- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00533897
Phase IIIB Subcutaneous Missed Dose Study
April 22, 2015 updated by: Bristol-Myers Squibb
A Phase IIIb, Multi-Center, Randomized, Withdrawal Study to Evaluate the Immunogenicity and Safety of Subcutaneous Administered Abatacept in Adults With Active Rheumatoid Arthritis
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
270
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Cordoba, Argentina, 5000
- Local Institution
-
Santa Fe, Argentina, 3000
- Local Institution
-
-
Buenos Aires
-
Capital Federal, Buenos Aires, Argentina, 1015
- Local Institution
-
-
Santa Fe
-
Rosario, Santa Fe, Argentina, 2000
- Local Institution
-
-
-
-
Quebec
-
Trois-Rivieres, Quebec, Canada, G8Z 1Y2
- Local Institution
-
-
-
-
Distrito Federal
-
Mexico City, Distrito Federal, Mexico, 06726
- Local Institution
-
-
Estado De Mexico
-
Metepec, Estado De Mexico, Mexico, 52140
- Local Institution
-
-
Guanajuato
-
Leon, Guanajuato, Mexico, 37520
- Local Institution
-
-
Yucatan
-
Merida, Yucatan, Mexico, 97000
- Local Institution
-
-
-
-
Free State
-
Bloemfontein, Free State, South Africa, 9317
- Local Institution
-
-
Gauteng
-
Muckleneuk, Gauteng, South Africa, 0002
- Local Institution
-
Pretoria, Gauteng, South Africa, 0084
- Local Institution
-
-
Kwa Zulu Natal
-
Berea, Kwa Zulu Natal, South Africa, 4001
- Local Institution
-
-
Western Cape
-
Panorama, Western Cape, South Africa, 7500
- Local Institution
-
-
-
-
California
-
Los Angeles, California, United States, 90048
- Wallace Rheumatic Study Center
-
-
Connecticut
-
Trumbull, Connecticut, United States, 06611
- New England Research Associates, LLC
-
-
Florida
-
Sarasota, Florida, United States, 34239
- Sarasota Arthritis Research Center
-
-
Indiana
-
Indianapolis, Indiana, United States, 46227
- Diagnostic Rheumatology And Research,Pc
-
-
Maryland
-
Cumberland, Maryland, United States, 21502
- Klein And Associates, M.D., Pa
-
-
Massachusetts
-
Worcester, Massachusetts, United States, 01610
- Clinical Pharmacology Study Group
-
-
Minnesota
-
Eagan, Minnesota, United States, 55121
- St. Paul Rheumatology, P.A.
-
-
New Mexico
-
Albuquerque, New Mexico, United States, 87102
- Albuquerque Clinical Trials, Inc.
-
-
Pennsylvania
-
Bethlehem, Pennsylvania, United States, 18015
- East Penn Rheumatology Associates
-
Duncansville, Pennsylvania, United States, 16635
- Altoona Center for Clinical Research
-
Erie, Pennsylvania, United States, 16508
- Center For Assessment And Research Of Erie
-
-
South Carolina
-
Columbia, South Carolina, United States, 29204
- Columbia Arthritis Center
-
-
West Virginia
-
Clarksburg, West Virginia, United States, 26301
- Mountain State Clinical Research
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
Solution in pre-filled syringes, Subcutaneously, 0 mg, Weekly, Period II 12 weeks (Short Term)
|
Experimental: Abatacept
|
Solution in pre-filled syringes, Subcutaneously, 125 mg, Weekly, (Short Term (3 periods - 12 weeks each; Long Term)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
Time Frame: Day 169
|
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.
|
Day 169
|
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
Time Frame: Day 253 (short term)
|
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.
|
Day 253 (short term)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Day 253, by DBW Period Placebo Group
Time Frame: Day 253 (short term)
|
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.
|
Day 253 (short term)
|
Lead-in (LI) Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time
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
|
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.
|
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
|
LI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by Electrochemiluminescence (ECL) Over Time
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
|
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.
|
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
|
DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time
Time Frame: Days 86-169, includes ≤21 Days after last dose or up to 1st dose of RI Period
|
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.
|
Days 86-169, includes ≤21 Days after last dose or up to 1st dose of RI Period
|
DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Post Visits
Time Frame: Day 22 after last dose of drug to Day 85 after last dose of drug
|
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.
|
Day 22 after last dose of drug to Day 85 after last dose of drug
|
DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL Over Time
Time Frame: Days 86-169, includes ≤21 Days after last dose or up to 1st dose of RI Period
|
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.
|
Days 86-169, includes ≤21 Days after last dose or up to 1st dose of RI Period
|
DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL At Post Visits
Time Frame: Day 22 after last dose of drug to Day 85 after last dose of drug
|
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.
|
Day 22 after last dose of drug to Day 85 after last dose of drug
|
RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time by DBW Treatment Group
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
|
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.
|
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
|
RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL Over Time by DBW Treatment Group
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
|
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.
|
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
|
Short Term (ST); Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 ELISA Antibody Responses by DBW Treatment Groups
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
|
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).
|
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
|
Short Term: Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 ECL Antibody Responses by DBW Treatment Groups
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
|
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.
|
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
|
Short Term: Mean Change in Disease Activity Score (DAS) 28 (Using C-Reactive Protein [CRP]) From Baseline Over Time by DBW Treatment Groups
Time Frame: Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
|
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.
|
Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
|
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
Time Frame: Days 85, 169, and 253 (short term)
|
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.
|
Days 85, 169, and 253 (short term)
|
Short Term; Mean Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline Over Time by DBW Treatment Groups
Time Frame: Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
|
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.
|
Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
|
Short Term; Percentage of Participants With HAQ-DI Response Over Time by DBW Treatment Groups
Time Frame: Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
|
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.
|
Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
|
LI; Mean Change in DAS 28 (CRP) From Baseline Over Time
Time Frame: Days 1 (Baseline), 15, 29, 57, 78, 85
|
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.
|
Days 1 (Baseline), 15, 29, 57, 78, 85
|
LI; Percentage of Participants With Clinically Meaningful Improvement in DAS (CRP) Over Time
Time Frame: Days 15, 29, 57, 78, 85
|
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.
|
Days 15, 29, 57, 78, 85
|
DBW Period; Mean Change in DAS 28 (CRP) From DBW Period Baseline (Day 85) Over Time
Time Frame: Days 85 (Period 2 Baseline), 113, 141, and 169
|
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.
|
Days 85 (Period 2 Baseline), 113, 141, and 169
|
DBW Period; Percentage of Participants With Rheumatoid Arthritis (RA) Flare Over Time
Time Frame: Days 85, 113, 141, and 169
|
A participant had an RA flare if at least 2 of the following criteria were met:
|
Days 85, 113, 141, and 169
|
RI Period; Mean Change in DAS 28 (CRP) From RI Period Baseline (Day 169) Over Time
Time Frame: Days 169 (Period III Baseline), 197, 225, and 253
|
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.
|
Days 169 (Period III Baseline), 197, 225, and 253
|
LI; Number of Participants With Deaths, Serious Adverse Events (SAEs), SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
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
|
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.
|
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
|
LI Period; Number of Participants With AEs of Special Interest
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
|
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)
|
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
|
LI; Number of Participants With Hematology Values Meeting the Marked Abnormality (MA) Criteria
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
|
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.
|
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
|
LI; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria
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
|
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
|
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
|
LI; Number of Participants With Electrolyte Values Meeting the Marked Abnormality Criteria
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
|
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
|
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
|
LI; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria
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
|
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
|
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
|
LI Period; Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time Frame: Days 1, 15, 29, 57, 78, and 85
|
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.
|
Days 1, 15, 29, 57, 78, and 85
|
LI Period; Mean Heart Rate (HR)
Time Frame: Days 1, 15, 29, 57, 78, and 85
|
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.
|
Days 1, 15, 29, 57, 78, and 85
|
LI Period; Mean Temperature (T)
Time Frame: Days 1, 15, 29, 57, 78, and 85
|
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.
|
Days 1, 15, 29, 57, 78, and 85
|
DBW; Number of Participants With Death, Serious SAEs, Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation
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
|
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.
|
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
|
DBW; Number of Participants With AEs of Special Interest
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
|
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)
|
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
|
DBW; Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria
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
|
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.
|
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
|
DBW; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria
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
|
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
|
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
|
DBW; Number of Participants With Electrolytes Values Meeting the Marked Abnormality Criteria
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
|
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
|
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
|
DBW; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria
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
|
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
|
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
|
DBW; Mean Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During Double Blind Period
Time Frame: Days 113, 141, and 169
|
Blood pressures were taken in participants while seated, just prior to study drug injection, and measured in millimeters of mercury (mmHg).
|
Days 113, 141, and 169
|
DBW Period; Mean Heart Rate (HR) During Period 2
Time Frame: Days 113, 141, and 169
|
Heart Rate was taken in participants while seated, just prior to study drug injection, and measured in beats per minute (bpm)
|
Days 113, 141, and 169
|
DBW Period; Mean Temperature (T) During Period II
Time Frame: Days 113, 141, and 169
|
Participants were seated and temperature taken just prior to study drug injection.
|
Days 113, 141, and 169
|
RI; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation
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.
|
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.
|
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.
|
RI; Number of Participants With AEs of Special Interest
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.
|
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)
|
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.
|
RI; Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria
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.
|
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.
|
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.
|
RI; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria
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.
|
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
|
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.
|
RI; Number of Participants With Electrolytes Values Meeting the Marked Abnormality Criteria
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.
|
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
|
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.
|
RI; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria
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.
|
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
|
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.
|
RI Period; Mean Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During Period III
Time Frame: Days 169, 197, 225, and 253
|
Days 169, 197, 225, and 253
|
|
RI Period; Mean Heart Rate (HR) During Period III
Time Frame: Days 169, 197, 225, and 253
|
Days 169, 197, 225, and 253
|
|
RI Period; Mean Temperature (T) During Period III
Time Frame: Days 169, 197, 225, and 253
|
Days 169, 197, 225, and 253
|
|
Short Term; Abatacept Serum Concentration by Immunogenicity Status as Measured by ELISA by RI Treatment Groups
Time Frame: Day 197 through Day 253
|
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.
|
Day 197 through Day 253
|
Short Term; Abatacept Serum Concentration by Immunogenicity Status as Measured by ECL by RI Treatment Groups
Time Frame: Day 197 through Day 253
|
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.
|
Day 197 through Day 253
|
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
Time Frame: Baseline, Day 253
|
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.
|
Baseline, Day 253
|
LTE: DAS28-CRP Mean Change From Baseline (Day 1) Over Time - All Participants Treated in LTE
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.
|
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.
|
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.
|
LTE: Percent of Participants Who Achieved Clinical Remission in the Long Term Extension - All Participants Treated in LTE
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
|
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.
|
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
|
LTE: Percent of Participants With Low Disease Activity in Long Term Extension: All Participants Treated in LTE
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.
|
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.
|
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.
|
LTE: Percent of Participants With HAQ Response Over Time - All Participants Treated in LTE
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
|
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.
|
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
|
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
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
|
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.
|
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
|
LTE: Number of Participants With Death, Related SAEs, SAEs Leading to Discontinuation, Related AEs, or AEs Leading to Discontinuation During Long Term Extension (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.
|
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.
|
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.
|
LTE: Number of Participants With AEs of Special Interest During 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.
|
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)
|
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.
|
LTE: Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria During LTE
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.
|
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.
|
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.
|
LTE: Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria During LTE
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.
|
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
|
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.
|
LTE: Number of Participants With Electrolyte Values Meeting the Marked Abnormality Criteria During LTE
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.
|
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
|
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.
|
LTE: Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria During LTE
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.
|
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
|
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.
|
LTE: Mean Seated Systolic Blood Pressure (SBP) During LTE
Time Frame: Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261,1345, 1457,1541,1625,1709,1821,1905,1989,2073
|
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.
|
Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261,1345, 1457,1541,1625,1709,1821,1905,1989,2073
|
LTE: Mean Seated Diastolic Blood Pressure (DBP) During LTE
Time Frame: Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
|
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.
|
Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
|
LTE: Mean Heart Rate (HR) During LTE
Time Frame: Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
|
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.
|
Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
|
LTE: Mean Temperature (T) During LTE
Time Frame: Days 337, 365, 449,533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
|
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.
|
Days 337, 365, 449,533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2007
Primary Completion (Actual)
December 1, 2008
Study Completion (Actual)
February 1, 2014
Study Registration Dates
First Submitted
September 20, 2007
First Submitted That Met QC Criteria
September 21, 2007
First Posted (Estimate)
September 24, 2007
Study Record Updates
Last Update Posted (Estimate)
April 23, 2015
Last Update Submitted That Met QC Criteria
April 22, 2015
Last Verified
April 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis
- Arthritis, Rheumatoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Immune Checkpoint Inhibitors
- Abatacept
Other Study ID Numbers
- IM101-167
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Rheumatoid Arthritis
-
Janssen Research & Development, LLCWithdrawnActive Rheumatoid Arthritis; Rheumatoid Arthritis
-
Centocor, Inc.CompletedRheumatoid Arthritis, Juvenile
-
National Institute of Arthritis and Musculoskeletal...Children's Hospital Medical Center, CincinnatiCompleted
-
University of PittsburghNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)CompletedRheumatoid Arthritis | Juvenile Rheumatoid ArthritisUnited States
-
University of Missouri-ColumbiaCompletedJuvenile Rheumatoid ArthritisUnited States
-
AmgenTerminated
-
Children's Hospital Medical Center, CincinnatiNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)CompletedJuvenile Rheumatoid ArthritisUnited States
-
AmgenImmunex CorporationCompletedJuvenile Rheumatoid Arthritis
-
Universidad Autonoma de Nuevo LeonCompletedRheumatoId ArthritisMexico
-
Hamad Medical CorporationUnknownRHEUMATOID ARTHRITISQatar
Clinical Trials on Abatacept
-
Bristol-Myers SquibbCompletedUlcerative ColitisUnited States, Australia, India, Korea, Republic of, Poland, Canada, France, Brazil, Mexico, Puerto Rico, Belgium, Switzerland, Italy, Netherlands, Germany, Ireland, South Africa, United Kingdom, Czech Republic
-
University Medical Center GroningenBristol-Myers SquibbCompletedSjögren's SyndromeNetherlands
-
Melbourne HealthNational Health and Medical Research Council, Australia; Juvenile Diabetes...Active, not recruitingDiabetes Mellitus, Type 1 | Type 1 DiabetesAustralia
-
Bristol-Myers SquibbCompletedRheumatoid ArthritisUnited States
-
National Institute of Allergy and Infectious Diseases...Immune Tolerance Network (ITN)CompletedMultiple Sclerosis, Relapsing-RemittingUnited States, Canada
-
Rüdiger B. MüllerBristol-Myers SquibbCompletedRheumatoid ArthritisSwitzerland
-
Karolinska InstitutetKing's College Hospital NHS Trust; Institute of Rheumatology, PragueCompletedDermatomyositis | PolymyositisSweden, Czechia
-
Bristol-Myers SquibbCompleted
-
Bristol-Myers SquibbCompletedRheumatoid ArthritisUnited States
-
Assistance Publique - Hôpitaux de ParisMinistry of Health, FranceCompleted