77 [2] 0 0 0 0 0
Not Completed 0 1 3 0 0 0 0 0
Reason Not Completed
Lack of Efficacy             0             1             2             0             0             0             0             0
Poor/Non-Compliance             0             0             1             0             0             0             0             0
[1]
One participant discontinued the DBW Period due to Lack of Efficacy to enter the RI Period early
[2]
Two participants discontinued the DBW Period due to Lack of Efficacy to enter the RI Period early
Period Title: Re-introduction (RI) Period 3
Started 0 0 0 40 [1] 35 [1] 44 [1] 0 0
Completed 0 0 0 40 35 42 0 0
Not Completed 0 0 0 0 0 2 0 0
Reason Not Completed
Participant Withdrew Consent             0             0             0             0             0             1             0             0
No Longer Meets Study Criteria             0             0             0             0             0             1             0             0
[1]
1 participant discontinued the DBW Period due to Lack of Efficacy to enter RI Period early
Period Title: Long Term Extension (LTE)
Started 0 0 0 0 0 0 37 [1] 113 [2]
Completed 0 0 0 0 0 0 24 [3] 88 [3]
Not Completed 0 0 0 0 0 0 13 25
Reason Not Completed
Participant Withdrew Consent             0             0             0             0             0             0             2             5
Death             0             0             0             0             0             0             1             3
Lack of Efficacy             0             0             0             0             0             0             5             3
Poor/Non-compliance             0             0             0             0             0             0             1             0
Adverse Event             0             0             0             0             0             0             2             5
Pregnancy             0             0             0             0             0             0             0             2
Lost to Follow-up             0             0             0             0             0             0             1             1
Other             0             0             0             0             0             0             1             6
[1]
37 non-responders in Lead-In entered the LTE directly and didn't participate in DBW or RI Periods.
[2]
117 completed RI but 4 did not enter LTE: 1 lack of efficacy and 3 had their site closed.
[3]
Participant continued until SC ABA was available in respective country or Sponsor ended study.
Arm/Group Title Period 1 Non-Responders Abatacept Received in Period 2 Placebo Received in Period 2 Total
Hide Arm/Group Description Participants received abatacept (ABA) intravenous (IV) loading dose and subcutaneous (SC) injections (fixed dose of 125 mg abatacept) on Day 1 followed by weekly SC injections of ABA up to Day 85 during the Lead-in Period (Period 1). Period 1 non-responders skipped Periods 2 and 3 and entered the long term extension (LTE). Participants received ABA IV loading dose and SC injections (fixed dose of 125 mg abatacept) on Day 1 followed by weekly SC injections of ABA up to Day 85 during the Lead-in Period (Period 1). Period 1 responders continued into Period 2 and were randomized to ABA (Day 85-169). Participants received ABA IV loading dose and SC injections (fixed dose of 125 mg abatacept) on Day 1 followed by weekly SC injections of ABA up to Day 85 during the Lead-in Period (Period 1). Period 1 responders continued into Period 2 and were randomized to Placebo (Day 85-169). Total of all reporting groups
Overall Number of Baseline Participants 37 40 80 157
Hide Baseline Analysis Population Description
All Period 1 Non-responders and Period 2 participants who received at least one dose of abatacept during the study were summarized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 37 participants 40 participants 80 participants 157 participants
53.4  (12.7) 48.9  (14.2) 49.1  (12.8) 49.8  (13.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 40 participants 80 participants 157 participants
Female
30
  81.1%
34
  85.0%
67
  83.8%
131
  83.4%
Male
7
  18.9%
6
  15.0%
13
  16.3%
26
  16.6%
1.Primary Outcome
Title Double-blind Withdrawal (DBW) Period; Percentage of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Antibody Responses by Enzyme-Linked Immunosorbent Assay (ELISA) at Day 169
Hide Description Serum samples from all treated adult participants with active rheumatoid arthritis (RA) were screened for the presence of drug-specific antibodies using an enzyme-linked immunosorbent assay (ELISA). Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Time Frame Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated in the DBW Period with at least 1 immunogenicity result (ELISA) during DBW Period. N=Number of Participants Analyzed, n=number of participants with data for that time point
Arm/Group Title Abatacept in DBW Period Placebo in DBW Period
Hide Arm/Group Description:
Participants received Abatacept (ABA) SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks
Participants received placebo (PLA) SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: percentage of participants
Anti-abatacept (n=37, n=71) 0 1.4
Anti-CTLA4-T (n=38, n=73) 0 8.2
Total (n=38, n=73) 0 9.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept in DBW Period, Placebo in DBW Period
Comments A continuity corrected Chi-square test was used to compare percentage of positive antibody responses of SC placebo vs. SC abatacept (Period II treatment groups) on Day 169. P-value was evaluated at 0.05 significance level (2-sided). 95% confidence interval (CI) for difference (SC PLA - SC ABA) between ABA and PLA in the immunogenicity rates was also calculated. Point estimates of the immunogenicity rates within the two Period II treatment group and the corresponding 95% CIs were also provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.119
Comments There was no adjustment made for multiple comparisons.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter estimate of difference
Estimated Value 9.59
Confidence Interval (2-Sided) 95%
0.83 to 18.34
Estimation Comments [Not Specified]
2.Primary Outcome
Title Re-introduction (RI) Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Day 253, by DBW Period Groups
Hide Description Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Time Frame Day 253 (short term)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated in RI period with at least 1 immunogenicity result (ELISA) during RI period. N=Number of Participants Analyzed, n=number of participants with data for that time point.
Arm/Group Title ABA in DBW Period Placebo in DBW Period
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 79
Measure Type: Number
Unit of Measure: percentage of participants
Anti-abatacept (n=38, n=73) 0 0
Anti-CTLA4-T (n=38, n=73) 2.6 2.7
Total (n=38, n=73) 2.6 2.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA in DBW Period, Placebo in DBW Period
Comments Immunogenicity rates of the Period II treatment groups on Day 253 were analyzed similarly as on Day 169. However, no statistical test was carried out and no p-value was provided. Provided were: point estimates of the immunogenicity rates within the Period II treatment groups and corresponding 95% CIs, and point estimate for the difference in immunogenicity rates between these groups and corresponding 95% CI. There was no adjustment made for multiple comparisons.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimate of Difference
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
-8.21 to 8.43
Estimation Comments [Not Specified]
3.Secondary Outcome
Title RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Day 253, by DBW Period Placebo Group
Hide Description Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Time Frame Day 253 (short term)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated with Placebo in DBW period who were treated in RI period and had at least 1 immunogenicity result (ELISA) during RI period. N=Number of Participants Analyzed, n=number of participants with data for that time point
Arm/Group Title PLA Switched to ABA With ABA IV Loading Dose in RI Period PLA Switched to ABA With PLA IV Loading Dose in RI Period
Hide Arm/Group Description:
On Day 169, participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced in the RI Period.
On Day 169, participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced in the RI Period.
Overall Number of Participants Analyzed 35 44
Measure Type: Number
Unit of Measure: percentage of participants
Anti-abatacept (n=32, n=41) 0 0
Anti-CTLA4-T (n=32, n=41) 0 4.9
Total (n=32, n=41) 0 4.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PLA Switched to ABA With ABA IV Loading Dose in RI Period, PLA Switched to ABA With PLA IV Loading Dose in RI Period
Comments Immunogenicity rates of the Period II treatment groups on Day 253 were analyzed similarly as on Day 169. However, no statistical test was carried out and no p-value was provided. Provided were: point estimates of the immunogenicity rates within the Period II treatment groups and corresponding 95% CIs, and point estimate for the difference in immunogenicity rates between these groups and corresponding 95% CI. There was no adjustment made for multiple comparisons.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimate of Difference
Estimated Value 4.88
Confidence Interval (2-Sided) 95%
-4.50 to 14.25
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Lead-in (LI) Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time
Hide Description Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Time Frame For on-treatment visits: Day 1-Day 85, includes ≤21 Days after last dose or up to 1st dose of DBW Period. For follow-up post visits for participants who discontinued drug in LI: Day 22 after last dose of drug to Day 85 after last dose of drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in LI Period who had at least 1 immunogenicity result (ELISA) during LI period. N=Number of Participants Analyzed, n=number of participants with data for that time point
Arm/Group Title Abatacept in Lead-In Period
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) Abatacept (ABA) dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Measure Type: Number
Unit of Measure: percentage of participants
Overall on TRT visits: anti-ABA (n=162) 1.2
Overall on TRT visits: anti-CTLA4 (n=165) 0
Overall on TRT visits: Total (n=165) 1.2
Overall post visits: anti-ABA (n=3) 0
Overall post visits: anti-CTLA4 (n=3) 0
Overall post visits: Total (n=3) 0
Overall anti-ABA (n=162) 1.2
Overall anti-CTLA4 (n=165) 0
Overall Total (n=165) 1.2
5.Secondary Outcome
Title LI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by Electrochemiluminescence (ECL) Over Time
Hide Description ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNC) Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing or negative.
Time Frame For on-treatment visits: Day 1-Day 85, includes ≤21 Days after last dose or up to 1st dose of DBW Period. For follow-up post visits for participants who discontinued drug in LI: Day 22 after last dose of drug to Day 85 after last dose of drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in Period 1 (Lead-in Period). N=Number of Participants Analyzed, n=number of participants with data for that time point
Arm/Group Title Abatacept in Lead-In Period
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Measure Type: Number
Unit of Measure: percentage of participants
Overall onTRT visits CTLA4 and Possibly Ig, n=165 1.2
Overall onTRT visits Ig and/or JNC region, n=165 0
Overall onTRT visits Total, n=165 1.2
Overall post visits CTLA4 and possibly Ig, n=3 0
Overall post visits Ig and/or JNC region, n=3 0
Overall post visits: Total, n=3 0
Overall CTLA4 and possibly Ig, n=165 1.2
Overall Ig and/or JNC region, n=165 0
Overall Total (n=165) 1.2
6.Secondary Outcome
Title DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time
Hide Description Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody. Samples were obtained during treatment (TRT) visits.
Time Frame Days 86-169, includes ≤21 Days after last dose or up to 1st dose of RI Period
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in DBW period with at least 1 immunogenicity result (ELISA) during DBW period. N=Number of Participants Analyzed, n=number of participants with data for that time point.
Arm/Group Title Abatacept in DBW Period Placebo in DBW Period
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: percentage of participants
Overall on TRT visits: anti-ABA, n=39,78 0 1.3
Overall on TRT visits anti-CTLA4, n=40,80 0 7.5
Overall on TRT visits: Total, n=40,80 0 8.8
7.Secondary Outcome
Title DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Post Visits
Hide Description Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Time Frame Day 22 after last dose of drug to Day 85 after last dose of drug
Hide Outcome Measure Data
Hide Analysis Population Description
These data were not summarized since there were no participants at any post visits.
Arm/Group Title ABA in DBW Period PLA in DBW Period
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL Over Time
Hide Description ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNC) Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing or negative.
Time Frame Days 86-169, includes ≤21 Days after last dose or up to 1st dose of RI Period
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in DBW period with at least 1 immunogenicity result (ECL) during DBW period. N=Number of Participants Analyzed, n=number of participants with data for that time point
Arm/Group Title ABA in DBW Period PLA in DBW Period
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: percentage of participants
Overall onTRT visits CTLA4 and Possibly Ig,n=40,80 0 6.3
Overall onTRT visits Ig and/or JNC region, n=40,80 0 3.8
Overall on TRT visits: Total Abs, n=40,80 0 10
9.Secondary Outcome
Title DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL At Post Visits
Hide Description ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNC) Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing or negative.
Time Frame Day 22 after last dose of drug to Day 85 after last dose of drug
Hide Outcome Measure Data
Hide Analysis Population Description
These data were not summarized since there were no participants at any post visits
Arm/Group Title ABA in DBW Period PLA in DBW Period
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time by DBW Treatment Group
Hide Description Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Time Frame For on-treatment visits: Days 170-253, includes ≤21 Days after last dose or up to 1st dose of LTE Period. For follow-up post visits for participants who discontinued drug in RI: Day 22 after last dose of drug to Day 85 after last dose of drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in RI period with at least 1 immunogenicity result (ELISA) during RI period N=Number of Participants Analyzed, n=number of participants with data for that time point.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 79
Measure Type: Number
Unit of Measure: percentage of participants
Overall onTRT visits: anti-ABA, n=39,77 2.6 1.3
Overall onTRT visits anti-CTLA4, n=40,78 5.0 3.8
Overall onTRT visits: Total, n=40,78 7.5 5.1
Overall post visits: anti-ABA, n=1,4 0 0
Overall post visits: anti-CTLA4, n=1,4 0 25
Overall post visits: Total, n=1,4 0 25
11.Secondary Outcome
Title RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL Over Time by DBW Treatment Group
Hide Description ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNC) Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing or negative.
Time Frame For on-treatment visits: Days 170-253, includes ≤21 Days after last dose or up to 1st dose of LTE Period. For follow-up post visits for participants who discontinued drug in RI: Day 22 after last dose of drug to Day 85 after last dose of drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in RI period with at least 1 immunogenicity result (ECL) during RI period N=Number of Participants Analyzed, n=number of participants with data for that time point
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 79
Measure Type: Number
Unit of Measure: percentage of participants
Overall onTRT visits CTLA4 and Possibly Ig,n=40,78 0 0
Overall onTRT visits Ig and/or JNC region, n=40,78 0 0
Overall onTRT visits: Total, n=40,78 0 0
Overall post visits: CTLA4 and possibly Ig, n=1,4 100.0 25.0
Overall post visits: Ig and/or JNC region, n=1,4 0 0
Overall post visits: Total, n=1,4 100.0 25.0
12.Secondary Outcome
Title Short Term (ST); Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 ELISA Antibody Responses by DBW Treatment Groups
Hide Description Serum samples from Abatacept-treated adult participants with active rheumatoid arthritis (RA) were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody. ST was defined as the LI Period, the DBW Period, and the RI Period (Days 1-253).
Time Frame For on-TRT visits: Days 1-253 (ST). For follow-up post visits for participants who discontinued drug in the ST: Day 22 after last dose of ST drug to Day 85 after last dose of ST drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in DBW period with at least 1 immunogenicity result (ELISA) during the Short Term. N=Number of Participants Analyzed, n=number of participants with data for that time point.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: percentage of participants
Overall study onTRT visits: anti-ABA, n=39,78 7.7 1.3
Overall study onTRT visits anti-CTLA4, n=40,80 5.0 8.8
Overall study onTRT visits: Total, n=40,80 12.5 10.0
Overall study post visits: anti-ABA, n=1, 4 0 0
Overall study post visits: anti-CTLA4, n=1, 4 0 25
Overall study post visits: Total, n=1, 4 0 25
Overall study anti-ABA, n=39, 78 7.7 1.3
Overall study anti-CTLA4, n=40, 80 5.0 8.8
Overall study Total, n=40,80 12.5 10.0
13.Secondary Outcome
Title Short Term: Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 ECL Antibody Responses by DBW Treatment Groups
Hide Description ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNC) Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing or negative.
Time Frame For on-TRT visits: Days 1-253 (ST). For follow-up post visits for participants who discontinued drug in the ST: Day 22 after last dose of ST drug to Day 85 after last dose of ST drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in DBW period with at least 1 immunogenicity result (ECL) during the Short Term. N=Number of Participants Analyzed, n=number of participants with data for that time point.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: percentage of Participants
Overall onTRT visits CTLA and possibly Ig,n=40,80 0 7.5
Overall onTRT visits Ig and/or JNC region,n=40,80 0 3.8
Overall study onTRT visits: Total, n=40,80 0 10
Overall post visits CTLA4 and possibly Ig,n=1,4 100.0 25.0
Overall post visits: Ig and/or JNC region, n=1,4 0 0
Overall study post visits: Total, n=1, 4 100.0 25.0
Overall study CTLA4 and possibly Ig,n=40,80 2.5 8.8
Overall study Ig and/or JNC region, n=40, 80 0 3.8
Overall study Total, n=40,80 2.5 11.3
14.Secondary Outcome
Title Short Term: Mean Change in Disease Activity Score (DAS) 28 (Using C-Reactive Protein [CRP]) From Baseline Over Time by DBW Treatment Groups
Hide Description The DAS28 is a continuous disease measure composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, the level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. DAS28 has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Clinically meaningful improvement= decrease in DAS28 score of ≥1.2 from baseline.
Time Frame Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
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Hide Analysis Population Description
Intent To Treat Analysis Population (DBW Period, Participants randomized in DBW period who received at least 1 dose of study medication in DBW period). N=Number of Participants Analyzed, n=number of participants with data for that time point and at baseline.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Mean (Standard Error)
Unit of Measure: units on a scale
Day 15, n=38, n=75 -0.64  (0.10) -0.87  (0.08)
Day 29, n=40, n=80 -1.07  (0.14) -1.10  (0.09)
Day 57, n=40. n=79 -1.39  (0.14) -1.62  (0.11)
Day 78, n=33, n=76 -1.76  (0.12) -1.89  (0.10)
Day 85, n=40, n=78 -1.97  (0.11) -1.88  (0.11)
Day 113, n=39, n=80 -1.78  (0.18) -1.69  (0.12)
Day 141, n=38, n=76 -1.81  (0.17) -1.54  (0.14)
Day 169, n=38, n=75 -2.03  (0.18) -1.49  (0.14)
Day 197, n=40, n=79 -2.14  (0.16) -1.92  (0.13)
Day 225, n=39, n=77 -2.20  (0.17) -2.04  (0.13)
Day 253, n=39, n=74 -2.22  (0.14) -2.32  (0.12)
15.Secondary Outcome
Title Short Term: Percentage of Participants Achieving Clinically Meaningful Improvement (CMI) in DAS 28 (CRP), Low Disease Activity (LDAS), or Clinical Remission Over Time by DBW Treatment Groups
Hide Description DAS28 is a continuous disease measure composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, the level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. DAS28 has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Clinically meaningful improvement= decrease in DAS28 score of ≥1.2 from baseline.
Time Frame Days 85, 169, and 253 (short term)
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Hide Analysis Population Description
Intent To Treat Analysis Population (DBW Period, Participants randomized in DBW period who received at least 1 dose of study medication in DBW period). N=Number of Participants Analyzed, n=number of participants with data for that time point and, when relevant, at baseline.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: percentage of participants
Day 85 CMI , n=40, n=78 80 76.9
Day 85 LDAS, n=40, n=78 67.5 62.8
Day 85 Clinical Remission, n=40, n=78 35.0 37.2
Day 169 CMI , n=38, n=75 78.9 57.3
Day 169 LDAS, n=38, n=75 68.4 54.7
Day 169 Clinical Remission, n=38, n=75 47.4 28.0
Day 253 CMI , n=39, n=74 87.2 89.2
Day 253 LDAS, n=39, n=74 69.2 79.7
Day 253 Clinical Remission, n=39, n=74 51.3 63.5
16.Secondary Outcome
Title Short Term; Mean Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline Over Time by DBW Treatment Groups
Hide Description The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
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Hide Analysis Population Description
Intent To Treat Analysis Population (DBW Period, Participants randomized in DBW period who received at least 1 dose of study medication in DBW period). N=Number of Participants Analyzed, n=number of participants with data for that time point and at baseline.
Arm/Group Title ABA [DBW] Placebo (PLA) [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Mean (Standard Error)
Unit of Measure: units on a scale
Day 15, n=40, n=77 -0.31  (0.06) -0.30  (0.04)
Day 29, n=40, n=80 -0.46  (0.05) -0.35  (0.04)
Day 57, n=40, n=79 -0.58  (0.09) -0.51  (0.06)
Day 78, n=33, n=77 -0.68  (0.10) -0.59  (0.07)
Day 85, n=40, n=79 -0.74  (0.09) -0.63  (0.07)
Day 113, n=40, n=80 -0.69  (0.08) -0.61  (0.06)
Day 141, n=39, n=78 -0.68  (0.10) -0.52  (0.07)
Day 169, n=38, n=76 -0.72  (0.11) -0.50  (0.07)
Day 197, n=40, n=79 -0.76  (0.09) -0.66  (0.06)
Day 225, n=40, n=77 -0.82  (0.10) -0.70  (0.06)
Day 253, n=39, n=74 -0.86  (0.09) -0.72  (0.06)
17.Secondary Outcome
Title Short Term; Percentage of Participants With HAQ-DI Response Over Time by DBW Treatment Groups
Hide Description The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
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Hide Analysis Population Description
Intent To Treat Analysis Population (DBW Period, Participants randomized in DBW period who received at least 1 dose of study medication in DBW period). N=Number of Participants Analyzed, n=number of participants with data for that time point and at baseline.
Arm/Group Title ABA [DB] PLA [DB]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: percentage of Participants
Day 15, n=40, n=77 47.5 42.9
Day 29, n=40, n=80 62.5 52.5
Day 57, n=40, n=79 67.5 62.0
Day 78, n=33, n=77 66.7 67.5
Day 85, n=40, n=79 80.0 69.6
Day 113, n=40, n=80 75.0 67.5
Day 141, n=39, n=78 69.2 62.8
Day 169, n=38, n=76 71.1 56.6
Day 197, n=40, n=79 75.0 74.7
Day 225, n=40, n=77 80.0 76.6
Day 253, n=39, n=74 84.6 74.3
18.Secondary Outcome
Title LI; Mean Change in DAS 28 (CRP) From Baseline Over Time
Hide Description DAS28 is a continuous disease measure composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, the level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. DAS28 has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Clinically meaningful improvement= decrease in DAS28 score of ≥1.2 from baseline.
Time Frame Days 1 (Baseline), 15, 29, 57, 78, 85
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication during LI period. N=Number of Participants Analyzed, n=number of participants with data for that time point and at baseline.
Arm/Group Title ABA [LI]
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Mean (Standard Error)
Unit of Measure: units on a scale
Day 15, n=150 -0.72  (0.06)
Day 29, n=165 -1.00  (0.07)
Day 57, n=164 -1.35  (0.08)
Day 78, n=143 -1.39  (0.10)
Day 85, n=161 -1.53  (0.10)
19.Secondary Outcome
Title LI; Percentage of Participants With Clinically Meaningful Improvement in DAS (CRP) Over Time
Hide Description DAS28 is a continuous disease measure composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, the level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. DAS28 has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Clinically meaningful improvement= decrease in DAS28 score of ≥1.2 from baseline.
Time Frame Days 15, 29, 57, 78, 85
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication during LI period. N=Number of Participants Analyzed, n=number of participants with data for that time point and at baseline.
Arm/Group Title ABA [LI]
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Measure Type: Number
Unit of Measure: percentage of participants
Day 15, n=150 26.0
Day 29, n=165 40.6
Day 57, n=164 56.1
Day 78, n=143 59.4
Day 85, n=161 64.6
20.Secondary Outcome
Title DBW Period; Mean Change in DAS 28 (CRP) From DBW Period Baseline (Day 85) Over Time
Hide Description DAS28 is a continuous disease measure composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, the level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. DAS28 has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Clinically meaningful improvement= decrease in DAS28 score of ≥1.2 from baseline.
Time Frame Days 85 (Period 2 Baseline), 113, 141, and 169
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Hide Analysis Population Description
Intent To Treat Analysis Population (DBW Period, Participants randomized in DBW period who received at least 1 dose of study medication in DBW period). N=Number of Participants Analyzed, n=number of participants with data for that time point and at DBW period baseline.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Mean (Standard Error)
Unit of Measure: units on a scale
Day 113, n=39, n=76 0.19  (0.18) 0.16  (0.11)
Day 141 , n=38, n=73 0.14  (0.17) 0.35  (0.15)
Day 169, n=38, n=72 -0.06  (0.19) 0.40  (0.14)
21.Secondary Outcome
Title DBW Period; Percentage of Participants With Rheumatoid Arthritis (RA) Flare Over Time
Hide Description

A participant had an RA flare if at least 2 of the following criteria were met:

  • Doubling of tender and swollen joint count from Day 78
  • Increase in DAS28-CRP score ≥ 1.2 from Day 78
  • Prematurely discontinued from Double-blind Withdrawal Period (Period 2) and continued to Re-introduction Period (Period 3)
Time Frame Days 85, 113, 141, and 169
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Hide Analysis Population Description
Intent To Treat Analysis Population (DBW Period, Participants randomized in DBW period who received at least 1 dose of study medication in DBW period). N=Number of Participants Analyzed, n=number of participants with data for that time point.
Arm/Group Title ABA [DB] PLA [DB]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: percentage of participants
Day 85, n=31, n=66 0 1.5
Day 113, n=33, n=77 9.1 2.6
Day 141, n=32, n=73 6.3 6.8
Day 169, n=33, n=74 6.1 9.5
22.Secondary Outcome
Title RI Period; Mean Change in DAS 28 (CRP) From RI Period Baseline (Day 169) Over Time
Hide Description DAS28 is a continuous disease measure composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, the level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. DAS28 has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Clinically meaningful improvement= decrease in DAS28 score of ≥1.2 from baseline.
Time Frame Days 169 (Period III Baseline), 197, 225, and 253
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Hide Analysis Population Description
Participants who received at least 1 dose of study medication during RI period. N=Number of Participants Analyzed, n=number of participants with data for that time point and at RI period baseline.
Arm/Group Title ABA With IV PLA Loading Dose [RI] PLA Switched to ABA With ABA IV Loading Dose [RI] PLA Switched to ABA With PLA IV Loading Dose [RI]
Hide Arm/Group Description:
Participants received a single placebo IV dose on Day 169, and continued weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg).
Participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Overall Number of Participants Analyzed 40 35 44
Mean (Standard Error)
Unit of Measure: units on a scale
Day 197, n=39, n=33, n=44 -0.26  (0.17) -0.56  (0.17) -0.50  (0.16)
Day 225, n=38, n=33, n=42 -0.31  (0.20) -0.59  (0.18) -0.66  (0.17)
Day 253, n=38, n=30, n=42 -0.23  (0.16) -0.93  (0.20) -0.89  (0.17)
23.Secondary Outcome
Title LI; Number of Participants With Deaths, Serious Adverse Events (SAEs), SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication during LI period
Arm/Group Title ABA [LI]
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Measure Type: Number
Unit of Measure: participants
Deaths 1
SAEs 3
Related SAEs 0
SAEs Leading to Discontinuation 1
AEs 82
Related AEs 29
AEs Leading to Discontinuation 1
24.Secondary Outcome
Title LI Period; Number of Participants With AEs of Special Interest
Hide Description AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections and opportunistic infections; autoimmune disorders; malignancies; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion), peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion),local injection site reaction (pre-specified AEs occurring at the site of SC injection)and systemic injection site reactions (pre-specified systemic AEs such as hypersensitivity reactions occurring within 24 hours of SC injection)
Time Frame From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication during LI period
Arm/Group Title ABA [LI]
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Measure Type: Number
Unit of Measure: participants
Infections and infestations 42
Malignancies 0
Autoimmune events (prespecified) 0
Acute infusional events (prespecified) 1
Peri-infusional events (prespecified) 2
Local injection site reactions (prespecified) 2
Systemic injection reactions (prespecified) 9
25.Secondary Outcome
Title LI; Number of Participants With Hematology Values Meeting the Marked Abnormality (MA) Criteria
Hide Description Upper Normal Limit (ULN), Lower Normal Limit (LLN), Baseline (BL). Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <LLN; neutrophils+bands: <1.0 * 10^3 cells/ microliter (uL); eosinophils: >0.750 * 10^3 cells/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 cells/uL/ >7.50 * 10^3 cells/uL.
Time Frame From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication during LI period.
Arm/Group Title ABA [LI]
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Measure Type: Number
Unit of Measure: participants
Low HGB 0
Low hematocrit 0
Low erythrocytes 1
Low PLT 1
High PLT 0
Low leukocytes 3
High leukocytes 4
Low neutrophils+bands 0
High eosinophils 1
High basophils 0
High monocytes 0
Low lymphocytes 7
High lymphocytes 0
26.Secondary Outcome
Title LI; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria
Hide Description Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL
Time Frame From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication during LI period.
Arm/Group Title ABA [LI]
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Measure Type: Number
Unit of Measure: participants
High ALP 0
High AST 1
High ALT 2
High GGT 0
High bilirubin 0
High BUN 1
High creatinine 3
27.Secondary Outcome
Title LI; Number of Participants With Electrolyte Values Meeting the Marked Abnormality Criteria
Hide Description Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL<LLN then use <0.95* BL or >ULN, or if BL>ULN then use>1.05* BL or <LLN; potassium (K): <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; (Cl): <0.9* LLN/>1.1* ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; calcium (Ca): <0.8* LLN/>1.2* ULN, or if BL<LLN then use <0.75* BL or >ULN, or if BL>ULN then use>1.25* BL or <LLN; phosphorous (P): <0.75* LLN/ >1.25* ULN, or if BL<LLN then use 0.67* BL or >ULN, or if BL>ULN then use>1.33* BL or <LLN
Time Frame From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication during LI period.
Arm/Group Title ABA [LI]
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Measure Type: Number
Unit of Measure: participants
Low Na 0
High Na 0
Low K 0
High K 0
Low Cl 0
High Cl 0
Low Ca 0
High Ca 0
Low P 1
High P 1
28.Secondary Outcome
Title LI; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria
Hide Description MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*upper limits of normal (ULN),or if BL< lower limits of normal (LLN) then use 0.8*BL or > upper limits of normal (ULN),or if BL>ULN then use >2.0*BL or <LLN;total protein: <0.9*LLN/>1.1*ULN,or if BL<LLN then use <0.9*BL or >ULN,or if BL>UNL then use >1.1*BL or <LLN; albumin: <0.9*LLN,or if BL<LLN then use <0.75 BL;uric acid: >1.5*ULN,or if BL>ULN then use >2*BL. Urinalysis: Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells (RBCs), White Blood Cells (WBCs):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3
Time Frame From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication during LI period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available during LI period.
Arm/Group Title ABA [LI]
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Measure Type: Number
Unit of Measure: participants
Low Glu (n=167) 9
High Glu (n=167) 4
Low fasting Glu (n=92) 3
High fasting glucose (n=92) 0
Low protein (n=167) 1
High protein (n=167) 1
Low Albumin (n=167) 0
High uric acid (n=167) 0
High urine protein (n=167) 3
High urine Glu (n=167) 3
High urine blood (n=167) 17
High leukocyte esterase (n=46) 9
High urine RBC (n=44) 7
High urine WBC (n=63) 26
29.Secondary Outcome
Title LI Period; Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Hide Description Blood pressure was taken in participants while seated and measured in millimeters of mercury (mmHg). Pressures were assessed at screening, at baseline on Day 1 prior to infusion of IV abatacept, at 30 and 60 minutes after IV infusion of abatacept on Day 1, and at all office visits prior to SC injection of abatacept. Vital signs were also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Time Frame Days 1, 15, 29, 57, 78, and 85
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication during LI period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point during the LI period.
Arm/Group Title ABA [LI]
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Mean (Standard Deviation)
Unit of Measure: mmHg
Day 1 SBP before infusion (n=160) 125.0  (18.42)
Day 15 SBP before injection (n=156) 122.3  (14.55)
Day 29 SBP before injection (n=161) 122.0  (14.02)
Day 57 SBP before injection (n=157) 121.4  (14.87)
Day 78 SBP before injection (n=157) 120.3  (14.38)
Day 85 SBP before injection (n=159) 122.0  (15.19)
Day 1 DBP before infusion (n=160) 76.0  (10.88)
Day 15 DBP before injection (n=156) 75.8  (9.63)
Day 29 DBP before injection (n=161) 76.1  (9.43)
Day 57 DBP before injection (n=157) 75.7  (9.82)
Day 78 DBP before injection (n=157) 75.4  (10.29)
Day 85 DBP before injection (n=159) 75.2  (9.45)
30.Secondary Outcome
Title LI Period; Mean Heart Rate (HR)
Hide Description Heart rate was taken in participants while seated and measured in beats per minute (bpm). Heart rate was assessed at screening, at baseline on Day 1 prior to infusion of IV abatacept, at 30 and 60 minutes after IV infusion of abatacept on Day 1, and at all office visits prior to SC injection of abatacept. Heart rate was also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Time Frame Days 1, 15, 29, 57, 78, and 85
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication during LI period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point during the LI period.
Arm/Group Title ABA [LI]
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Mean (Standard Deviation)
Unit of Measure: bpm
Day 1 HR before infusion (n=167) 73.9  (9.78)
Day 15 HR before injection (n=160) 76.0  (7.91)
Day 29 HR before injection (n=166) 75.5  (9.03)
Day 57 HR before injection (n=164) 75.5  (8.95)
Day 78 HR before injection (n=158) 75.1  (7.78)
Day 85 HR before injection (n=160) 74.7  (8.64)
31.Secondary Outcome
Title LI Period; Mean Temperature (T)
Hide Description Temperature was taken in participants while seated and measured in degrees celsius. Temperature was assessed at screening, at baseline on Day 1 prior to infusion of IV abatacept, at 30 and 60 minutes after IV infusion of abatacept on Day 1, and at all office visits prior to SC injection of abatacept. Temperature was also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Time Frame Days 1, 15, 29, 57, 78, and 85
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication during LI period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point during the LI period.
Arm/Group Title ABA [LI]
Hide Arm/Group Description:
On Day 1, participants received a single intravenous (IV) ABA dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g). Following, participants received weekly subcutaneous (SC) of open-label ABA (fixed dose of 125 mg) through Day 78.
Overall Number of Participants Analyzed 167
Mean (Standard Deviation)
Unit of Measure: degrees Celsius
Day 1 T before infusion (n=167) 36.39  (0.387)
Day 15 T before injection (n=160) 36.34  (0.351)
Day 29 T before injection (n=166) 36.39  (0.371)
Day 57 T before injection (n=164) 36.38  (0.329)
Day 78 T before injection (n=158) 36.33  (0.333)
Day 85 T before injection (n=160) 36.35  (0.368)
32.Secondary Outcome
Title DBW; Number of Participants With Death, Serious SAEs, Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in DBW period
Arm/Group Title ABA [DBW] Placebo (PLA) [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: participants
Deaths 0 2
SAEs 0 2
Related SAEs 0 0
AEs Leading to Discontinuation 0 0
AEs 13 29
Related AEs 2 9
AEs Leading to Discontinuation 0 0
33.Secondary Outcome
Title DBW; Number of Participants With AEs of Special Interest
Hide Description AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections and opportunistic infections; autoimmune disorders; malignancies; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion), peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion),local injection site reaction (pre-specified AEs occurring at the site of SC injection)and systemic injection site reactions (pre-specified systemic AEs such as hypersensitivity reactions occurring within 24 hours of SC injection)
Time Frame From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in DBW period
Arm/Group Title ABA [DBW] Placebo (PLA) [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: participants
Infections and infestations 5 7
Malignancies 0 0
Autoimmune disorders (prespecified) 0 0
Acute infusional events (prespecified) 0 0
Peri-infusional events (prespecified) 0 0
Local injection site reactions (prespecified) 0 0
Systemic injection reactions (prespecified) 1 1
34.Secondary Outcome
Title DBW; Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria
Hide Description Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <LLN; neutrophils+bands: <1.0 * 10^3 cells/uL; eosinophils: >0.750 * 10^3 cells/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 cells/uL/ >7.50 * 10^3 cells/uL.
Time Frame From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in DBW period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available during the DBW period.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: participants
Low HGB (n=40, n=80) 0 0
Low hematocrit (n=39, n=79) 0 0
Low erythrocytes (n=40, n=80) 0 0
Low PLT (n=40, n=80) 0 0
High PLT (n=40, n=80) 0 0
Low leukocytes (n=40, n=80) 0 1
High leukocytes (n=40, n=80) 0 0
Low neutrophils+bands (n=40, n=80) 0 0
High eosinophils (n=40, n=80) 0 2
High basophils (n=40, n=80) 0 0
High monocytes (n=40, n=80) 0 0
Low lymphocytes (n=40, n=80) 2 4
High lymphocytes (n=40, n=80) 0 0
35.Secondary Outcome
Title DBW; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria
Hide Description Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL
Time Frame From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in DBW period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available during the DBW period.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: participants
High ALP 0 0
High AST 0 0
High ALT 1 0
High GGT 2 0
High bilirubin 0 0
High BUN 0 0
High creatinine 0 1
36.Secondary Outcome
Title DBW; Number of Participants With Electrolytes Values Meeting the Marked Abnormality Criteria
Hide Description Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL<LLN then use <0.95* BL or >ULN, or if BL>ULN then use>1.05* BL or <LLN; potassium (K): <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; (Cl): <0.9* LLN/>1.1* ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; calcium (Ca): <0.8* LLN/>1.2* ULN, or if BL<LLN then use <0.75* BL or >ULN, or if BL>ULN then use>1.25* BL or <LLN; phosphorous (P): <0.75* LLN/ >1.25* ULN, or if BL<LLN then use 0.67* BL or >ULN, or if BL>ULN then use>1.33* BL or <LLN
Time Frame From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in DBW period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available during the DBW period.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: participants
Low Na 0 0
High Na 0 0
Low K 0 0
High K 0 0
Low Cl 0 0
High Cl 0 0
Low Ca 0 0
High Ca 0 0
Low P 0 0
High P 0 0
37.Secondary Outcome
Title DBW; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria
Hide Description MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*ULN,or if BL<LLN then use 0.8*BL or >ULN,or if BL>ULN then use >2.0*BL or <LLN;total protein: <0.9*LLN/>1.1*ULN,or if BL<LLN then use <0.9*BL or >UNL,or if BL>UNL then use >1.1*BL or <LLN; albumin: <0.9*LLN,or if BL<LLN then use <0.75 BL;uric acid: >1.5*ULN,or if BL>ULN then use >2*BL. Urinalysis (Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells [RBCs], White Blood Cells [WBCs]):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3
Time Frame From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in DBW period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available during the DBW period.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Measure Type: Number
Unit of Measure: participants
Low Glu (n=40, n=80) 2 5
High Glu (n=40, n=80) 1 3
Low fasting Glu (n=27, n=51) 0 1
High fasting Glu (n=27, n=51) 0 1
Low total protein (n=40, n=80) 0 0
High total protein (n=40, n=80) 0 0
Low albumin (n=40, n=80) 0 0
High uric acid (n=40, n=80) 0 0
High urine protein (n=40, n=80) 1 0
High urine Glu (n=40, n=80) 0 1
High urine blood (n=40, n=80) 3 10
High leukocyte esterase (n=10, n=21) 1 4
High urine RBC (n=13, n=23) 1 5
High urine WBC (n=15, n=28) 6 12
38.Secondary Outcome
Title DBW; Mean Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During Double Blind Period
Hide Description Blood pressures were taken in participants while seated, just prior to study drug injection, and measured in millimeters of mercury (mmHg).
Time Frame Days 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in DBW period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Mean (Standard Deviation)
Unit of Measure: mm mercury (Hg)
Day 113 SBP before injection (n=39, n=78) 119.4  (13.29) 120.4  (15.60)
Day 141 SBP before injection (n=39, n=76) 120.3  (12.73) 121.2  (14.98)
Day 169 SBP before injection (n=40, n=80) 119.6  (13.87) 119.4  (14.11)
Day 113 DBP before injection (n=39, 78) 74.2  (10.44) 74.4  (9.34)
Day 141 DBP before injection (n=39, n=76) 76.3  (10.46) 76.0  (10.60)
Day 169 DBP before injection (n=40, n=80) 74.0  (9.51) 74.7  (8.94)
39.Secondary Outcome
Title DBW Period; Mean Heart Rate (HR) During Period 2
Hide Description Heart Rate was taken in participants while seated, just prior to study drug injection, and measured in beats per minute (bpm)
Time Frame Days 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in DBW period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Mean (Standard Deviation)
Unit of Measure: beats per minute (bpm)
Day 113 HR before injection (n=40, n=78) 75.8  (8.07) 73.9  (8.39)
Day 141 HR before injection (n=39, n=76) 75.9  (9.35) 74.5  (8.45)
Day 169 HR before injection (n=40, n=80) 73.8  (8.19) 74.2  (8.50)
40.Secondary Outcome
Title DBW Period; Mean Temperature (T) During Period II
Hide Description Participants were seated and temperature taken just prior to study drug injection.
Time Frame Days 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in DBW period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point.
Arm/Group Title ABA [DBW] PLA [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 80
Mean (Standard Deviation)
Unit of Measure: degrees Celsius
Day 113 T before infusion (n=40, n=78) 36.34  (0.488) 36.44  (0.370)
Day 141 T before injection (n=39, n=76) 36.31  (0.355) 36.36  (0.347)
Day 169 T before injection (n=40, n=80) 36.38  (0.364) 36.32  (0.373)
41.Secondary Outcome
Title RI; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in RI period.
Arm/Group Title ABA With IV PLA Loading Dose [RI] PLA Switched to ABA With ABA IV Loading Dose [RI] PLA Switched to ABA With PLA IV Loading Dose [RI]
Hide Arm/Group Description:
Participants received a single placebo IV dose on Day 169, and continued weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg).
Participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Overall Number of Participants Analyzed 40 35 44
Measure Type: Number
Unit of Measure: participants
Deaths 0 0 0
SAEs 0 0 1
Related SAEs 0 0 0
SAEs Leading to Discontinuation 0 0 0
AEs 15 17 16
Related AEs 1 4 4
AEs Leading to Discontinuation 0 0 0
42.Secondary Outcome
Title RI; Number of Participants With AEs of Special Interest
Hide Description AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections and opportunistic infections; autoimmune disorders; malignancies; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion), peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion),local injection site reaction (pre-specified AEs occurring at the site of SC injection)and systemic injection site reactions (pre-specified systemic AEs such as hypersensitivity reactions occurring within 24 hours of SC injection)
Time Frame From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in RI period.
Arm/Group Title ABA With IV PLA Loading Dose [RI] PLA Switched to ABA With ABA IV Loading Dose [RI] PLA Switched to ABA With PLA IV Loading Dose [RI]
Hide Arm/Group Description:
Participants received a single placebo IV dose on Day 169, and continued weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg).
Participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Overall Number of Participants Analyzed 40 35 44
Measure Type: Number
Unit of Measure: participants
Infections and infestations 7 8 7
Malignancies 0 0 0
Autoimmune disorders (prespecified) 0 0 0
Acute infusional events (prespecified) 0 0 0
Peri-infusional events (prespecified) 0 0 1
Local injection site reactions (prespecified) 0 0 0
Systemic injection reactions (prespecified) 0 0 1
43.Secondary Outcome
Title RI; Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria
Hide Description Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <LLN; neutrophils+bands: <1.0 * 10^3 cells/uL; eosinophils: >0.750 * 10^3 cells/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 cells/uL/ >7.50 * 10^3 cells/uL.
Time Frame From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in RI period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available during the RI period.
Arm/Group Title ABA With IV PLA Loading Dose [RI] PLA Switched to ABA With ABA IV Loading Dose [RI] PLA Switched to ABA With PLA IV Loading Dose [RI]
Hide Arm/Group Description:
Participants received a single placebo IV dose on Day 169, and continued weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg).
Participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Overall Number of Participants Analyzed 40 35 44
Measure Type: Number
Unit of Measure: participants
Low HGB 0 0 0
Low hematocrit 0 0 0
Low erythrocytes 0 0 0
Low PLT 0 0 0
High PLT 0 0 0
Low leukocytes 0 0 0
High leukocytes 0 1 0
Low neutrophils+bands 0 0 0
High eosinophils 0 0 0
High basophils 0 0 0
High monocytes 0 0 0
Low lymphocytes 2 0 0
High lymphocytes 0 0 0
44.Secondary Outcome
Title RI; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria
Hide Description Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL
Time Frame From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in RI period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available during the RI period.
Arm/Group Title ABA With IV PLA Loading Dose [RI] PLA Switched to ABA With ABA IV Loading Dose [RI] PLA Switched to ABA With PLA IV Loading Dose [RI]
Hide Arm/Group Description:
Participants received a single placebo IV dose on Day 169, and continued weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg).
Participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Overall Number of Participants Analyzed 40 35 44
Measure Type: Number
Unit of Measure: participants
High ALP 0 0 0
High AST 0 0 0
High ALT 2 0 0
High GGT 1 0 0
High bilirubin 0 0 0
High BUN 0 0 0
High creatinine 0 0 0
45.Secondary Outcome
Title RI; Number of Participants With Electrolytes Values Meeting the Marked Abnormality Criteria
Hide Description Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL<LLN then use <0.95* BL or >ULN, or if BL>ULN then use>1.05* BL or <LLN; potassium (K): <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; (Cl): <0.9* LLN/>1.1* ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; calcium (Ca): <0.8* LLN/>1.2* ULN, or if BL<LLN then use <0.75* BL or >ULN, or if BL>ULN then use>1.25* BL or <LLN; phosphorous (P): <0.75* LLN/ >1.25* ULN, or if BL<LLN then use 0.67* BL or >ULN, or if BL>ULN then use>1.33* BL or <LLN
Time Frame From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in RI period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available during the RI period.
Arm/Group Title ABA With IV PLA Loading Dose [RI] PLA Switched to ABA With ABA IV Loading Dose [RI] PLA Switched to ABA With PLA IV Loading Dose [RI]
Hide Arm/Group Description:
Participants received a single placebo IV dose on Day 169, and continued weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg).
Participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Overall Number of Participants Analyzed 40 35 44
Measure Type: Number
Unit of Measure: participants
Low Na 0 0 0
High Na 0 0 0
Low K 0 0 1
High K 0 0 0
Low Cl 0 0 0
High Cl 0 0 0
Low Ca 0 0 0
High Ca 0 0 0
Low P 0 1 0
High P 0 0 0
46.Secondary Outcome
Title RI; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria
Hide Description MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*ULN,or if BL<LLN then use 0.8*BL or >ULN,or if BL>ULN then use >2.0*BL or <LLN;total protein: <0.9*LLN/>1.1*ULN,or if BL<LLN then use <0.9*BL or >UNL,or if BL>UNL then use >1.1*BL or <LLN; albumin: <0.9*LLN,or if BL<LLN then use <0.75 BL;uric acid: >1.5*ULN,or if BL>ULN then use >2*BL. Urinalysis (Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells [RBCs], White Blood Cells [WBCs]):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3
Time Frame From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in RI period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available during the RI period.
Arm/Group Title ABA With IV PLA Loading Dose [RI] PLA Switched to ABA With ABA IV Loading Dose [RI] PLA Switched to ABA With PLA IV Loading Dose [RI]
Hide Arm/Group Description:
Participants received a single placebo IV dose on Day 169, and continued weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg).
Participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Overall Number of Participants Analyzed 40 35 44
Measure Type: Number
Unit of Measure: participants
Low Glu (n=40, n=35, n=44) 1 1 1
High Glu (n=40, n=35, n=44) 0 1 0
Low fasting Glu (n=27, n=20, n=28) 1 0 0
High fasting glucose (n=27, n=20, n=28) 0 0 0
Low total protein (n=40, n=35, n=44) 0 0 0
High total protein (n=40, n=35, n=44) 0 0 0
Low albumin (n=40, n=35, n=44) 0 0 0
High uric acid (n=40, n=35, n=44) 0 0 0
High urine protein (n=40, n=35, n=44) 0 0 1
High urine glucose (n=40, n=34, n=44) 0 0 0
High urine blood (n=40, n=35, n=44) 6 4 7
High leukocyte esterase (n=14, n=8, n=7) 4 2 1
High urine RBC (n=17, n=14, n=15) 6 3 6
High urine WBC (n=19, n=15, n=15) 6 5 4
47.Secondary Outcome
Title RI Period; Mean Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During Period III
Hide Description [Not Specified]
Time Frame Days 169, 197, 225, and 253
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in RI period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point.
Arm/Group Title ABA With IV PLA Loading Dose [RI] PLA Switched to ABA With ABA IV Loading Dose [RI] PLA Switched to ABA With PLA IV Loading Dose [RI]
Hide Arm/Group Description:
Participants received a single placebo IV dose on Day 169, and continued weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg).
Participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Overall Number of Participants Analyzed 40 35 44
Mean (Standard Deviation)
Unit of Measure: mm mercury (Hg)
Day 169 SBP before infusion (n=39, n=35, n=44) 121.3  (15.81) 116.6  (14.78) 118.9  (13.32)
Day 197 SBP before injection (n=40, n=35, n=43) 119.1  (14.07) 118.4  (15.62) 121.0  (14.45)
Day 225 SBP before injection (n=40, n=35, n=42) 117.8  (14.19) 118.8  (16.55) 121.0  (16.88)
Day 253 SBP before injection (n=40, 35, n=43) 118.3  (15.00) 116.1  (14.86) 120.3  (16.01)
Day 169 DBP before infusion (n=39, n=35, n=44) 74.7  (10.46) 73.5  (9.61) 74.9  (9.15)
Day 197 DBP before injection (n=40, n=35, n=43) 72.9  (9.24) 71.6  (7.66) 74.9  (9.51)
Day 225 DBP before injection (n=40, n=35, n=42) 73.6  (10.56) 73.7  (7.84) 75.5  (10.65)
Day 253 DBP before injection (n=40, n=35, n=44) 74.7  (11.24) 71.5  (9.92) 76.3  (11.02)
48.Secondary Outcome
Title RI Period; Mean Heart Rate (HR) During Period III
Hide Description [Not Specified]
Time Frame Days 169, 197, 225, and 253
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in RI period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point.
Arm/Group Title ABA With IV PLA Loading Dose [RI] PLA Switched to ABA With ABA IV Loading Dose [RI] PLA Switched to ABA With PLA IV Loading Dose [RI]
Hide Arm/Group Description:
Participants received a single placebo IV dose on Day 169, and continued weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg).
Participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Overall Number of Participants Analyzed 40 35 44
Mean (Standard Deviation)
Unit of Measure: beats per minute (bpm)
Day 169 HR before infusion (n=40, n=35, n=44) 73.4  (8.54) 73.8  (10.13) 74.1  (9.35)
Day 197 HR before injection (n=40, n=35, n=43) 73.1  (7.52) 75.1  (7.25) 70.9  (8.87)
Day 225 HR before injection (n=40, n=35, n=42) 73.2  (7.0) 73.9  (7.43) 73.2  (7.60)
Day 253 HR before injection (n=40, n=35, n=43) 73.6  (8.53) 74.4  (7.87) 74.3  (9.36)
49.Secondary Outcome
Title RI Period; Mean Temperature (T) During Period III
Hide Description [Not Specified]
Time Frame Days 169, 197, 225, and 253
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in RI period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point.
Arm/Group Title ABA With IV PLA Loading Dose [RI] PLA Switched to ABA With ABA IV Loading Dose [RI] PLA Switched to ABA With PLA IV Loading Dose [RI]
Hide Arm/Group Description:
Participants received a single placebo IV dose on Day 169, and continued weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg).
Participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Overall Number of Participants Analyzed 40 35 44
Mean (Standard Deviation)
Unit of Measure: degrees Celsius
Day 169 T before infusion (n=40, n=35, n=44) 36.32  (0.423) 36.29  (0.473) 36.26  (0.396)
Day 197 T before injection (n=40, n=35, n=43) 36.39  (0.405) 36.37  (0.424) 36.35  (0.354)
Day 225 T before injection (n=40, n=35, n=42) 36.27  (0.375) 36.38  (0.444) 36.36  (0.320)
Day 253 T before injection (n=40, n=34, n=42) 36.28  (0.473) 36.32  (0.587) 36.33  (0.383)
50.Secondary Outcome
Title Short Term; Abatacept Serum Concentration by Immunogenicity Status as Measured by ELISA by RI Treatment Groups
Hide Description Pharmacokinetics is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Cmin=minimum observed plasma concentration of single-dose abatacept. Cmin for each participant was listed by study visit and immunogenicity status (seropositive vs. seronegative) was determined by ELISA.
Time Frame Day 197 through Day 253
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated during the RI Period with at least 1 immunogenicity result (ELISA) during this period. N=Number of Participants Analyzed, n=number of participants with data for that time point
Arm/Group Title ABA With IV PLA Loading Dose [RI] PLA Switched to ABA With ABA IV Loading Dose [RI] PLA Switched to ABA With PLA IV Loading Dose [RI]
Hide Arm/Group Description:
Participants received a single placebo IV dose on Day 169, and continued weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg).
Participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Overall Number of Participants Analyzed 40 35 44
Mean (Standard Deviation)
Unit of Measure: ug/mL
Day 197 seropositive (n=2, n=1, n=1) 39.17  (10.510) 33.73 [1]   (NA) 18.05 [1]   (NA)
Day 197 seronegative (n=33, n=32, n=40) 34.45  (10.578) 35.67  (10.365) 22.76  (8.740)
Day 225 seropositive (n=0, n=1, n=1) NA [2]   (NA) 34.18 [1]   (NA) 21.69 [1]   (NA)
Day 225 seronegative (n=36, n=29, n=41) 27.86  (9.514) 31.70  (10.635) 29.24  (13.897)
Day 253 seropositive (n=1, n=0, n=2) 29.49 [3]   (NA) NA [2]   (NA) 26.23  (0.776)
Day 253 seronegative (n=34, n=30, n=39) 30.17  (9.856) 28.26  (10.211) 26.80  (10.547)
[1]
Standard deviation not applicable for 1 participant.
[2]
Data not measured/analyzed for 0 participants.
[3]
Standard deviation no applicable for 1 participant.
51.Secondary Outcome
Title Short Term; Abatacept Serum Concentration by Immunogenicity Status as Measured by ECL by RI Treatment Groups
Hide Description Pharmacokinetics is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Cmin=minimum observed plasma concentration of single-dose abatacept. Cmin for each participant was listed by study visit and immunogenicity status (seropositive vs. seronegative) was determined by ECL.
Time Frame Day 197 through Day 253
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated in RI period with at least 1 immunogenicity result (ECL) during RI period. N=Number of Participants Analyzed, n=number of participants with data for that time point
Arm/Group Title ABA With IV PLA Loading Dose [RI] PLA Switched to ABA With ABA IV Loading Dose [RI] PLA Switched to ABA With PLA IV Loading Dose [RI]
Hide Arm/Group Description:
Participants received a single placebo IV dose on Day 169, and continued weekly SC injections of open-label ABA for 12 weeks (fixed dose of 125 mg).
Participants were randomized to receive a single ABA IV loading dose based on participant weight (<60 kg=500 mg, 60-100 kg=750 mg, >100 kg=1 g) and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Participants were randomized to receive a single PLA IV loading dose and weekly open-label SC ABA injections (fixed dose of 125 mg) were re-introduced.
Overall Number of Participants Analyzed 40 35 44
Mean (Standard Deviation)
Unit of Measure: ug/mL
Day 197 seropositive (n=0, n=0, n=0) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Day 197 seronegative (n=35, n=33, n=41) 34.72  (10.479) 35.61  (10.207) 22.65  (8.662)
Day 225 seropositive (n=0, n=0, n=0) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Day 225 seronegative (n=36, n=30, n=42) 27.86  (9.514) 31.79  (10.460) 29.06  (13.776)
Day 253 seropositive (n=0, n=0, n=0) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Day 253 seronegative (n=36, n=30, n=42\) 29.75  (9.872) 28.26  (10.211) 26.28  (10.645)
[1]
Data not measured/analyzed for 0 participants.
52.Secondary Outcome
Title ST; Number of Participants Positive for Anti-nuclear Antibody (ANA), Anti-double Stranded DNA Antibody (dsDNA), or Rheumatoid Factor (RF) at Day 253 According to Baseline Status (Negative at Baseline or Positive at Baseline) by DBW Treatment Groups
Hide Description Venous blood was collected and tested for anti-nuclear antibodies, anti-dsDNA antibodies, and rheumatoid factor. ANA were detected by means of immunofluorescent antibodies. An anti-DNA radioimmunoassay was used for detection of anti-dsDNA antibodies (Diagnostic Products Corporation). RF was measured by an immunoturbidimetric assay (Roche Tina-Quant). Determinations of antibody or RF status were made at baseline and Day 253.
Time Frame Baseline, Day 253
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated in DBW period with at least 1 immunogenicity result (immunofluorescence, radioimmunoassay, or immunoturbidimetry) during this period. N=Number of Participants Analyzed, n=number of participants with data for that time point
Arm/Group Title ABA [DBW] Placebo (PLA) [DBW]
Hide Arm/Group Description:
Participants received ABA SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks.
Participants received PLA SC injections starting on Day 85 and weekly for 12 weeks.
Overall Number of Participants Analyzed 40 79
Measure Type: Number
Unit of Measure: participants
BL ANA negative (n=27, n=57) 1 3
BL ANA positive (n=11, 18) 5 10
BL dsDNA negative (n=33, n=63) 1 2
BL dsDNA positive (n=3, n=6) 2 3
BL RF negative (n=6, n=10) 0 0
BL RF positive (n=34, n=64) 34 63
53.Secondary Outcome
Title LTE: DAS28-CRP Mean Change From Baseline (Day 1) Over Time - All Participants Treated in LTE
Hide Description DAS28=continuous disease measure composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28, level of serum reactant protein CRP, and participant global assessment of disease activity measured on a visual analogue scale. DAS28-CRP has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Last day of ST is Day 85 for Period I Nonresponders and Day 253 for ST Completers . Data are not available(NA) for the period from Day 113 to Day 253 for Period 1 non-responders. Note: Day 85 and Day 337 assessments for the Period I Nonresponder cohort in fact represent consecutive assessments with an interval of approximately 1 month. For Period I nonresponder, study days do not represent treatment days. Study Day 337 for a Period I nonresponder actually corresponds to that participant's Treatment Day 169.
Time Frame For Period 1 non-responders: as of Study Day 85 and up to Day 1821. For ST completers: as of Study Day 253 and up to Day 1821.
Hide Outcome Measure Data
Hide Analysis Population Description
The LTE Treated Population contained those participants who received at least 1 dose of study medication during the LTE. Participants in LTE either completed Period 3 or were nonresponders at the end of Period 1. n=number of participants with both baseline and post-baseline measurements.
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 36 113
Mean (Standard Error)
Unit of Measure: units on a scale
Study Day 15; Treatment Day 15 (n=31, 106) -0.48  (0.14) -0.79  (0.06)
Study Day 85; Treatment Day 85 (n=36, 112) -0.35  (0.21) -1.91  (0.09)
Study Day 253; Treatment Day 85 (n=0, n=109) NA [1]   (NA) -2.29  (0.09)
Study Day 337; Treatment Day 169 (n=34,n=113) -1.51  (0.16) -2.34  (0.09)
Study Day 365; Treatment Day 197 (n=31, n=110) -1.83  (0.19) -2.23  (0.10)
Study Day 533; Treatment Day 365 (n=32, n=106) -1.86  (0.19) -2.28  (0.12)
Study Day 729; Treatment Day 561 (n=30, n=106 -1.81  (0.19) -2.16  (0.12)
Study Day 1093; Treatment Day 925 (n=26, n=98) -1.94  (0.18) -2.12  (0.12)
Study Day 1261; Treatment Day 1093 (n=25, n=96) -1.70  (0.15) -2.20  (0.13)
Study Day 1821; Treatment Day 1653 (n=20, n=67) -1.86  (0.20) -2.55  (0.14)
[1]
No data collected. 0 participants available. Period 1 non-responders started LTE on Study Day 85, not Study Day 253.
54.Secondary Outcome
Title LTE: Percent of Participants Who Achieved Clinical Remission in the Long Term Extension - All Participants Treated in LTE
Hide Description DAS28=continuous disease measure composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28, level of serum reactant protein CRP, and participant global assessment of disease activity measured on a visual analogue scale. Clinical remission=DAS28-CRP score<2.6. Percent=Number of participants meeting remission divided by number of participants evaluated. Last day of ST is Day 85 for Period I Nonresponders and Day 253 for ST Completers . Data are not available (NA) for the period from Day 113 to Day 253 for Period 1 non-responders. Note: Day 85 and Day 337 assessments for the Period I Nonresponder cohort in fact represent consecutive assessments with an interval of approximately 1 month. For Period I nonresponder, study days do not represent treatment days. Study Day 337 for a Period I nonresponder actually corresponds to that participant's Treatment Day 169.
Time Frame For Period I non-responders: as of Study Day 85 and up to Study Day 1821. For ST completers: as of Study Day 253 and up to Study Day 1821
Hide Outcome Measure Data
Hide Analysis Population Description
The LTE Treated Population contained those participants who received at least 1 dose of study medication during the LTE. Participants in LTE either completed Period 3 or were nonresponders at the end of Period 1. n= number of participants evaluated at each specific timepoint
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 36 113
Measure Type: Number
Unit of Measure: percentage of participants
Study Day 85 (n=36, n=112) 11.1 36.6
Study Day 253 (n=0, n=109) NA [1]  59.6
Study Day 337 (n=34, n=113) 50.0 59.3
Study Day 729 (n=30, n=106) 53.3 54.7
Study Day 1093 (n=26, 90) 73.1 51.0
Study Day 1261 (n=25, n=96) 48.0 59.4
Study Day 1821 (n=20, n=67) 60.0 59.7
[1]
no data available. 0 participants. Period 1 non-responders entered LTE on Study Day 85, not Study Day 253.
55.Secondary Outcome
Title LTE: Percent of Participants With Low Disease Activity in Long Term Extension: All Participants Treated in LTE
Hide Description DAS28:continuous disease measure composite of 4 variables: number of tender joints out of 28 joints, number of swollen joints out of 28 joints, level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. Low disease activity score: ≤ 3.2. Percent=Number of participants with Low Disease Activity divided by number of participants evaluated. Last day of ST is Day 85 for Period I Nonresponders and Day 253 for ST Completers . Data are not available(NA) for the period from Day 113 to Day 253 for Period 1 non-responders. Note: Day 85 and Day 337 assessments for the Period I Nonresponder cohort in fact represent consecutive assessments with an interval of approximately 1 month. For Period I nonresponder, study days do not represent treatment days. Study Day 337 for a Period I nonresponder actually corresponds to that participant's Treatment Day 169.
Time Frame For Period 1 non-responders: as of Study Day 85 and up to Day 1821. For ST completers: as of Study Day 253 and up to Day 1821.
Hide Outcome Measure Data
Hide Analysis Population Description
The LTE Treated Population contained those participants who received at least 1 dose of study medication during the LTE. Participants in LTE either completed Period 3 or were nonresponders at the end of Period 1.
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 36 113
Measure Type: Number
Unit of Measure: percentage of participants
Study Day 85 (n=36, n=112) 27.8 66.1
Study Day 253 (n=0, n=109) NA [1]  75.2
Study Day 337 (n=34, n=113) 67.6 76.1
Study Day 729 (n=30, n=106) 73.3 73.6
Study Day 1093 (n=26, n=98) 80.8 67.3
Study Day 1261 (n=25, n=96) 68.0 75.0
Study Day 1821 (n=20, n=67) 80.0 88.1
[1]
no data available. 0 participants. Period 1 non-responders entered LTE on Study Day 85, not Study Day 253.
56.Secondary Outcome
Title LTE: Percent of Participants With HAQ Response Over Time - All Participants Treated in LTE
Hide Description The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index (DI) was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ DI. Percent=number of participants with HAQ response divided by number of participants in the analysis. Since Period I Non-responders proceeded directly to the LTE at the end of Period I (Day 85), study days do not represent treatment days.
Time Frame Study Days 1 (Baseline),15, 29, 57, 78, 85, 253, 337, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541,1625,1709,1821,1905,1989, 2073
Hide Outcome Measure Data
Hide Analysis Population Description
The LTE Treated Population contained those participants who received at least 1 dose of study medication during the LTE. Participants in LTE either completed Period 3 or were non-responders at the end of Period 1. n= number of participants with data who were evaluated
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 37 113
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Study Day 15; Treatment Day 15 (n=34, n=110)
20.6
(7.0 to 34.2)
44.5
(35.3 to 53.8)
Study Day 29; Treatment Day 29 (n=36, n=113)
27.8
(13.1 to 42.4)
56.6
(47.5 to 65.8)
Study Day 57; Treatment Day 57 (n=36, n=112)
44.4
(28.2 to 60.7)
64.3
(55.4 to 73.2)
Study Day 78; Treatment Day 78 (n=34, n=103)
41.2
(24.6 to 57.7)
68.0
(58.9 to 77.0)
Study Day 85; Treatment Day 85 (n=37, n=112)
40.5
(24.7 to 56.4)
74.1
(66.0 to 82.2)
Study Day 253; Treatment Day 85 (n=0, n=109)
NA [1] 
(NA to NA)
78.0
(70.2 to 85.8)
Study Day 337; Treatment Day 169 (n=34, n=113)
50.0
(33.2 to 66.8)
79.6
(72.2 to 87.1)
Study Day 365; Treatment Day 197 (n=32, n=111)
53.1
(35.8 to 70.4)
78.4
(70.7 to 86.0)
Study Day 449; Treatment Day 281 (n=32, n=109)
56.3
(39.1 to 73.4)
73.4
(65.1 to 81.7)
Study Day 533; Treatment Day 365 (n=32, n=108)
59.4
(42.4 to 76.4)
72.2
(63.8 to 80.7)
Study Day 617; Treatment Day 449 (n=31, n=107)
54.8
(37.3 to 72.4)
70.1
(61.4 to 78.8)
Study Day 729; Treatment Day 561 (n=30, n=107)
60.0
(42.5 to 77.5)
70.1
(61.4 to 78.8)
Study Day 813; Treatment Day 645 (n=30, n=106)
53.3
(35.5 to 71.2)
71.7
(63.1 to 80.3)
Study Day 897; Treatment Day 729 (n=30, n=103)
50.0
(32.1 to 67.9)
76.7
(68.5 to 84.9)
Study Day 981; Treatment Day 813 (n=29, n=100)
44.8
(26.7 to 62.9)
73.0
(64.3 to 81.7)
Study Day 1093; Treatment Day 925 (n=28, n=99)
50.0
(31.5 to 68.5)
73.7
(65.1 to 82.4)
Study Day 1177; Treatment Day 1009 (n=26, n=99)
61.5
(42.8 to 80.2)
68.7
(59.6 to 77.8)
Study Day 1261; Treatment Day 1093 (n=25, n=97)
60.0
(40.8 to 79.2)
70.1
(61.0 to 79.2)
Study Day 1345; Treatment Day 1177 (n=25, n=89)
64.0
(45.2 to 82.8)
70.8
(61.3 to 80.2)
Study Day 1457; Treatment Day 1289 (n=24, n=79)
66.7
(47.8 to 85.5)
72.2
(62.3 to 82.0)
Study Day 1541; Treatment Day 1373 (n=21, n=75)
61.9
(41.1 to 82.7)
69.3
(58.9 to 79.8)
Study Day 1625; Treatment Day 1457 (n=21, n=73)
52.4
(31.0 to 73.7)
74.0
(63.9 to 84.0)
Study Day 1709; Treatment Day 1541 (n=20, n=71)
60.0
(38.5 to 81.5)
74.6
(64.5 to 84.8)
Study Day 1821; Treatment Day 1653 (n=20, n=68)
65.0
(44.1 to 85.9)
73.5
(63.0 to 84.0)
Study Day 1905; Treatment Day 1737 (n=19, n=5)
63.2
(41.5 to 84.8)
80.0
(44.9 to 100.0)
Study Day 1989; Treatment Day 1821 (n=19, n=0)
68.4
(47.5 to 89.3)
NA [2] 
(NA to NA)
Study Day 2073; Treatment Day 1905 (n=5, n=0)
100.0
(100.0 to 100.0)
NA [2] 
(NA to NA)
[1]
no data collected. 0 participants. Period 1 non-responders entered LTE on Study Day 85 not Study Day 253.
[2]
no data collected due to 0 participant available.
57.Secondary Outcome
Title LTE: Overall Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses (ECL Method) for On-Treatment Visits, Post Last Dose Visits, and Overall Study - All Participants Treated in LTE
Hide Description Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using electrochemiluminescence (ECL). The percent of participants with a positive abatacept induced immunogenicity response against cytotoxic T-lymphocyte antigen 4 (CTLA4) and possibly immunoglobulin (Ig), or against Ig and/or Junction Region was calculated by number of participants with a positive response divided by number of participants evaluated. Overall for on-treatment includes treatment visits on Days 337, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1457, 1625, 1821, and 1989.
Time Frame Days 337, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1457, 1625, 1821, 1989 and 28, 56, 85, 168 days post last dose in LTE
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in LTE period with at least 1 immunogenicity result (ECL) during LTE period. n=number of participants evaluated.
Arm/Group Title LTE Abatacept for All Participants
Hide Arm/Group Description:
This group includes all participants who received at least one dose of 125 mg SC Abatacept during the LTE and includes both the LI Period 1 non-responder and the ST Completer cohorts.
Overall Number of Participants Analyzed 149
Measure Type: Number
Unit of Measure: percentage of participants
Overall Study (n=149) 20.1
Overall on Treatment Visit Days (n=147) 15.6
28 Days post last dose (n=110) 7.3
56 Days post last dose (n=16) 6.3
85 Days post last dose (n=103) 7.8
168 Days post last dose (n=21) 23.8
Overall Post Visits (n=126) 12.7
58.Secondary Outcome
Title LTE: Number of Participants With Death, Related SAEs, SAEs Leading to Discontinuation, Related AEs, or AEs Leading to Discontinuation During Long Term Extension (LTE)
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. SAEs include hospitalizations for elective surgical procedures.All deaths reported during the LTE including those that occurred > 56 days after the last dose. Related AE or SAE defined as AE or SAE with Certain, Probable, Possible, or Missing relationship to study medication. All participants who completed the ST period could enter the open label LTE on Day 253; LI Period 1 non-responders could directly enter the LTE.
Time Frame For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014), up to 56 days post last dose. For ST completers: as of Day 253 and up to completion of LTE (FEB 2014) up to 56 days post last dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in LTE period
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, could enter the LTE on Day 253 and receive weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 37 113
Measure Type: Number
Unit of Measure: participants
Deaths 1 6
Related SAEs 0 3
SAEs Leading to Discontinuation 1 5
Related AEs 9 45
AEs Leading to Discontinuation 2 5
59.Secondary Outcome
Title LTE: Number of Participants With AEs of Special Interest During LTE
Hide Description AEs of special interest in LTE are those AEs that may be associated with the use of immunomodulatory drugs, including all infections and opportunistic infections; autoimmune disorders; malignancies, local injection site reaction (pre-specified AEs occurring at the site of SC injection) and systemic injection site reactions (pre-specified systemic AEs such as hypersensitivity reactions occurring within 24 hours of SC injection)
Time Frame For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014) up to 56 days post last dose. For ST completers: as of Day 253 and up to completion of LTE (FEB 2014) up to 56 days post last dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in LTE period
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 37 113
Measure Type: Number
Unit of Measure: participants
Infections and infestations 23 78
Malignancies 1 3
Autoimmune disorders (prespecified) 3 8
Local injection site reactions (prespecified) 0 3
Systemic injection reactions (prespecified) 3 11
60.Secondary Outcome
Title LTE: Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria During LTE
Hide Description Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <LLN; neutrophils+bands: <1.0 * 10^3 cells/uL; eosinophils: >0.750 * 10^3 cells/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 cells/uL/ >7.50 * 10^3 cells/uL.
Time Frame For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in LTE period and who had data available during the LTE period.
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 35 113
Measure Type: Number
Unit of Measure: participants
Low HGB 1 4
Low hematocrit 0 2
Low erythrocytes 0 1
Low PLT 0 1
Low leukocytes 1 5
High leukocytes 0 6
Low neutrophils+bands 0 2
High eosinophils 3 14
Low lymphocytes 5 9
61.Secondary Outcome
Title LTE: Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria During LTE
Hide Description Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL
Time Frame For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in LTE period and who had data available during the LTE period.
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 35 113
Measure Type: Number
Unit of Measure: participants
High AST 0 3
High ALT 2 2
High GGT 1 8
High bilirubin 0 1
High BUN 0 7
High creatinine 4 11
62.Secondary Outcome
Title LTE: Number of Participants With Electrolyte Values Meeting the Marked Abnormality Criteria During LTE
Hide Description Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL<LLN then use <0.95* BL or >ULN, or if BL>ULN then use>1.05* BL or <LLN; potassium (K): <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; (Cl): <0.9* LLN/>1.1* ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; calcium (Ca): <0.8* LLN/>1.2* ULN, or if BL<LLN then use <0.75* BL or >ULN, or if BL>ULN then use>1.25* BL or <LLN; phosphorous (P): <0.75* LLN/ >1.25* ULN, or if BL<LLN then use 0.67* BL or >ULN, or if BL>ULN then use>1.33* BL or <LLN
Time Frame For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in LTE period and who had data available during the LTE period.
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 35 113
Measure Type: Number
Unit of Measure: participants
High Na 1 0
Low K 0 3
High Cl 1 0
Low P 0 5
High P 1 0
63.Secondary Outcome
Title LTE: Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria During LTE
Hide Description MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*ULN,or if BL<LLN then use 0.8*BL or >ULN,or if BL>ULN then use >2.0*BL or <LLN;total protein: <0.9*LLN/>1.1*ULN,or if BL<LLN then use <0.9*BL or >UNL,or if BL>UNL then use >1.1*BL or <LLN; albumin: <0.9*LLN,or if BL<LLN then use <0.75 BL;uric acid: >1.5*ULN,or if BL>ULN then use >2*BL. Urinalysis (Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells [RBCs], White Blood Cells [WBCs]):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3
Time Frame For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in LTE period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available during the LTE period.
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 35 113
Measure Type: Number
Unit of Measure: participants
Low Glu (n=35, n=113) 6 16
High Glu (n=35, n=113) 1 6
Low fasting Glu (n=14, n=75) 4 2
High fasting Glu (n=14, n=75) 0 6
Low total protein (n=35, n=113) 1 0
Low albumin (n=35, n=113) 1 0
High urine protein (n=35, n=113) 2 11
High urine Glu (n=35, n=113) 1 3
High urine blood (n=35, n=113) 5 30
High urine WBC (n=22, n=81) 12 39
High urine RBC (n=16, n=66) 1 27
High leukocyte esterase (n=19, n=67) 6 18
64.Secondary Outcome
Title LTE: Mean Seated Systolic Blood Pressure (SBP) During LTE
Hide Description During LTE, blood pressure was taken in participants while seated, measured in millimeters of mercury (mmHg) and were assessed at all office visits prior to SC injection of abatacept. Vital signs were also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Time Frame Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261,1345, 1457,1541,1625,1709,1821,1905,1989,2073
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in LTE period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point.
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 35 110
Mean (Standard Deviation)
Unit of Measure: mm Hg
Day 337 (n=35, n=110) 125.7  (13.76) 120.8  (15.92)
Day 365 (n=32, n=108) 122.7  (14.26) 120.4  (15.11)
Day 449 (n=32, n=108) 122.9  (15.08) 119.5  (14.88)
Day 533 (n=32, n=108) 123.0  (14.48) 120.7  (15.75)
Day 617 (n= 30, n=107) 121.7  (13.26) 118.7  (15.30)
Day 729 (n=30, n=106) 122.2  (11.77) 121.5  (17.41)
Day 813 (n=30, n=101) 126.6  (12.66) 120.6  (15.65)
Day 897 (n=30, n=102) 123.9  (11.92) 122.5  (14.92)
Day 981 (n=28, n=100) 123.3  (12.23) 122.9  (15.03)
Day 1093 (n=26, n=99) 127.2  (18.41) 123.7  (15.11)
Day 1177 (n=25, n=96) 125.8  (11.17) 123.0  (15.96)
Day 1261 (n=25, n=92) 124.9  (11.04) 119.7  (13.64)
Day 1345 (n=24, n=82) 124.5  (13.11) 121.9  (14.49)
Day 1457 (n=21, n=79) 124.1  (14.75) 125.5  (18.41)
Day 1541 (n=21, n=79) 126.1  (15.06) 122.3  (14.53)
Day 1625 (n=21, n=77) 122.4  (9.09) 120.3  (13.76)
Day 1709 (n=21, n=74) 123.0  (13.08) 121.9  (14.90)
Day 1821 (n=20, n=33) 125.4  (13.22) 124.3  (10.95)
Day 1905 (n=18, n=0) 121.8  (13.14) NA [1]   (NA)
Day 1989 (n=13, n=0) 124.6  (9.56) NA [1]   (NA)
Day 2073 (n=1, n=0) 113.0  (0) NA [1]   (NA)
[1]
No participants; n=0
65.Secondary Outcome
Title LTE: Mean Seated Diastolic Blood Pressure (DBP) During LTE
Hide Description During LTE, blood pressure was taken in participants while seated, measured in millimeters of mercury (mmHg) and were assessed at all office visits prior to SC injection of abatacept. Vital signs were also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Time Frame Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in LTE period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point.
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 35 110
Mean (Standard Deviation)
Unit of Measure: mmHg
Day 337 (n=35, 110) 76.3  (6.69) 75.4  (11.18)
Day 365 (n=32, 108) 75.1  (10.42) 75.1  (8.94)
Day 449 (n=32, n=108) 77.3  (9.48) 73.8  (9.12)
Day 533 (n=32, n=108) 75.5  (8.43) 75.4  (9.14)
Day 617 (n=30, n=107) 74.2  (8.81) 74.8  (9.45)
Day 729 (n=30, n=106) 73.2  (8.42) 76.1  (9.86)
Day 813 (n=30, n=101) 75.7  (9.39) 76.4  (9.30)
Day 897 (n=30, n=102) 76.8  (8.41) 75.5  (9.09)
Day 981 (n=28, n=100) 77.4  (6.55) 76.1  (9.67)
Day 1093 (n=26, n=99) 76.7  (7.11) 75.9  (9.88)
Day 1177 (n=25, n=96) 76.3  (6.32) 75.9  (8.58)
Day 1261 (n=25, n=92) 75.4  (8.18) 75.6  (8.59)
Day 1345 (n=24, n=82) 75.3  (6.08) 75.6  (9.03)
Day 1457 (n=21, n=79) 75.6  (9.18) 77.1  (10.04)
Day 1541 (n=21, n=79) 76.9  (8.14) 76.0  (9.15)
Day 1625 (n=21, n=77) 77.2  (5.89) 74.9  (9.01)
Day 1709 (n=21, n=74) 75.0  (9.47) 75.4  (9.09)
Day1821 (n=20, n=33) 76.0  (7.99) 78.3  (7.57)
Day 1905 (n=18, n=0) 73.2  (7.96) NA [1]   (NA)
Day 1989 (n=13, n=0) 77.0  (5.31) NA [1]   (NA)
Day 2073 (n=1, n=0) 69.0  (0) NA [1]   (NA)
[1]
No participants; n=0
66.Secondary Outcome
Title LTE: Mean Heart Rate (HR) During LTE
Hide Description During LTE, heart rate was taken in participants while seated, measured in beats per minute (bpm) and was assessed at all office visits prior to SC injection of abatacept. Heart rate was also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Time Frame Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in LTE period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point.
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 35 110
Mean (Standard Deviation)
Unit of Measure: bpm
Day 337 (n=35, n=110) 74.3  (7.07) 74.9  (8.76)
Day 365 (n=32, n=109) 74.2  (7.76) 75.7  (8.45)
Day 449 (n=32, n=108) 74.4  (6.62) 75.7  (7.76)
Day 533 (n=32, n=108) 75.8  (6.62) 74.7  (8.32)
Day 617 (n=30, n=107) 75.7  (6.96) 76.0  (8.35)
Day 729 (n=30, n=106) 74.2  (8.60) 75.1  (8.70)
Day 813 (n=30, n=103) 72.4  (7.57) 76.2  (9.23)
Day 897 (n=30, n=102) 76.1  (7.71) 76.3  (8.15)
Day 981 (n=28, n=100) 74.4  (8.00) 76.5  (10.75)
Day 1093 (n=26, n=99) 76.3  (8.35) 75.0  (9.20)
Day 1177 (n=25, n=97) 77.6  (6.89) 75.3  (9.00)
Day 1261 (n=25, n=92) 75.7  (7.97) 74.4  (8.91)
Day 1345 (n=24, n=82) 73.5  (8.54) 73.6  (8.62)
Day 1457 (n=21, n=79) 75.0  (7.67) 76.8  (7.96)
Day 1541 (n=21, n=79) 77.3  (7.34) 75.1  (8.51)
Day 1625 (n=21, n=77) 76.9  (7.77) 75.2  (8.12)
Day 1709 (n=21, n=74) 78.7  (6.86) 74.7  (8.83)
Day 1821 (n=20, n=33) 79.5  (7.80) 78.2  (6.78)
Day 1905 (n=18, n=0) 77.1  (8.97) NA [1]   (NA)
Day 1989 (n= 13, n=0) 77.2  (9.53) NA [1]   (NA)
Day 2073 (n=1, n=0) 63.0  (0) NA [1]   (NA)
[1]
No participants; n=0
67.Secondary Outcome
Title LTE: Mean Temperature (T) During LTE
Hide Description During LTE, temperature was taken in participants while seated, measured in degrees celsius and was assessed at all office visits prior to SC injection of abatacept. Temperature was also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Time Frame Days 337, 365, 449,533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication in LTE period. N=Number of Participants Analyzed. n (when indicated)= number of participants with data available at that time point.
Arm/Group Title LTE Abatacept for LI Period 1 Non-responders LTE Abatacept for Short Term Completers
Hide Arm/Group Description:
Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 and weekly for 12 weeks (ie, participants did not enter DBW or RI periods). If clinical response was achieved, participant continued in LTE until SC administration of Abatacept was approved by the respective country and commercially available or until sponsor elected to terminate the study.
Participant’s who successfully completed the Short Term of the study, entered the LTE on Day 253 and received weekly open-label SC abatacept (125 mg) in the LTE until SC administration of ABA was approved by the respective country and commercially available or until the sponsor elected to terminate the study. Participants who completed the ST study (Completers) had received ABA during LI Period 1, entered DBW Period 2 (ABA or PLA), and in RI Period 3 continued/switched to ABA (with either ABA or PLA IV loading dose, as appropriate).
Overall Number of Participants Analyzed 35 110
Mean (Standard Deviation)
Unit of Measure: degrees Celsius
Day 337 (n=35, n=110) 36.29  (0.285) 36.31  (0.370)
Day 365 (n=32, n=108) 36.35  (0.370) 36.30  (0.393)
Day 449 (n=32, n=108) 36.40  (0.354) 36.30  (0.294)
Day 533 (n=32, n=108) 36.42  (0.358) 36.30  (0.312)
Day 617 (n=30, n=106) 36.38  (0.248) 36.37  (0.316)
Day 729 (n=30, n=106) 36.47  (0.252) 36.27  (0.332)
Day 813 (n=30, n=103) 36.49  (0.284) 36.30  (0.324)
Day 897 (n=30, n=102) 36.44  (0.254) 36.26  (0.325)
Day 981 (n=28, n=100) 36.48  (0.259) 36.30  (0.295)
Day 1093 (n=26, n=99) 36.35  (0.370) 36.28  (0.278)
Day 1177 (n=25, n=97) 36.41  (0.277) 36.24  (0.327)
Day 1261 (n=25, n=92) 36.39  (0.256) 36.24  (0.276)
Day 1345 (n=24,n=82) 36.29  (0.285) 36.23  (0.232)
Day 1457 (n=21, n=79) 36.32  (0.253) 36.23  (0.242)
Day 1541 (n=21, n=79) 36.34  (0.223) 36.24  (0.198)
Day 1625 (n=21, n=77) 36.37  (0.215) 36.20  (0.214)
Day 1709 (n=21, n=74) 36.35  (0.178) 36.24  (0.249)
Day 1821 (n=20, n=33) 36.25  (0.315) 36.26  (0.228)
Day 1905 (n=18, n=0) 36.37  (0.211) NA [1]   (NA)
Day 1989 (n=13, n=0) 36.35  (0.139) NA [1]   (NA)
Day 2073 (n=1, n=0) 36.40  (0) NA [1]   (NA)
[1]
No participants; n=0
Time Frame Day 1 up to 56 days post last dose, through LTE (for those participating in LTE); Day 1 up to 56 days post last dose until final day of study for Period 1 non-completers.
Adverse Event Reporting Description Study initiated November 2007 and LTE ended February 2014. Periods 1, 2, 3 were each 12 weeks in length. LTE started Day 253 and continued until abatacept was approved by the respective country and commercially available or until the sponsor elected to terminate the study.
 
Arm/Group Title Period 1 Non-Completers Period 1 Non-Responders Abatacept Received in Period 2 Placebo Received in Period 2
Hide Arm/Group Description Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. These participants did not complete the Period and did not continue in the study. Participants received Abatacept SC injections (fixed dose of 125 mg) during Lead-in (LI) Period 1 for 12 weeks. If after 12 weeks the participant was a non-responder (unable to achieve DAS28-CRP decrease by ≥ 0.6 from Day 1), they directly entered the LTE receiving open label Abatacept SC injections (125 mg) starting on Day 85 until completion of the LTE. Participants who responded to abatacept in Period 1, entered Period 2 and were randomized to receive Abatacept SC injections (fixed dose of 125 mg) starting on Day 85 and weekly for 12 weeks. Abatacept SC injections of 125 mg were continued in Reintroduction Period 3 and during the LTE Period until completion of the LTE. Participants who responded to abatacept in Period 1, entered Period 2 and were randomized to receive Placebo SC injections starting on Day 85 and weekly for 12 weeks. Abatacept SC injections of 125 mg were administered during Reintroduction Period 3 and during the LTE Period until completion of the LTE.
All-Cause Mortality
Period 1 Non-Completers Period 1 Non-Responders Abatacept Received in Period 2 Placebo Received in Period 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Period 1 Non-Completers Period 1 Non-Responders Abatacept Received in Period 2 Placebo Received in Period 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/10 (20.00%)   12/37 (32.43%)   11/40 (27.50%)   27/80 (33.75%) 
Cardiac disorders         
Myocardial ischaemia  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  0/80 (0.00%) 
Cardiac failure acute  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  0/80 (0.00%) 
Acute coronary syndrome  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  1/80 (1.25%) 
Atrial fibrillation  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  0/80 (0.00%) 
Cardiac arrest  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Arrhythmia  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Myocardial infarction  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Gastrointestinal disorders         
Peptic ulcer  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  0/80 (0.00%) 
Rectal fissure  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Upper gastrointestinal haemorrhage  1  0/10 (0.00%)  1/37 (2.70%)  0/40 (0.00%)  0/80 (0.00%) 
Hiatus hernia  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  0/80 (0.00%) 
Gastritis  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
General disorders         
Sudden death  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Chest pain  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Fatigue  1  0/10 (0.00%)  1/37 (2.70%)  0/40 (0.00%)  0/80 (0.00%) 
Hepatobiliary disorders         
Cholelithiasis  1  1/10 (10.00%)  0/37 (0.00%)  1/40 (2.50%)  0/80 (0.00%) 
Infections and infestations         
Pneumonia  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  1/80 (1.25%) 
Cellulitis  1  1/10 (10.00%)  1/37 (2.70%)  0/40 (0.00%)  0/80 (0.00%) 
Respiratory tract infection  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Injury, poisoning and procedural complications         
Tendon rupture  1  0/10 (0.00%)  1/37 (2.70%)  0/40 (0.00%)  0/80 (0.00%) 
Incisional hernia  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Pelvic fracture  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Ulna fracture  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Upper limb fracture  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Laceration  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Ankle fracture  1  0/10 (0.00%)  1/37 (2.70%)  0/40 (0.00%)  0/80 (0.00%) 
Fall  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Hip fracture  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  0/80 (0.00%) 
Animal bite  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Musculoskeletal and connective tissue disorders         
Arthritis  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  0/80 (0.00%) 
Vertebral foraminal stenosis  1  0/10 (0.00%)  1/37 (2.70%)  0/40 (0.00%)  0/80 (0.00%) 
Spinal osteoarthritis  1  0/10 (0.00%)  1/37 (2.70%)  0/40 (0.00%)  0/80 (0.00%) 
Rheumatoid arthritis  1  0/10 (0.00%)  1/37 (2.70%)  0/40 (0.00%)  2/80 (2.50%) 
Back pain  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  2/80 (2.50%) 
Neck pain  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Intervertebral disc degeneration  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  0/80 (0.00%) 
Osteoarthritis  1  0/10 (0.00%)  2/37 (5.41%)  0/40 (0.00%)  3/80 (3.75%) 
Pseudarthrosis  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  0/80 (0.00%) 
Rotator cuff syndrome  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  1/80 (1.25%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Squamous cell carcinoma  1  0/10 (0.00%)  1/37 (2.70%)  0/40 (0.00%)  0/80 (0.00%) 
Adenoma benign  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Breast cancer  1  0/10 (0.00%)  0/37 (0.00%)  1/40 (2.50%)  0/80 (0.00%) 
Malignant melanoma  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Lung adenocarcinoma  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Renal and urinary disorders         
Renal colic  1  0/10 (0.00%)  1/37 (2.70%)  0/40 (0.00%)  0/80 (0.00%) 
Stress urinary incontinence  1  0/10 (0.00%)  1/37 (2.70%)  0/40 (0.00%)  0/80 (0.00%) 
Urinary retention  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Lupus nephritis  1  0/10 (0.00%)  1/37 (2.70%)  0/40 (0.00%)  0/80 (0.00%) 
Reproductive system and breast disorders         
Benign prostatic hyperplasia  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%) 
Respiratory, thoracic and mediastinal disorders         
Respiratory failure  1  0/10 (0.00%)  0/37 (0.00%)  0/40 (0.00%)  1/80 (1.25%)