Phase 3
Completed N=167
Phase IIIB Subcutaneous Missed Dose Study
Source: ClinicalTrials.gov NCT00533897 ↗Enrolled (actual)
167
Serious AEs
31.1%
Results posted
Jun 2011
Primary outcomePrimary: 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 — 0; 1.4; 0; 8.2 percentage of participants — p=0.119
Summary
The purpose of the study is to determine whether subcutaneous abatacept administered to patients with rheumatoid arthritis is associated with increased immunogenicity or increased safety events upon withdrawal and reintroduction.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
0; 1.4; 0; 8.2; 0; 9.6 | 0.119 |
| PRIMARY 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 |
0; 0; 2.6; 2.7; 2.6; 2.7 | — |
| SECONDARY RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Day 253, by DBW Period Placebo Group |
0; 0; 0; 4.9; 0; 4.9 | — |
| SECONDARY Lead-in (LI) Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time |
1.2; 0; 1.2; 0; 0; 0 | — |
| SECONDARY LI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by Electrochemiluminescence (ECL) Over Time |
1.2; 0; 1.2; 0; 0; 0 | — |
| SECONDARY DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time |
0; 1.3; 0; 7.5; 0; 8.8 | — |
| SECONDARY DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Post Visits |
— | — |
| SECONDARY DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL Over Time |
0; 6.3; 0; 3.8; 0; 10.0 | — |
| SECONDARY DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL At Post Visits |
— | — |
| SECONDARY RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time by DBW Treatment Group |
2.6; 1.3; 5.0; 3.8; 7.5; 5.1 | — |
| SECONDARY RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL Over Time by DBW Treatment Group |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Short Term (ST); Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 ELISA Antibody Responses by DBW Treatment Groups |
7.7; 1.3; 5.0; 8.8; 12.5; 10.0 | — |
| SECONDARY Short Term: Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 ECL Antibody Responses by DBW Treatment Groups |
0; 7.5; 0; 3.8; 0; 10.0 | — |
| SECONDARY Short Term: Mean Change in Disease Activity Score (DAS) 28 (Using C-Reactive Protein [CRP]) From Baseline Over Time by DBW Treatment Groups |
-0.64; -0.87; -1.07; -1.10; -1.39; -1.62 | — |
| SECONDARY 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 |
80; 76.9; 67.5; 62.8; 35.0; 37.2 | — |
| SECONDARY Short Term; Mean Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline Over Time by DBW Treatment Groups |
-0.31; -0.30; -0.46; -0.35; -0.58; -0.51 | — |
| SECONDARY Short Term; Percentage of Participants With HAQ-DI Response Over Time by DBW Treatment Groups |
47.5; 42.9; 62.5; 52.5; 67.5; 62.0 | — |
| SECONDARY LI; Mean Change in DAS 28 (CRP) From Baseline Over Time |
-0.72; -1.00; -1.35; -1.39; -1.53 | — |
| SECONDARY LI; Percentage of Participants With Clinically Meaningful Improvement in DAS (CRP) Over Time |
26.0; 40.6; 56.1; 59.4; 64.6 | — |
| SECONDARY DBW Period; Mean Change in DAS 28 (CRP) From DBW Period Baseline (Day 85) Over Time |
0.19; 0.16; 0.14; 0.35; -0.06; 0.40 | — |
| SECONDARY DBW Period; Percentage of Participants With Rheumatoid Arthritis (RA) Flare Over Time |
0; 1.5; 9.1; 2.6; 6.3; 6.8 | — |
| SECONDARY RI Period; Mean Change in DAS 28 (CRP) From RI Period Baseline (Day 169) Over Time |
-0.26; -0.56; -0.50; -0.31; -0.59; -0.66 | — |
| SECONDARY LI; Number of Participants With Deaths, Serious Adverse Events (SAEs), SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation |
1; 3; 0; 1; 82; 29 | — |
| SECONDARY LI Period; Number of Participants With AEs of Special Interest |
42; 0; 0; 1; 2; 2 | — |
| SECONDARY LI; Number of Participants With Hematology Values Meeting the Marked Abnormality (MA) Criteria |
0; 0; 1; 1; 0; 3 | — |
| SECONDARY LI; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria |
0; 1; 2; 0; 0; 1 | — |
| SECONDARY LI; Number of Participants With Electrolyte Values Meeting the Marked Abnormality Criteria |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY LI; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria |
9; 4; 3; 0; 1; 1 | — |
| SECONDARY LI Period; Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
125.0; 122.3; 122.0; 121.4; 120.3; 122.0 | — |
| SECONDARY LI Period; Mean Heart Rate (HR) |
73.9; 76.0; 75.5; 75.5; 75.1; 74.7 | — |
| SECONDARY LI Period; Mean Temperature (T) |
36.39; 36.34; 36.39; 36.38; 36.33; 36.35 | — |
| SECONDARY DBW; Number of Participants With Death, Serious SAEs, Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation |
0; 2; 0; 2; 0; 0 | — |
| SECONDARY DBW; Number of Participants With AEs of Special Interest |
5; 7; 0; 0; 0; 0 | — |
| SECONDARY DBW; Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY DBW; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria |
0; 0; 0; 0; 1; 0 | — |
| SECONDARY DBW; Number of Participants With Electrolytes Values Meeting the Marked Abnormality Criteria |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY DBW; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria |
2; 5; 1; 3; 0; 1 | — |
| SECONDARY DBW; Mean Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During Double Blind Period |
119.4; 120.4; 120.3; 121.2; 119.6; 119.4 | — |
| SECONDARY DBW Period; Mean Heart Rate (HR) During Period 2 |
75.8; 73.9; 75.9; 74.5; 73.8; 74.2 | — |
| SECONDARY DBW Period; Mean Temperature (T) During Period II |
36.34; 36.44; 36.31; 36.36; 36.38; 36.32 | — |
| SECONDARY RI; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation |
0; 0; 0; 0; 0; 1 | — |
| SECONDARY RI; Number of Participants With AEs of Special Interest |
7; 8; 7; 0; 0; 0 | — |
| SECONDARY RI; Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY RI; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY RI; Number of Participants With Electrolytes Values Meeting the Marked Abnormality Criteria |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY RI; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria |
1; 1; 1; 0; 1; 0 | — |
| SECONDARY RI Period; Mean Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During Period III |
121.3; 116.6; 118.9; 119.1; 118.4; 121.0 | — |
| SECONDARY RI Period; Mean Heart Rate (HR) During Period III |
73.4; 73.8; 74.1; 73.1; 75.1; 70.9 | — |
| SECONDARY RI Period; Mean Temperature (T) During Period III |
36.32; 36.29; 36.26; 36.39; 36.37; 36.35 | — |
| SECONDARY Short Term; Abatacept Serum Concentration by Immunogenicity Status as Measured by ELISA by RI Treatment Groups |
39.17; 33.73; 18.05; 34.45; 35.67; 22.76 | — |
| SECONDARY Short Term; Abatacept Serum Concentration by Immunogenicity Status as Measured by ECL by RI Treatment Groups |
NA; NA; NA; 34.72; 35.61; 22.65 | — |
| SECONDARY 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 |
1; 3; 5; 10; 1; 2 | — |
| SECONDARY LTE: DAS28-CRP Mean Change From Baseline (Day 1) Over Time - All Participants Treated in LTE |
-0.48; -0.79; -0.35; -1.91; NA; -2.29 | — |
| SECONDARY LTE: Percent of Participants Who Achieved Clinical Remission in the Long Term Extension - All Participants Treated in LTE |
11.1; 36.6; NA; 59.6; 50.0; 59.3 | — |
| SECONDARY LTE: Percent of Participants With Low Disease Activity in Long Term Extension: All Participants Treated in LTE |
27.8; 66.1; NA; 75.2; 67.6; 76.1 | — |
| SECONDARY LTE: Percent of Participants With HAQ Response Over Time - All Participants Treated in LTE |
20.6; 44.5; 27.8; 56.6; 44.4; 64.3 | — |
| SECONDARY 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 |
20.1; 15.6; 7.3; 6.3; 7.8; 23.8 | — |
| SECONDARY LTE: Number of Participants With Death, Related SAEs, SAEs Leading to Discontinuation, Related AEs, or AEs Leading to Discontinuation During Long Term Extension (LTE) |
1; 6; 0; 3; 1; 5 | — |
| SECONDARY LTE: Number of Participants With AEs of Special Interest During LTE |
23; 78; 1; 3; 3; 8 | — |
| SECONDARY LTE: Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria During LTE |
1; 4; 0; 2; 0; 1 | — |
| SECONDARY LTE: Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria During LTE |
0; 3; 2; 2; 1; 8 | — |
| SECONDARY LTE: Number of Participants With Electrolyte Values Meeting the Marked Abnormality Criteria During LTE |
1; 0; 0; 3; 1; 0 | — |
| SECONDARY LTE: Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria During LTE |
6; 16; 1; 6; 4; 2 | — |
| SECONDARY LTE: Mean Seated Systolic Blood Pressure (SBP) During LTE |
125.7; 120.8; 122.7; 120.4; 122.9; 119.5 | — |
| SECONDARY LTE: Mean Seated Diastolic Blood Pressure (DBP) During LTE |
76.3; 75.4; 75.1; 75.1; 77.3; 73.8 | — |
| SECONDARY LTE: Mean Heart Rate (HR) During LTE |
74.3; 74.9; 74.2; 75.7; 74.4; 75.7 | — |
| SECONDARY LTE: Mean Temperature (T) During LTE |
36.29; 36.31; 36.35; 36.30; 36.40; 36.30 | — |
Eligibility Criteria
Inclusion Criteria
- Clinical diagnosis of Rheumatoid Arthritis
- Disease Activity Score (DAS)28-C-Reactive Protein (CRP) score ≥ 3.2 and ≤5.1
- On background methotrexate at least 3 months (≥10mg weekly)
- Must be able to self injection or allow a care giver to do it for them
- Discontinue all Biologics and Disease-Modifying Anti-rheumatic Drugs (DMARDs) except for methotrexate
Exclusion Criteria
- Participants who had prior exposure to abatacept or CTLA-4 Ig
- Received treatment with rituximab.
- Participants who have received treatment with leflunomide within 1 year of screening
- Participants who have received treatment with immunoadsorption columns (such as Prosorba columns), mycophenolate mofetil (Cellcept®), cyclosporine A or other calcineurin inhibitors, or D-Penicillamine.
Data sourced from ClinicalTrials.gov (NCT00533897). 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.