Phase 3
Completed N=391
Phase III Study of BMS-188667 (CTLA4Ig) in Patients With Rheumatoid Arthritis Who Are Currently Failing Anti-TNF Therapy or Who Have Failed Anti-TNF Therapy in the Past.
Source: ClinicalTrials.gov NCT00048581 ↗Enrolled (actual)
391
Serious AEs
25.4%
Results posted
Jun 2011
Primary outcomePrimary: Double-blind Period (DB); Number of Participants With American College of Rheumatology (ACR) 20 Response at Day 169 — 129; 26 participants — p=<0.001
Summary
The purpose of this clinical research study is to determine whether abatacept treatment on a background of Disease Modifying Antirheumatic Drugs (DMARDs) will relieve the symptoms of rheumatoid arthritis (RA) in participants who are currently receiving anti-tumor necrosis factor (TNF) therapy for at least 3 months and are not responding or have taken anti-TNF therapy in the last 3 months and did not respond. The safety of treatment with abatacept will also be evaluated. This study also has a 4.5-year long-term extension beginning 6 months after the start of the study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Double-blind Period (DB); Number of Participants With American College of Rheumatology (ACR) 20 Response at Day 169 |
129; 26 | <0.001 sig |
| PRIMARY DB; Number of Participants Achieving Clinically Meaningful Improvement in Health Assessment Questionnaire (HAQ) |
121; 31 | <0.001 sig |
| PRIMARY Open-Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation |
6; 136; 24; 20; 302; 192 | — |
| PRIMARY OL; Number of Participants AEs of Special Interest |
254; 42; 21; 17; 65; 22 | — |
| PRIMARY OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria |
12; 18; 9; 8; 1; 6 | — |
| PRIMARY OL; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality Criteria |
3; 12; 12; 30; 2; 20 | — |
| PRIMARY OL; Mean Time-matched Baseline Immunoglobulin (Ig) Levels Over the OL |
327.9; 326.9; 1346.0; 1364.0; 180.1; 160.1 | — |
| PRIMARY OL; Mean Time-matched Change From Baseline in Immunoglobulin (Ig) Levels Over the OL |
-35.3; 1.10; -233.0; -72.8; -17.8; -5.42 | — |
| SECONDARY DB; Number of Participants With ACR 20, ACR 50, and ACR 70 Responses Over Time |
45; 7; 6; 0; 2; 0 | 0.001 sig |
| SECONDARY DB; Mean Time-matched Baseline Tender Joint Counts (TJCs) and Post-Baseline TJCs Over Time: ACR Core Component |
31.33; 32.75; 25.58; 30.35; 31.41; 32.72 | — |
| SECONDARY DB; Mean Time-Matched Percentage of Change From Baseline in TJC Over Time: ACR Core Component |
19.74; 6.43; 32.68; 14.96; 40.52; 24.99 | — |
| SECONDARY DB; Mean Time-matched Baseline Swollen Joint Count (SJC) and Post-Baseline SJCs Over Time: ACR Core Component |
22.31; 22.00; 17.88; 19.06; 22.49; 21.86 | — |
| SECONDARY DB; Mean Time-Matched Percentage of Change From Baseline in SJC Over Time: ACR Core Component |
18.64; 13.13; 32.68; 14.96; 38.49; 24.98 | — |
| SECONDARY DB; Mean Time-matched Baseline Participant Pain Assessment Over Time: ACR Core Component |
71.09; 69.20; 61.05; 67.65; 70.45; 69.80 | — |
| SECONDARY DB; Mean Time-Matched Percentage of Change From Baseline in Participant Pain Assessment Over Time: ACR Core Component |
8.48; -3.19; 18.31; 8.36; 24.58; 16.65 | — |
| SECONDARY DB; Mean Time-matched Baseline HAQ-DI Over Time: ACR Core Component |
1.84; 1.86; 1.69; 1.83; 1.84; 1.85 | — |
| SECONDARY DB; Mean Time-Matched Percentage of Change From Baseline in HAQ-DI Over Time: ACR Core Component |
7.94; -1.10; 13.75; 6.79; 19.05; 9.61 | — |
| SECONDARY DB; Mean Time-matched Baseline Participant Global Assessment Over Time: ACR Core Component |
69.30; 68.93; 58.55; 65.15; 68.86; 69.33 | — |
| SECONDARY DB; Mean Time-Matched Percentage of Change From Baseline in Participant Global Assessment Over Time: ACR Core Component |
11.54; -3.18; 18.31; 2.13; 29.84; 10.94 | — |
| SECONDARY DB; Mean Time-matched Baseline Physician Global Assessment Over Time: ACR Core Component |
68.86; 66.91; 54.07; 61.43; 68.73; 66.81 | — |
| SECONDARY DB; Mean Time-Matched Percentage of Change From Baseline in Physician Global Assessment Over Time: ACR Core Component |
19.27; 6.26; 32.32; 18.00; 38.41; 25.51 | — |
| SECONDARY DB; Mean Time-matched Baseline C-Reactive Protein (CRP) Levels Over Time: ACR Core Component |
4.53; 3.97; 3.20; 4.01; 4.62; 4.03 | — |
| SECONDARY DB; Mean Time-Matched Percentage of Change From Baseline in CRP Levels Over Time: ACR Core Component |
14.03; -20.8; 24.05; -20.1; 22.83; -14.8 | — |
| SECONDARY DB; Mean Baseline Levels of Disease Biomarkers (Interleukin-6 (IL-6), Soluble IL-2 Receptor [sIL-2R], and Tumor Necrosing Factor [TNF]-Alpha) in Participants With Measurements at Day 169 |
46.19; 43.18; 1840; 1879; 35.24; 30.64 | — |
| SECONDARY DB; Mean Change From Baseline to Day 169 in Levels of Disease Biomarkers (IL-6, sIL-2R, and TNF-alpha) in Participants With Measurements at Day 169 |
-24.4; 4.71; -565; -36.1; -13.5; 5.87 | — |
| SECONDARY DB; Mean Baseline Levels of Disease Biomarkers (E-Selectin, Soluble Inter-Cellular Adhesion Molecule 1 [sICAM-1], and Matrix Metalloproteinase-3 [MMP-3]) in Participants With Measurements at Day 169 |
93.03; 84.53; 426.6; 443.5; 86.53; 84.18 | — |
| SECONDARY DB; Mean Change From Baseline to Day 169 in Levels of Disease Biomarkers (E-Selectin, sICAM-1, and MMP-3) in Participants With Measurements at Day 169 |
-10.6; 6.54; -22.2; -29.5; -37.0; -9.62 | — |
| SECONDARY DB; Mean Change From Baseline to Day 169 in Rheumatoid Factor (RF) Status |
46; 25; 3; 3; 154; 73 | — |
| SECONDARY DB; Mean Baseline Short Form 36 (SF-36) Quality of Life Physical Component Summary (PCS), Mental Component Summary (MCS), and SF-36 Individual Component Scores For Participants With Measurements at Day 85 |
27.41; 27.77; 41.13; 43.00; 25.94; 26.31 | — |
| SECONDARY DB; Adjusted Mean Change From Baseline to Day 85 in Short SF-36 PCS, MCS, and SF-36 Individual Component Scores |
5.76; 2.12; 4.64; 2.08; 3.97; 2.27 | <0.001 sig |
| SECONDARY DB; Mean Baseline SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participants With Measurements at Day 169 |
27.36; 27.75; 41.56; 42.98; 25.96; 26.24 | — |
| SECONDARY DB; Adjusted Mean Change From Baseline to Day 169 in SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participants With Measurements at Day 169 |
6.58; 1.12; 5.15; 2.11; 5.30; 1.27 | <0.001 sig |
| SECONDARY DB; Mean Baseline HAQ-DI and HAQ Component Scores in Participants With Assessments at Day 169 |
1.83; 1.82; 1.64; 1.54; 1.42; 1.43 | — |
| SECONDARY DB; Adjusted Mean Change From Baseline to Day 169 in HAQ-DI and HAQ Component Scores in Participants With Assessments at Day 169 |
-0.45; -0.11; -0.58; -0.26; -0.61; -0.29 | <0.001 sig |
| SECONDARY DB; Mean Disease Activity Score (DAS)28 (C-Reactive Protein [CRP]) and Mean Disease Activity Score (Erythrocyte Sedimentation Rate [ESR]) at Day 169 |
6.53; 6.51; 4.70; 5.78; 6.88; 6.88 | — |
| SECONDARY DB; Adjusted Mean Change From Baseline to Day 169 in DAS28 (CRP) and DAS28 (ESR) |
-1.83; -0.74; -1.98; -0.71 | — |
| SECONDARY DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation |
1; 0; 27; 15; 7; 1 | — |
| SECONDARY DB; Number of Participants AEs of Special Interest |
97; 43; 7; 1; 4; 0 | — |
| SECONDARY DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality (MA) Criteria |
0; 1; 0; 1; 0; 0 | — |
| SECONDARY DB; Number of Participants With Blood Chemistry Laboratories Meeting MA Criteria |
0; 0; 2; 2; 4; 1 | — |
| SECONDARY DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA) |
1; 2; 3 | — |
| SECONDARY OL; Number of Participants With ACR 20, ACR 50, and ACR 70 Responses Over Time For Participants Treated in the OL |
43; 6; 5; 0; 1; 0 | — |
| SECONDARY OL; Number of Participants With Low Disease Activity (LDAS) or Remission For Participants Treated in the OL |
5; 0; 1; 0; 10; 1 | — |
| SECONDARY OL; Mean Time-matched Baseline DAS28 (CRP) Over Time For Participants Treated in the OL |
6.52; 6.46; 6.53; 6.46; 6.51; 6.43 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in DAS28 (CRP) Over Time For Participants Treated in the OL |
-0.74; -0.40; -1.15; -0.72; -1.59; -1.05 | — |
| SECONDARY OL; Mean Time-matched Baseline DAS28 (ESR) Over Time For Participants Treated in the OL |
6.89; 6.83; 6.87; 6.85; 6.91; 6.80 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in DAS28 (ESR) Over Time For Participants Treated in the OL |
-2.05; -0.83; -2.09; -2.00; -2.31; -2.05 | — |
| SECONDARY OL; Number of Participants Achieving HAQ Response Over Time In Participants Treated in the OL |
59; 16; 82; 30; 101; 34 | — |
| SECONDARY OL; Mean Time-matched Baseline HAQ-DI and HAQ Component Scores Over Time For Participants Treated in the OL |
1.82; 1.79; 1.65; 1.54; 1.41; 1.44 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in HAQ-DI and HAQ Component Scores For Participants Treated in the OL |
-0.51; -0.16; -0.60; -0.26; -0.61; -0.31 | — |
| SECONDARY OL; Mean Time-matched Baseline Levels of Rheumatoid Factor (RF) Over Time For Participants Treated in the OL |
262.4; 264.8; 275.5; 270.4; 276.8; 301.5 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in Levels of RF Over Time For Participants Treated in the OL |
-80.4; -25.1; -50.0; -69.6; -30.2; -82.8 | — |
| SECONDARY OL; Mean Time-matched Baseline Levels of C-Reactive Protein (CRP) Over Time For Participants Treated in the OL |
46.00; 33.34; 45.62; 34.05; 45.61; 34.60 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in Levels of CRP Over Time For Participants Treated in the OL |
-25.3; -0.36; -29.1; -16.8; -29.4; -10.8 | — |
| SECONDARY OL; Mean Time-matched Baseline Erythrocyte Sedimentation Rate (ESR) Over Time For Participants Treated in the OL |
50.60; 44.40; 50.51; 44.10; 50.53; 42.06 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in ESR Over Time For Participants Treated in the OL |
-18.0; -0.44; -18.8; -10.1; -20.2; -6.25 | — |
| SECONDARY OL; Mean Time-matched Baseline Levels of Soluble Interleukin 2 Receptor (sIL-2R) Over Time For Participants Treated in the OL |
1879.0; 1805.0; 1851.0; 1800.0; 1942.0; 1708.0 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in Levels of sIL-2R Over Time For Participants Treated in the OL |
-590.0; -19.6; -522.0; -424.0; -836.0; -483.0 | — |
| SECONDARY OL; Mean Time-matched Baseline SF-36 PCS and MCS Over Time For Participants Treated in OL |
27.52; 28.07; 27.70; 27.92; 27.81; 28.65 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in SF-36 PCS and MCS Over Time For Participants Treated in OL |
7.46; 1.90; 8.30; 6.21; 10.28; 6.79 | — |
| SECONDARY OL; Mean Time-matched Baseline Physical Function Score Over Time For Participants Treated in the OL |
26.22; 26.60; 26.37; 26.49; 27.03; 26.66 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in Physical Function Score Over Time For Participants Treated in the OL |
5.75; 1.82; 7.14; 4.80; 7.61; 7.38 | — |
| SECONDARY OL; Mean Time-matched Baseline Role-Physical Score Over Time For Participants Treated in the OL |
30.50; 32.36; 30.49; 32.40; 30.48; 32.45 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in Role-Physical Score Over Time For Participants Treated in the OL |
7.82; 1.30; 7.78; 6.49; 10.76; 6.59 | — |
| SECONDARY OL; Mean Time-matched Baseline Bodily Pain Score Over Time For Participants Treated in the OL |
30.76; 31.90; 30.75; 31.84; 31.00; 31.98 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in Bodily Pain Score Over Time For Participants Treated in the OL |
9.59; 3.32; 10.25; 9.55; 12.36; 10.29 | — |
| SECONDARY OL; Mean Time-matched Baseline General Health Score Over Time For Participants Treated in the OL |
35.28; 35.52; 35.50; 35.48; 35.49; 35.48 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in General Health Score Over Time For Participants Treated in the OL |
4.48; 1.09; 4.36; 4.04; 6.43; 5.85 | — |
| SECONDARY OL; Mean Time-matched Baseline Vitality Score Over Time For Participants Treated in the OL |
35.06; 36.51; 35.09; 36.65; 35.45; 36.50 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in Vitality Score Over Time For Participants Treated in the OL |
7.80; 2.89; 8.00; 6.69; 8.49; 7.52 | — |
| SECONDARY OL; Mean Time-matched Baseline Social Functioning Score Over Time For Participants Treated in the OL |
33.31; 34.37; 33.59; 34.30; 33.87; 34.32 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in Social Functioning Score Over Time For Participants Treated in the OL |
8.36; 2.99; 8.17; 7.22; 9.89; 9.10 | — |
| SECONDARY OL; Mean Time-matched Baseline Role-Emotional Score Over Time For Participants Treated in the OL |
35.73; 37.60; 35.93; 37.75; 36.09; 35.86 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in Role-Emotional Score Over Time For Participants Treated in the OL |
7.17; 1.83; 5.47; 6.52; 7.29; 10.39 | — |
| SECONDARY OL; Mean Time-matched Baseline Mental Health Score Over Time For Participants Treated in the OL |
40.96; 43.47; 41.11; 43.53; 41.85; 42.69 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in Mental Health Score Over Time For Participants Treated in the OL |
4.42; 1.65; 4.53; 4.29; 5.54; 7.19 | — |
| SECONDARY OL; Mean Time-matched Baseline Medical Outcomes Study Sleep Module (MOS-sleep) Score Over Time For Participants Treated in the OL |
49.18; 45.49; 48.87; 45.54; 48.62; 45.36 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in MOS-Sleep Score Over Time For Participants Treated in the OL |
-11.1; -4.31; -11.2; -10.4; -12.5; -11.9 | — |
| SECONDARY OL; Mean Time-matched Baseline Fatigue Visual Analog Score (VAS) Over Time For Participants Treated in the OL |
73.73; 71.24; 73.54; 70.78; 73.75; 69.59 | — |
| SECONDARY OL; Mean Time-matched Change From Baseline in Fatigue VAS Over Time For Participants Treated in the OL |
-25.0; -7.28; -26.1; -21.8; -28.2; -22.2 | — |
| SECONDARY OL; Mean Time-matched Baseline Activity Limitation Score Over Time For Participants Treated in the OL |
17.18; 15.01; 16.97; 15.70; 16.59; 14.56 | — |
| SECONDARY OL; Mean Change From Baseline in Activity Limitation Score Over Time For Participants Treated in the OL |
-7.80; -1.78; -8.04; -6.08; -8.29; -8.32 | — |
| SECONDARY Cumulative Analysis (DB + OL); Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbent Assay (ELISA) |
22; 5; 26 | — |
Eligibility Criteria
Eligibility Criteria:
- Active rheumatoid arthritis currently failing anti-TNF therapy or have failed anti-TNF therapy in the past.
Exclusion Criteria
- Women who are pregnant or breast feeding
- Current symptoms of serious medical disease
- History of cancer in last 5 years other than non-melanoma skin cancer
- Chronic serious infection
- Active TB requiring treatment in last 5 years
- Herpes zoster in last 2 months
- Any active viral infection including Human Immunodeficiency Virus (HIV)
- Serious side effects associated with previous anti-TNF therapy
Data sourced from ClinicalTrials.gov (NCT00048581). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.