Safety and Efficacy of Abatacept Versus Placebo in Participants With Psoriatic Arthritis
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Terminated
CT.gov ID
NCT00534313
Collaborator
(none)
191
44
4
42
4.3
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to determine an optimal abatacept dosing regimen for the treatment of active arthritis due to psoriatic arthritis in patients who have had a prior inadequate response to disease-modifying antirheumatic drugs, including methotrexate and tumor necrosis factor alpha-blockade compounds.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
191 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase IIB, Multi-Dose, Multi-center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept Versus Placebo in the Treatment of Psoriatic Arthritis
Study Start Date
:
Nov 1, 2007
Actual Primary Completion Date
:
Dec 1, 2008
Actual Study Completion Date
:
May 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Abatacept (30/10) Abatacept (30 mg/kg) was administered as intravenous (iv) infusion over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. The dose was calculated based on screening visit weight of participants for dosing on Days 1 and 15 followed by fixed dosing as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg) thereafter. |
Drug: Abatacept
Solution, intravenous, monthly, short-term = 24 weeks (6 months)
Other Names:
|
| Active Comparator: Abatacept (10/10) Abatacept (10 mg/kg) was administered as iv infusion over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141 in the double-blind period and continued for next 18 months in the open-label period till Day 729. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg). |
Drug: Abatacept
Solution, intravenous, monthly, short-term = 24 weeks (6 months)
Other Names:
|
| Active Comparator: Abatacept (3/3) Abatacept (3 mg/kg) was administered as iv infusion over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. The dose was calculated based on screening visit weight of participants. |
Drug: Abatacept
Solution, intravenous, monthly, short-term = 24 weeks (6 months)
Other Names:
|
| Placebo Comparator: Placebo Placebo solution (5% dextrose in water for injection, 0.9% sodium chloride injection) by iv infusion was administered on Days 1, 15, and 29 and every 28 days thereafter till Day 141. |
Drug: Placebo
Solution, intravenous, placebo (double dummy), monthly, short-term = 24 weeks (6 months)
|
Outcome Measures
Primary Outcome Measures
- Long-term Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Drug-related AEs, AEs Leading to Discontinuation, and AEs of Interest [From Day 169 to Day 729]
Presp=prespecified; acute= ≤1 hour after start of infusion; periinfusional= ≤24 hours after start of infusion. AE=any new unfavorable symptom or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=an unfavorable medical event that at any dose results in death, significant disability, drug dependency/abuse, hospitalization or prolonged hospitalization; is life-threatening, an important medical event, or a congenital anomaly/birth defect. Drug-related=possibly, probably, or certainly related and of unknown relationship to study drug.
- Short-term Period: Number of Participants With ACR 20 Response at Day 169 [At Day 169 from Baseline]
An ACR 20 responder was a participant who had a reduction of 20% or more from baseline in scores for both tender and swollen joints and had a reduction from baseline of 20% or more in 3 out of the following 5 assessments: participant's assessment of disease activity, participant's global assessment of disease activity, investigator's global assessment of disease activity, participant's assessment of physical function by HAQ-DI, and Disease Activity Score 28-C reactive protein.
Secondary Outcome Measures
- Long-term Period: Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR 50, ACR 70, ACR 90 Responses at Days 365 and 729 [At Days 365 and 729 from Baseline]
An ACR 20 (50, 70, 90) responder was a participant whose counts for both tender and swollen joints was reduced by 20% (50%, 70%, 90%, respectively) or more from baseline and who had a reduction of 20% (50%, 70%, 90%, respectively) or more from baseline in 3 of the following assessments: participant's assessment of disease activity, participant's global assessment of disease activity, Investigators Global Response, participant's assessment of physical function by Health Assessment Questionnaire Disability Index, and Disease Activity Score 28 based on C-reactive protein.
- Long-term Period: Number of Participants With an Investigators Global Assessment (IGA) Score of Clear or Almost Clear at Days 365 and 729 [From Day 169 to Days 365 and 729]
IGA score indicates lesion induration, scaling, and erythema: 0=clear (no signs of plaque psoriasis except for residual discoloration); 1=almost clear (just perceptible erythema, no induration to very slightly elevated above normal skin levels, limited amount of very fine scaling); 2=mild disease (mild erythema, mild induration, mainly fine scaling predominates); 3=moderate disease (moderate erythema [most plaques are red], moderate induration and/or coarse scale predominates); 4=severe (severe erythema, marked to very marked elevation of lesions, coarse thick scale predominates).
- Long-term Period: Mean Percentage of Change From Baseline in Target Lesion Score at Days 365 and 729 [From Baseline to Days 365 and 729]
Target lesion score is a measurement of the degree of erythema, induration, and scale of a psoriatic lesion, at least 2 cm in diameter, selected as a target for response throughout the study period. The scores assigned were 0=clear, 1=almost clear, 2=mild clear, 3=moderate disease, 4=severe. Percent improvement from baseline was computed using the ratio of improvement from baseline to the baseline value.
- Long-term Period: Mean Change From Baseline in the Short-form 36 (SF-36), Version 2, Domain and Component Scores at Days 365 and 729 [At Days 365 and 729 from baseline]
PCS=physical component score; MCS=mental component score. The SF-36 is a 36-item instrument with physical and mental components and covers quality of life (QoL) domains: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QoL. Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement.
- Long-term Period: Number of Participants Achieving A Reduction of At Least 0.3 Unit From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Days 365 and 729 [Days 365 and 729 from baseline]
Per the HAQ-DI, participants assessed their own ability to perform the following tasks: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity over a period by marking their responses on a questionnaire. Scoring of the HAQ-DI: 0=without any difficulty; 1=with some difficulty; 2=with much difficulty); and 3=unable to do. Greater score=greater disability. Responders with a >= 0.3 unit decrease in index scores from baseline to days 365 and 729 were considered to be improved.
- Short-term Period: Number of Participants With Marked Abnormalities in Hematology [From Baseline to Day 169]
LLN=lower limit of normal; ULN=upper limit of normal; pre-Rx=pretreatment. Marked abnormalities are laboratory measurements marked as abnormal, per predefined study criteria, at any study time point. Criteria: Hemoglobin >3 g/dL decrease from pre-Rx value; hematocrit <0.75*pre-Rx value; erythrocytes <0.75*pre-Rx value; platelets <0.67*LLN (or, if pre-Rx value <LLN, <0.5*pre-Rx value and <100000/mm^3) or >1.5*ULN.
- Short-term Period: Number of Participants With Marked Abnormalities in Hematology (Continued) [From Baseline to Day 169]
LLN=lower limit of normal; ULN=upper limit of normal; pre-Rx=pretreatment. Laboratory measurements are marked as abnormal per predefined study criteria, at any study time point. Criteria for the data presented. Leukocytes <0.75*LLN or >1.25*ULN (or, if pre-Rx value <LLN, <0.8*pre-Rx or >ULN. If pre-Rx value >ULN, >1.2*pre-Rx or <LLN); neutrophils+bands (absolute) <1.00*10^3 c/uL; lymphocytes (absolute) <0.75*10^3 c/uL or >7.50*10^3 c/uL; monocytes (absolute) >2000/mm^3; basophils (absolute) >0.40*10^3 c/uL; eosinophils (absolute) >0.75*10^3 c/uL.
- Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry [Baseline to Day 169]
ULN=upper limit of normal; pre-Rx=pretreatment. Marked abnormality criteria: Alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) >2*ULN (if pre-Rx >ULN, >3*pre-Rx); aspartate aminotransferase (AST), alanine transaminase (ALT) >3*ULN (if pre-Rx >ULN, >4*pre-Rx); bilirubin (total) >2*ULN (if pre-Rx >ULN, >4*pre-Rx); blood urea nitrogen (BUN) >2*pre-Rx; creatinine >1.5*pre-Rx.
- Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued) [Baseline to Day 169]
LLN=lower limit of normal; ULN=upper limit of normal; pre-Rx=pretreatment. Marked abnormality criteria: Sodium <0.95*LLN or >1.05*ULN (if pre-Rx<LLN, <0.95*pre-Rx or >ULN. If pre-Rx >ULN,>1.05* pre-Rx or <LLN); potassium, chloride <0.9*LLN or >1.1*ULN (if pre-Rx <LLN, <0.9*pre-Rx or >ULN. If pre-Rx >ULN, >1.1*pre-Rx or <LLN); calcium <0.8*LLN or >1.2*ULN (if pre-Rx <LLN,<0.75* pre-Rx or >ULN. If pre-Rx >ULN, >1.25* pre-Rx or <LLN); phosphorous <0.75*LLN or >1.25*ULN (if pre-Rx <LLN, <0.67*pre-Rx or >ULN. If pre-Rx >ULN, >1.33*pre-Rx or <LLN.
- Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued) [From Baseline to Day 169]
LLN=lower limit of normal; ULN=upper limit of normal; pre-Rx=pretreatment. Marked abnormality criteria: Glucose <65 or >220 mg/dL; glucose (fasting)<0.8*LLN or >1.5*ULN (if pre-Rx <LLN, <0.8*pre-Rx or >ULN. If pre-Rx >ULN, t>2.0*pre-Rx or <LLN). Protein (total) <0.9*LLN or >1.1*ULN (if pre-Rx <LLN, <0.9*pre-Rx or >ULN. If pre-Rx >ULN, >1.1*pre-Rx or <LLN). Albumin <0.9*LLN (if pre-Rx <LLN, <0.75* pre-Rx). Uric acid >1.5*ULN; if pre-Rx >ULN or >2*pre-Rx value.
- Short-term Period: Number of Participants With Marked Abnormalities in Urinalysis [From Baseline to Day 169]
Pre-Rx=pretreatment. Criteria for marked abnormality: Protein, glucose, blood, leukocyte esterase, red blood cells (RBC), white blood cells (WBC) >=2+ (or, if value >=4, or if pre-Rx value=0 or 0.5, >= 2* or if pre-RX value =1, >=3, or if pre-Rx =2 or 3, >=4).
- Short-term Period: Number of Participants Who Died and With SAEs, AEs, AEs Leading to Discontinuation, SAEs Leading to Discontinuation, Drug-related AEs, and Drug-related SAEs [From Baseline to Day 169]
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.
- Short-term Period: Number of Participants With an IGA Score of Clear or Almost Clear at Day 169 [At Day 169 from Baseline]
Score indicates lesion induration, scaling, and erythema: 0 = clear (no signs of plaque psoriasis except for residual discoloration); 1 = almost clear (just perceptible erythema, no induration to very slightly elevated above normal skin levels, limited amount of very fine scaling); 2 = mild disease (mild erythema, mild induration, mainly fine scaling predominates); 3 = moderate disease (moderate erythema [most plaques are red], moderate induration and/or coarse scale predominates); 4=severe (severe erythema, marked to very marked elevation of lesions, coarse thick scale predominates).
- Short-term Period: Mean Percentage of Change From Baseline in Target Lesion Score at Day 169 [At Day 169 from Baseline]
Target lesion score measures the degree of erythema, induration, and scale of a psoriatic lesion with a diameter of at least 2 cm, selected as a target for response throughout the study period. Scores: 0=clear, 1=almost clear, 2=mild clear, 3=moderate disease, 4=severe. Percent improvement from baseline was computed using the ratio of improvement from baseline to the baseline value.
- Short-term Period: Number of Participants With Positive Responses for Serum Levels of Abatacept-specific Antibodies (Anti-Abatacept-C) [From Baseline to Day 169]
Meso Scale Discovery electrochemiluminescence, a validated, sensitive immunoassay technique (anti-abatacept assay C) was used to measure serum levels of abatacept-specific antibodies against the whole molecule (both the CTLA4 and possibly immunoglobulin G portion [anti-abatacept antibody].
- Short-term Period: Mean Change From Baseline in the Mental Component Summary Score as Measured by the Short-form 36 at Day 169 [At Day 169 from Baseline]
PCS=physical component score; MCS=mental component score. The Short-form 36 is a 36-item instrument with physical and mental components and covers quality of life (QoL) domains: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QoL. Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement.
- Short-term Period: Mean Serum Concentrations of Abatacept [Days 1, 15, 29, 57, 85, 113, 141, and 169]
Abatacept was assayed using a validated enzyme linked immunosorbent assay method (ELISA). Serum concentration versus time data was analyzed in the descriptive pharmacokinetic (PK) analysis.
- Short-term Period: Mean Serum Trough Concentrations (Cmin) of Abatacept [Days 1, 15, 29, 57, 85, 113, 141, and 169]
Abatacept was assayed using a validated ELISA method. Cmin of abatacept was obtained from concentration versus time data.
- Short-term Period: Population Pharmacokinetic (POPPK) Analysis of the Pharmacokinetic (PK) Parameters [Days 1, 15, 29, 57, 85, 113, 141, and 169]
PK data: summaries of concentrations and concentration versus time plots were obtained. These data were to be used to develop a POPPK model using a nonlinear mixed-effects model. Prediction of PK data for each of the 3 abatacept treatment groups using POPPK methodology was not performed, because it would not provide any relevant information over the observed PK data.
- Short-term Period: Mean Change From Baseline in Physical Component Summary Score as Measured by the Short-form 36 at Day 169 [At Day 169 from Baseline]
PCS=physical component score; MCS=mental component score. The Short-form 36 is a 36-item instrument with physical and mental components and covers quality of life (QoL) domains: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QoL. Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement.
- Short-term Period: Number of Participants Achieving a Reduction of At Least 0.3 Unit From Baseline in HAQ-DI Scores at Day 169 [At Day 169 from Baseline]
The HAQ-DI assesses a participant's ability to perform the following tasks: dress/groom; arise; eat; walk; reach; grip; maintain hygiene; and maintain daily activity over a period by marking their response on a questionnaire. Responses/scores range from: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=to unable to do. Higher total score=greater disability.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
-
Meeting classification criteria for psoriatic arthritis for a duration of disease of at least 3 months
-
Prior failure (inefficacy or intolerance) of therapy with disease-modifying antirheumatic drugs; if patient had prior failure of methotrexate, he or she must have been taking at least 15 mg per week for at least 2 months
-
If recent failure(inefficacy or intolerance) of a tumor necrosis factor α-blockade compound, participant must be washed out prior to first dose: 56 days for infliximab and 28 days for etanercept and adalimumab
-
Disease activity as defined by a tender joint count of ≥3, swollen joint count of ≥3, and clinically detectable synovitis at screening and Day 01 (prior to infusion)
-
Active psoriasis with a qualifying target lesion ≥2 cm in diameter
-
Able to undergo magnetic resonance imaging
-
Use of appropriate birth control by women of child bearing potential (WOCBP)
Key Exclusion Criteria:
-
WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 10 weeks after the last dose of investigational product
-
Women who are pregnant or breastfeeding or who plan to become pregnant or to start breastfeeding during the duration of the study
-
Women with a positive pregnancy test on enrollment or prior to investigational product administration.
-
Participants scheduled for or anticipating joint replacement surgery.
-
Those with a recent history of clinically significant drug or alcohol abuse
-
Concomitant illness that in the investigator's opinion is likely to require systemic glucocorticosteroid therapy during the study (for example: moderate to severe asthma)
-
Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, pulmonary, cardiac, neurologic, ophthalmologic, or cerebral disease.
-
Unwillingness or inability to undergo screening based on current local or country guidelines/standards to evaluate the presence of cancer
-
Cancer within the last 5 years
-
Current malignancy or signs of possible malignancy detected by screening procedures for which the workup to exclude malignancy has not been completed or malignancy cannot be excluded
-
At risk for or history (within 3 years) of tuberculosis
-
Any serious bacterial infection within the last 3 months, not treated and resolved with antibiotics, or any chronic bacterial infection (such as, but not limited to, chronic pyelonephritis, osteomyelitis, and bronchiectasis)
-
Evidence of active or latent bacterial or viral infection infections at the time of potential enrollment
-
Herpes zoster or cytomegalovirus resolving less than 2 months prior to signing informed consent
-
Receipt of any live vaccines within 3 months of the anticipated first dose of study medication or anticipation of the need for a live vaccine at any time during and for 3 months after the duration of the study
Long-term period participants: Must have met eligibility criteria for short-term period and completed short-term (24-week) period of the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rheumatology Associates Of North Alabama | Huntsville | Alabama | United States | 35801 |
| 2 | Desert Medical Advances | Palm Desert | California | United States | 92260 |
| 3 | Stanford University School Of Medicine | Palo Alto | California | United States | 94304 |
| 4 | Boling Clinical Trials | Upland | California | United States | 91786 |
| 5 | Joao Nascimento | Bridgeport | Connecticut | United States | 06606 |
| 6 | New England Research Associates, Llc | Trumbull | Connecticut | United States | 06611 |
| 7 | Sarasota Arthritis Research Center | Sarasota | Florida | United States | 34239 |
| 8 | Clinical Pharmacology Study Group | Worcester | Massachusetts | United States | 01610 |
| 9 | Justus Fiechtner, Md, Mph | Lansing | Michigan | United States | 48910 |
| 10 | St. Paul Rheumatology P.A. | Eagan | Minnesota | United States | 55121 |
| 11 | Midwest Arthritis Center | Kalamazoo | Minnesota | United States | 49048 |
| 12 | Arthritis Clinic & Carolina Bone & Joint, Pa | Charlotte | North Carolina | United States | 28210 |
| 13 | Deaconess Hospital | Cincinnati | Ohio | United States | 45219 |
| 14 | Health Research Of Oklahoma | Oklahoma City | Oklahoma | United States | 73103 |
| 15 | Altoona Center For Clinical Research | Duncansville | Pennsylvania | United States | 16635 |
| 16 | Rheumatic Disease Associates, Ltd. | Willow Grove | Pennsylvania | United States | 19090 |
| 17 | Chase, Walter F. | Austin | Texas | United States | 78705 |
| 18 | Seattle Rheumatology Associates | Seattle | Washington | United States | 98104 |
| 19 | Arthritis Northwest | Spokane | Washington | United States | 99204 |
| 20 | Local Institution | Capital Federal | Buenos Aires | Argentina | 1015 |
| 21 | Local Institution | Rosario | Santa Fe | Argentina | 2000 |
| 22 | Local Institution | Santa Fe | Argentina | 3000 | |
| 23 | Local Institution | Cairns | Queensland | Australia | 4872 |
| 24 | Local Institution | Maroochydore | Queensland | Australia | 4558 |
| 25 | Local Institution | Fitzroy, Melbourne | Victoria | Australia | 3065 |
| 26 | Local Institution | Hasselt | Belgium | 3500 | |
| 27 | Local Institution | Leuven | Belgium | 3000 | |
| 28 | Local Institution | St. John'S | Newfoundland and Labrador | Canada | A1B 3E1 |
| 29 | Local Institution | Montreal | Quebec | Canada | H2L 1S6 |
| 30 | Local Institution | Trois-Rivieres | Quebec | Canada | G8Z 1Y2 |
| 31 | Local Institution | Quebec | Canada | G1W 4R4 | |
| 32 | Local Institution | Chambray Les Tours | France | 37170 | |
| 33 | Local Institution | Lille | France | 59037 | |
| 34 | Local Institution | Montpellier Cedex 5 | France | 34295 | |
| 35 | Local Institution | Frankfurt/Main | Germany | 60590 | |
| 36 | Local Institution | Hamburg | Germany | 22081 | |
| 37 | Local Institution | Hildesheim | Germany | 31134 | |
| 38 | Local Institution | Napoli | Italy | 80131 | |
| 39 | Local Institution | Potenza | Italy | 85100 | |
| 40 | Local Institution | Reggio Emilia | Italy | 42100 | |
| 41 | Local Institution | Amsterdam | Netherlands | 1105 AZ | |
| 42 | Local Institution | Lillehammer | Norway | 2609 | |
| 43 | Local Institution | Panorama | Western Cape | South Africa | 7500 |
| 44 | Local Institution | A Coruna | Spain | 15006 |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00534313
Other Study ID Numbers:
- IM101-158
- EUDRACT 2007-004241-15
First Posted:
Sep 24, 2007
Last Update Posted:
Aug 1, 2012
Last Verified:
Jul 1, 2012
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 191 participants were enrolled and 21 were not randomized. Reasons for this included: adverse events (AEs) (2); participant withdrew consent (5); lost to follow up (1); participant no longer meets study criteria (13). |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered intravenous (iv) infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Day 1 and 15 followed by fixed dose based on their screening visit weight i.e. for participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg and participants weighing > 100 kg received 1000 mg. | Participants were administered iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg and participants weighing > 100 kg received 1000mg). | Participants were administered iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants were administered iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 141. |
| Period Title: Short-term Period | ||||
| STARTED | 43 | 40 | 45 | 42 |
| COMPLETED | 37 | 34 | 43 | 33 |
| NOT COMPLETED | 6 | 6 | 2 | 9 |
| Period Title: Short-term Period | ||||
| STARTED | 37 | 34 | 43 | 33 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 37 | 34 | 43 | 33 |
Baseline Characteristics
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered intravenous (iv) infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Day 1 and 15 followed by fixed dose based on their screening visit weight i.e. for participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg and participants weighing > 100 kg received 1000 mg. | Participants were administered iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg and participants weighing > 100 kg received 1000mg). | Participants were administered iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants were administered iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 141. | Total of all reporting groups |
| Overall Participants | 43 | 40 | 45 | 42 | 170 |
| Age (years) [Median (Full Range) ] | |||||
| Median (Full Range) [years] |
54.0
|
51.5
|
51.0
|
53.0
|
52.0
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
23
53.5%
|
14
35%
|
23
51.1%
|
19
45.2%
|
79
46.5%
|
| Male |
20
46.5%
|
26
65%
|
22
48.9%
|
23
54.8%
|
91
53.5%
|
| Race/Ethnicity, Customized (participants) [Number] | |||||
| White |
43
100%
|
38
95%
|
44
97.8%
|
41
97.6%
|
166
97.6%
|
| Asian |
0
0%
|
2
5%
|
1
2.2%
|
0
0%
|
3
1.8%
|
| Pacific |
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
1
0.6%
|
| Weight (kilograms) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [kilograms] |
92.9
(21.3)
|
85.0
(17.9)
|
85.0
(19.1)
|
96.0
(19.4)
|
89.7
(19.9)
|
Outcome Measures
| Title | Long-term Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Drug-related AEs, AEs Leading to Discontinuation, and AEs of Interest |
|---|---|
| Description | Presp=prespecified; acute= ≤1 hour after start of infusion; periinfusional= ≤24 hours after start of infusion. AE=any new unfavorable symptom or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=an unfavorable medical event that at any dose results in death, significant disability, drug dependency/abuse, hospitalization or prolonged hospitalization; is life-threatening, an important medical event, or a congenital anomaly/birth defect. Drug-related=possibly, probably, or certainly related and of unknown relationship to study drug. |
| Time Frame | From Day 169 to Day 729 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of abatacept during the long-term period. |
| Arm/Group Title | All Treated Participants |
|---|---|
| Arm/Group Description | Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. |
| Measure Participants | 147 |
| Deaths |
0
0%
|
| SAEs |
20
46.5%
|
| Drug-related SAEs |
4
9.3%
|
| SAEs leading to discontinuation |
0
0%
|
| AEs |
123
286%
|
| Drug-related AEs |
58
134.9%
|
| AES leading to discontinuation |
4
9.3%
|
| AEs of Interest (AEI): Infections |
83
193%
|
| AEI: Malignancy |
2
4.7%
|
| AEI: Autoimmune disorders (presp) |
5
11.6%
|
| AEI: Infusion reactions (presp): Acute |
4
9.3%
|
| AEI: Infusion reactions (presp): Periinfusional |
11
25.6%
|
| Title | Long-term Period: Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR 50, ACR 70, ACR 90 Responses at Days 365 and 729 |
|---|---|
| Description | An ACR 20 (50, 70, 90) responder was a participant whose counts for both tender and swollen joints was reduced by 20% (50%, 70%, 90%, respectively) or more from baseline and who had a reduction of 20% (50%, 70%, 90%, respectively) or more from baseline in 3 of the following assessments: participant's assessment of disease activity, participant's global assessment of disease activity, Investigators Global Response, participant's assessment of physical function by Health Assessment Questionnaire Disability Index, and Disease Activity Score 28 based on C-reactive protein. |
| Time Frame | At Days 365 and 729 from Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of abatacept in the long-term (open-label) period. (n=number of participants with a response) |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Short-term period: Participants received IV infusions of abatacept (30 mg/kg, calculated-dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed-dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg. Long-term period: Participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg). Long-term period: Participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of abatacept (3 mg/kg, calculated-dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. Long-term period: Participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. Long-term period: Participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. |
| Measure Participants | 37 | 34 | 43 | 33 |
| ACR 20, Day 365 (n=34, 29, 36, 32) |
50.0
116.3%
|
62.1
155.3%
|
61.1
135.8%
|
46.9
111.7%
|
| ACR 20, Day 729 (n=21, 18, 26, 18) |
81
188.4%
|
66.7
166.8%
|
65.4
145.3%
|
72.2
171.9%
|
| ACR 50, Day 365 (n=34, 29, 36, 32) |
23.5
54.7%
|
37.9
94.8%
|
33.3
74%
|
34.4
81.9%
|
| ACR 50, Day 729 (n=21, 18, 26, 18) |
57.1
132.8%
|
27.8
69.5%
|
42.3
94%
|
55.6
132.4%
|
| ACR 70, Day 365 (n=34, 29, 36, 32) |
5.9
13.7%
|
17.2
43%
|
13.9
30.9%
|
18.8
44.8%
|
| ACR 70, Day 729 (n=21, 18, 26, 18) |
23.8
55.3%
|
16.7
41.8%
|
23.1
51.3%
|
11.1
26.4%
|
| ACR 90, Day 365 (n=34, 29, 36, 32) |
0
0%
|
6.9
17.3%
|
5.6
12.4%
|
6.3
15%
|
| ACR 90, Day 729 (n=21, 18, 26, 18) |
0
0%
|
5.6
14%
|
11.5
25.6%
|
0
0%
|
| Title | Long-term Period: Number of Participants With an Investigators Global Assessment (IGA) Score of Clear or Almost Clear at Days 365 and 729 |
|---|---|
| Description | IGA score indicates lesion induration, scaling, and erythema: 0=clear (no signs of plaque psoriasis except for residual discoloration); 1=almost clear (just perceptible erythema, no induration to very slightly elevated above normal skin levels, limited amount of very fine scaling); 2=mild disease (mild erythema, mild induration, mainly fine scaling predominates); 3=moderate disease (moderate erythema [most plaques are red], moderate induration and/or coarse scale predominates); 4=severe (severe erythema, marked to very marked elevation of lesions, coarse thick scale predominates). |
| Time Frame | From Day 169 to Days 365 and 729 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of abatacept in the long-term (open-label) period. (n=number of participants with a response) |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Short-term period: Participants received IV infusions of abatacept (30 mg/kg, calculated-dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed-dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg. Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg).Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of abatacept (3 mg/kg, calculated-dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight.Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. |
| Measure Participants | 37 | 34 | 43 | 33 |
| Day 365 (n=30, 29, 34, 23) |
13
30.2%
|
10
25%
|
19
42.2%
|
10
23.8%
|
| Day 729 (n=20, 17, 26, 18) |
10
23.3%
|
7
17.5%
|
16
35.6%
|
8
19%
|
| Title | Long-term Period: Mean Percentage of Change From Baseline in Target Lesion Score at Days 365 and 729 |
|---|---|
| Description | Target lesion score is a measurement of the degree of erythema, induration, and scale of a psoriatic lesion, at least 2 cm in diameter, selected as a target for response throughout the study period. The scores assigned were 0=clear, 1=almost clear, 2=mild clear, 3=moderate disease, 4=severe. Percent improvement from baseline was computed using the ratio of improvement from baseline to the baseline value. |
| Time Frame | From Baseline to Days 365 and 729 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of abatacept in the long-term (open-label) period. |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Short-term period: Participants received IV infusions of abatacept (30 mg/kg, calculated-dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed-dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg. Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg).Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of abatacept (3 mg/kg, calculated-dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. |
| Measure Participants | 37 | 34 | 43 | 33 |
| Day 365 |
27.51
(7.92)
|
41.97
(7.90)
|
20.32
(8.59)
|
33.82
(7.52)
|
| Day 729 |
49.14
(9.13)
|
45.07
(7.98)
|
44.79
(9.09)
|
34.41
(8.98)
|
| Title | Long-term Period: Mean Change From Baseline in the Short-form 36 (SF-36), Version 2, Domain and Component Scores at Days 365 and 729 |
|---|---|
| Description | PCS=physical component score; MCS=mental component score. The SF-36 is a 36-item instrument with physical and mental components and covers quality of life (QoL) domains: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QoL. Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement. |
| Time Frame | At Days 365 and 729 from baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Short-term period: Participants received intravenous (IV) infusions of abatacept (30 mg/kg, calculated-dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed-dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg. Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg).Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of abatacept (3 mg/kg, calculated-dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight.Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. |
| Measure Participants | 37 | 34 | 43 | 33 |
| Day 365 PCS (n=34, 32, 37,29) |
1.73
(1.10)
|
7.59
(1.36)
|
4.86
(1.67)
|
3.59
(1.19)
|
| Day 365 MCS (n=34,32, 37,29) |
2.73
(1.60)
|
1.07
(2.00)
|
4.95
(2.10)
|
4.40
(2.00)
|
| Day 729 PCS (n=20,18, 26,18) |
5.59
(1.43)
|
7.97
(2.0)
|
6.74
(1.95)
|
4.45
(1.14)
|
| Day 729 MCS (n=20,18, 26,18) |
5.89
(1.84)
|
-0.17
(2.71)
|
1.85
(2.11)
|
4.35
(2.29)
|
| Title | Long-term Period: Number of Participants Achieving A Reduction of At Least 0.3 Unit From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Days 365 and 729 |
|---|---|
| Description | Per the HAQ-DI, participants assessed their own ability to perform the following tasks: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity over a period by marking their responses on a questionnaire. Scoring of the HAQ-DI: 0=without any difficulty; 1=with some difficulty; 2=with much difficulty); and 3=unable to do. Greater score=greater disability. Responders with a >= 0.3 unit decrease in index scores from baseline to days 365 and 729 were considered to be improved. |
| Time Frame | Days 365 and 729 from baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of abatacept in the long-term (open-label) period. (n=number of participants with responses available) |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Short-term period: Participants received intravenous (IV) infusions of abatacept (30 mg/kg, calculated-dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed-dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg. Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg).Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of abatacept (3 mg/kg, calculated-dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight.Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Short-term period: Participants received IV infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. |
| Measure Participants | 37 | 34 | 43 | 33 |
| Day 365 (n=3, 28, 32, 23) |
12
27.9%
|
16
40%
|
17
37.8%
|
12
28.6%
|
| Day 729 (n=9, 11, 13, 10) |
9
20.9%
|
11
27.5%
|
13
28.9%
|
10
23.8%
|
| Title | Short-term Period: Number of Participants With Marked Abnormalities in Hematology |
|---|---|
| Description | LLN=lower limit of normal; ULN=upper limit of normal; pre-Rx=pretreatment. Marked abnormalities are laboratory measurements marked as abnormal, per predefined study criteria, at any study time point. Criteria: Hemoglobin >3 g/dL decrease from pre-Rx value; hematocrit <0.75*pre-Rx value; erythrocytes <0.75*pre-Rx value; platelets <0.67*LLN (or, if pre-Rx value <LLN, <0.5*pre-Rx value and <100000/mm^3) or >1.5*ULN. |
| Time Frame | From Baseline to Day 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of study medication during double-blind period. n=number of participants with evaluable results (each arm respectively). |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Day 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15,and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg and participants weighing >100 kg received 1000 mg). | Participants were administered iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants received iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 43 | 40 | 45 | 42 |
| Hemoglobin (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Hematocrit (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Erythrocytes (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Platelet count (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Short-term Period: Number of Participants With ACR 20 Response at Day 169 |
|---|---|
| Description | An ACR 20 responder was a participant who had a reduction of 20% or more from baseline in scores for both tender and swollen joints and had a reduction from baseline of 20% or more in 3 out of the following 5 assessments: participant's assessment of disease activity, participant's global assessment of disease activity, investigator's global assessment of disease activity, participant's assessment of physical function by HAQ-DI, and Disease Activity Score 28-C reactive protein. |
| Time Frame | At Day 169 from Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 infusion of study medication in the double-blind (short-term) period. Missing response values were imputed as nonresponders for participants who discontinued early after receiving study medication. |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Short-term period: Participants received intravenous (IV) infusions of abatacept (30 mg/kg, calculated-dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed-dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg. | Short-term period: Participants received IV infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg). | Short-term period: Participants received IV infusions of abatacept (3 mg/kg, calculated-dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Short-term period: Participants received IV infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 43 | 40 | 45 | 42 |
| Number [Participants] |
18
41.9%
|
19
47.5%
|
15
33.3%
|
8
19%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | All Treated Participants, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.022 |
| Comments | The p-value (two-sided) was based on Cochran-Mantel-Haenszel method (CMH) with stratification of baseline body surface area (BSA) affected by psoriasis. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 22.9 | |
| Confidence Interval |
(2-Sided) 95% 4.0 to 41.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference was based on CMH with stratification of baseline BSA affected by psoriasis. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Abatacept 10/10, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.006 |
| Comments | p-value (two-sided) was based on CMH with stratification of baseline BSA affected by psoriasis. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 28.7 | |
| Confidence Interval |
(2-Sided) 95% 9.4 to 48.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference was based on CMH with stratification of baseline BSA affected by psoriasis. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Abatacept 3/3, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.121 |
| Comments | p-value (2-sided) was based on CMH with stratification of baseline BSA affected by psoriasis. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 14.6 | |
| Confidence Interval |
(2-Sided) 95% -3.5 to 32.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference was based on CMH with stratification of baseline BSA affected by psoriasis. | |
| Title | Short-term Period: Number of Participants With Marked Abnormalities in Hematology (Continued) |
|---|---|
| Description | LLN=lower limit of normal; ULN=upper limit of normal; pre-Rx=pretreatment. Laboratory measurements are marked as abnormal per predefined study criteria, at any study time point. Criteria for the data presented. Leukocytes <0.75*LLN or >1.25*ULN (or, if pre-Rx value <LLN, <0.8*pre-Rx or >ULN. If pre-Rx value >ULN, >1.2*pre-Rx or <LLN); neutrophils+bands (absolute) <1.00*10^3 c/uL; lymphocytes (absolute) <0.75*10^3 c/uL or >7.50*10^3 c/uL; monocytes (absolute) >2000/mm^3; basophils (absolute) >0.40*10^3 c/uL; eosinophils (absolute) >0.75*10^3 c/uL. |
| Time Frame | From Baseline to Day 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of study medication during double-blind period. n=number of participants with evaluable results (each arm respectively). |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants who received iv infusions of abatacept (30 mg/kg-calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Day 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg). | Participants received iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants received iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 43 | 40 | 45 | 42 |
| Leukocytes (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
2
4.4%
|
0
0%
|
| Neutrophils+bands (absolute) (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Lymphocytes (absolute) (n = 43, 40, 45, 41) |
2
4.7%
|
0
0%
|
6
13.3%
|
1
2.4%
|
| Monocytes (absolute) (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Basophils (absolute) (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Eosinophils (absolute) (n = 43, 40, 45, 41) |
1
2.3%
|
1
2.5%
|
1
2.2%
|
0
0%
|
| Title | Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry |
|---|---|
| Description | ULN=upper limit of normal; pre-Rx=pretreatment. Marked abnormality criteria: Alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) >2*ULN (if pre-Rx >ULN, >3*pre-Rx); aspartate aminotransferase (AST), alanine transaminase (ALT) >3*ULN (if pre-Rx >ULN, >4*pre-Rx); bilirubin (total) >2*ULN (if pre-Rx >ULN, >4*pre-Rx); blood urea nitrogen (BUN) >2*pre-Rx; creatinine >1.5*pre-Rx. |
| Time Frame | Baseline to Day 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of study medication during the double-blind period. n=number of participants with evaluable results (each arm respectively). |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg). | Participants received iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15,and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants received iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 43 | 40 | 45 | 42 |
| ALP (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AST (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ALT (n = 43, 40, 45, 41) |
1
2.3%
|
0
0%
|
0
0%
|
0
0%
|
| GGT (n = 43, 40, 45, 41) |
1
2.3%
|
0
0%
|
0
0%
|
0
0%
|
| Bilirubin (total) (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| BUN (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Creatinine (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued) |
|---|---|
| Description | LLN=lower limit of normal; ULN=upper limit of normal; pre-Rx=pretreatment. Marked abnormality criteria: Sodium <0.95*LLN or >1.05*ULN (if pre-Rx<LLN, <0.95*pre-Rx or >ULN. If pre-Rx >ULN,>1.05* pre-Rx or <LLN); potassium, chloride <0.9*LLN or >1.1*ULN (if pre-Rx <LLN, <0.9*pre-Rx or >ULN. If pre-Rx >ULN, >1.1*pre-Rx or <LLN); calcium <0.8*LLN or >1.2*ULN (if pre-Rx <LLN,<0.75* pre-Rx or >ULN. If pre-Rx >ULN, >1.25* pre-Rx or <LLN); phosphorous <0.75*LLN or >1.25*ULN (if pre-Rx <LLN, <0.67*pre-Rx or >ULN. If pre-Rx >ULN, >1.33*pre-Rx or <LLN. |
| Time Frame | Baseline to Day 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of study medication during the double-blind period. n=number of participants with evaluable results (each arm respectively). |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15,and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg). | Participants received iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants received iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 43 | 40 | 45 | 42 |
| Sodium (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Potassium (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
| Chloride (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Calcium (total) (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Phosphorous , inorganic (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
1
2.2%
|
1
2.4%
|
| Title | Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued) |
|---|---|
| Description | LLN=lower limit of normal; ULN=upper limit of normal; pre-Rx=pretreatment. Marked abnormality criteria: Glucose <65 or >220 mg/dL; glucose (fasting)<0.8*LLN or >1.5*ULN (if pre-Rx <LLN, <0.8*pre-Rx or >ULN. If pre-Rx >ULN, t>2.0*pre-Rx or <LLN). Protein (total) <0.9*LLN or >1.1*ULN (if pre-Rx <LLN, <0.9*pre-Rx or >ULN. If pre-Rx >ULN, >1.1*pre-Rx or <LLN). Albumin <0.9*LLN (if pre-Rx <LLN, <0.75* pre-Rx). Uric acid >1.5*ULN; if pre-Rx >ULN or >2*pre-Rx value. |
| Time Frame | From Baseline to Day 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of study medication during the double-blind period. n=number of participants with evaluable results. |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg). | Participants were administered iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants received iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 43 | 40 | 45 | 42 |
| Glucose (n = 43, 40, 45, 41) |
1
2.3%
|
4
10%
|
8
17.8%
|
2
4.8%
|
| Glucose, fasting (n = 16, 12, 12, 15) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Protein (total) (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Albumin (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Uric acid (n = 43, 40, 45, 41) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Short-term Period: Number of Participants With Marked Abnormalities in Urinalysis |
|---|---|
| Description | Pre-Rx=pretreatment. Criteria for marked abnormality: Protein, glucose, blood, leukocyte esterase, red blood cells (RBC), white blood cells (WBC) >=2+ (or, if value >=4, or if pre-Rx value=0 or 0.5, >= 2* or if pre-RX value =1, >=3, or if pre-Rx =2 or 3, >=4). |
| Time Frame | From Baseline to Day 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of study medication during the double-blind period. n = number of participants with evaluable results (each arm respectively). |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Day 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg). | Participants received iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants received iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15,and 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 43 | 40 | 45 | 42 |
| Protein (n = 42, 37, 38, 40) |
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
| Glucose (n = 42, 37, 38, 40) |
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
| Blood (n = 42, 37, 38, 40) |
2
4.7%
|
2
5%
|
3
6.7%
|
2
4.8%
|
| Leukocyte esterase (n = 3, 7, 4, 5) |
0
0%
|
0
0%
|
1
2.2%
|
1
2.4%
|
| WBC (n = 6, 8, 8, 6) |
1
2.3%
|
1
2.5%
|
3
6.7%
|
3
7.1%
|
| RBC (n = 6, 7, 5, 6) |
3
7%
|
1
2.5%
|
1
2.2%
|
2
4.8%
|
| Title | Short-term Period: Number of Participants Who Died and With SAEs, AEs, AEs Leading to Discontinuation, SAEs Leading to Discontinuation, Drug-related AEs, and Drug-related SAEs |
|---|---|
| Description | An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related to and of unknown relationship to study treatment. |
| Time Frame | From Baseline to Day 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of study medication during the double-blind period. |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg). | Participants were administered iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants received iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15,and 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 43 | 40 | 45 | 42 |
| Deaths |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| SAEs |
4
9.3%
|
2
5%
|
0
0%
|
1
2.4%
|
| AEs |
29
67.4%
|
31
77.5%
|
31
68.9%
|
30
71.4%
|
| All AEs Leading to Discontinuation |
1
2.3%
|
2
5%
|
1
2.2%
|
3
7.1%
|
| All SAEs Leading to Discontinuation |
1
2.3%
|
0
0%
|
0
0%
|
0
0%
|
| Drug-related AEs |
13
30.2%
|
13
32.5%
|
12
26.7%
|
7
16.7%
|
| Drug-related SAEs |
1
2.3%
|
1
2.5%
|
0
0%
|
0
0%
|
| Title | Short-term Period: Number of Participants With an IGA Score of Clear or Almost Clear at Day 169 |
|---|---|
| Description | Score indicates lesion induration, scaling, and erythema: 0 = clear (no signs of plaque psoriasis except for residual discoloration); 1 = almost clear (just perceptible erythema, no induration to very slightly elevated above normal skin levels, limited amount of very fine scaling); 2 = mild disease (mild erythema, mild induration, mainly fine scaling predominates); 3 = moderate disease (moderate erythema [most plaques are red], moderate induration and/or coarse scale predominates); 4=severe (severe erythema, marked to very marked elevation of lesions, coarse thick scale predominates). |
| Time Frame | At Day 169 from Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 infusion of study medication in double-blind (short-term) period. Missing response values were imputed as nonresponders for participants who discontinued early after receiving study medication. |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Short-term period: Participants received IV infusions of abatacept (30 mg/kg, calculated-dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed-dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg. | Short-term period: Participants received IV infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg). | Short-term period: Participants received IV infusions of abatacept (3 mg/kg, calculated-dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Short-term period: Participants received IV infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. Long-term period: participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. |
| Measure Participants | 43 | 40 | 45 | 42 |
| Number [Participants] |
9
20.9%
|
10
25%
|
17
37.8%
|
11
26.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | All Treated Participants, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -6.0 | |
| Confidence Interval |
(2-Sided) 95% -23.0 to 11.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference and 95% confidence intervals (CI) was based on CMH with stratification of baseline BSA affected by psoriasis. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Abatacept 10/10, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -18.0 to 17.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference and 95% CI was based on CMH with stratification of baseline BSA affected by psoriasis. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Abatacept 3/3, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 10.4 | |
| Confidence Interval |
(2-Sided) 95% -7.6 to 28.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference and 95% CI was based on CMH with stratification of baseline BSA affected by psoriasis. | |
| Title | Short-term Period: Mean Percentage of Change From Baseline in Target Lesion Score at Day 169 |
|---|---|
| Description | Target lesion score measures the degree of erythema, induration, and scale of a psoriatic lesion with a diameter of at least 2 cm, selected as a target for response throughout the study period. Scores: 0=clear, 1=almost clear, 2=mild clear, 3=moderate disease, 4=severe. Percent improvement from baseline was computed using the ratio of improvement from baseline to the baseline value. |
| Time Frame | At Day 169 from Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 infusion of study drug in double-blind (short-term) period. Only participants with both baseline and postbaseline values included. Missing values at Day 169 were imputed using the last observation carried forward values, except for participants with only baseline value. |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg). | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg). | Participants received iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose based on their screening visit weight. | Participants received iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15,and 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 43 | 40 | 45 | 42 |
| Mean (Standard Error) [Percentage of change] |
19.39
(9.16)
|
22.96
(9.46)
|
31.11
(8.98)
|
0.63
(9.35)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | All Treated Participants, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 18.77 | |
| Confidence Interval |
(2-Sided) 95% -7.02 to 44.56 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Abatacept 10/10, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 22.34 | |
| Confidence Interval |
(2-Sided) 95% -3.93 to 48.60 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Abatacept 3/3, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 30.48 | |
| Confidence Interval |
(2-Sided) 95% 4.82 to 56.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Short-term Period: Number of Participants With Positive Responses for Serum Levels of Abatacept-specific Antibodies (Anti-Abatacept-C) |
|---|---|
| Description | Meso Scale Discovery electrochemiluminescence, a validated, sensitive immunoassay technique (anti-abatacept assay C) was used to measure serum levels of abatacept-specific antibodies against the whole molecule (both the CTLA4 and possibly immunoglobulin G portion [anti-abatacept antibody]. |
| Time Frame | From Baseline to Day 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received abatacept and for whom baseline and at least 1 additional measurement were available during the double-blind (short-term) period. |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 |
|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Day 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 169. All participants received a dose based on their screening visit weight as per by rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000mg). | Participants received iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. |
| Measure Participants | 43 | 40 | 45 |
| Number [Participants] |
1
2.3%
|
0
0%
|
2
4.4%
|
| Title | Short-term Period: Mean Change From Baseline in the Mental Component Summary Score as Measured by the Short-form 36 at Day 169 |
|---|---|
| Description | PCS=physical component score; MCS=mental component score. The Short-form 36 is a 36-item instrument with physical and mental components and covers quality of life (QoL) domains: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QoL. Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement. |
| Time Frame | At Day 169 from Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized and treated participants with baseline and postbaseline measurements at Day 169. Missing values were imputed by Last Observation Carried Forward, except for participants with only baseline observations. |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg and participants weighing > 100 kg received 1000mg). | Participants were administered iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants received iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15,and 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 42 | 40 | 43 | 41 |
| Mean (Standard Error) [Units on a scale] |
4.50
(2.45)
|
4.42
(2.50)
|
3.16
(2.41)
|
2.41
(2.47)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | All Treated Participants, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 2.08 | |
| Confidence Interval |
() 95% -4.79 to 8.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Abatacept 10/10, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 2.01 | |
| Confidence Interval |
(2-Sided) 95% -4.94 to 8.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Abatacept 3/3, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.75 | |
| Confidence Interval |
(2-Sided) 95% -6.08 to 7.58 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Short-term Period: Mean Serum Concentrations of Abatacept |
|---|---|
| Description | Abatacept was assayed using a validated enzyme linked immunosorbent assay method (ELISA). Serum concentration versus time data was analyzed in the descriptive pharmacokinetic (PK) analysis. |
| Time Frame | Days 1, 15, 29, 57, 85, 113, 141, and 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of study medication and were evaluable for PK analysis during double-blind period. n= number of participants with evaluable PK results in each arm respectively. |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 |
|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg). | Participants received iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. |
| Measure Participants | 43 | 40 | 45 |
| Day 1 (n= 13, 13, 44) |
0
(0)
|
0.01
(0.01)
|
0
(0)
|
| Day 15 (n= 43, 38, 42) |
119.99
(35.30)
|
48.29
(17.96)
|
14.28
(7.67)
|
| Day 29 (n= 41, 39, 43) |
186.82
(62.49)
|
49.70
(16.79)
|
16.20
(4.86)
|
| Day 57 (n= 40, 39, 44) |
58.55
(26.09)
|
25.75
(9.67)
|
10.42
(5.75)
|
| Day 85 (n= 37, 35, 41) |
39.00
(19.37)
|
26.29
(10.59)
|
8.73
(3.26)
|
| Day 113 ( n= 35, 33, 43) |
36.30
(19.94)
|
32.69
(14.08)
|
8.85
(5.01)
|
| Day 141 (n= 35, 34, 42) |
26.70
(9.24)
|
25.78
(9.74)
|
7.66
(3.13)
|
| Day 169 (n= 36, 42, 34) |
28.93
(11.29)
|
26.34
(10.75)
|
9.29
(5.23)
|
| Title | Short-term Period: Mean Serum Trough Concentrations (Cmin) of Abatacept |
|---|---|
| Description | Abatacept was assayed using a validated ELISA method. Cmin of abatacept was obtained from concentration versus time data. |
| Time Frame | Days 1, 15, 29, 57, 85, 113, 141, and 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 infusion of study medication and were evaluable for PK analysis during double-blind period. n= number of participants with evaluable PK results in each arm respectively. |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 |
|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000mg). | Participants received iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. |
| Measure Participants | 43 | 40 | 45 |
| Day 15 (n= 43, 38, 43) |
115.35
|
45.10
|
12.81
|
| Day 29 (n= 41, 39, 43) |
176.22
|
46.86
|
15.43
|
| Day 57 (n= 40, 39, 44) |
53.08
|
23.88
|
9.03
|
| Day 85 (n= 37, 35, 41) |
33.09
|
24.36
|
8.15
|
| Day 113 (n= 35, 33, 43) |
31.50
|
29.60
|
7.56
|
| Day 141 (n= 35, 34, 42) |
25.02
|
23.62
|
6.91
|
| Day 169 (n= 36, 34, 42) |
26.65
|
24.33
|
7.84
|
| Title | Short-term Period: Population Pharmacokinetic (POPPK) Analysis of the Pharmacokinetic (PK) Parameters |
|---|---|
| Description | PK data: summaries of concentrations and concentration versus time plots were obtained. These data were to be used to develop a POPPK model using a nonlinear mixed-effects model. Prediction of PK data for each of the 3 abatacept treatment groups using POPPK methodology was not performed, because it would not provide any relevant information over the observed PK data. |
| Time Frame | Days 1, 15, 29, 57, 85, 113, 141, and 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg). | Participants received iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants were administered iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Short-term Period: Mean Change From Baseline in Physical Component Summary Score as Measured by the Short-form 36 at Day 169 |
|---|---|
| Description | PCS=physical component score; MCS=mental component score. The Short-form 36 is a 36-item instrument with physical and mental components and covers quality of life (QoL) domains: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QoL. Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement. |
| Time Frame | At Day 169 from Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received treatment and with baseline and postbaseline measurements at Day 169. Missing values were imputed by Last Observation Carried Forward, except for participants with only baseline observations. |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg -calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg). | Participants received iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants received iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15,and 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 42 | 40 | 43 | 41 |
| Mean (Standard Error) [Units on a scale] |
7.30
(1.85)
|
9.27
(1.91)
|
6.32
(1.82)
|
0.15
(1.87)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | All Treated Participants, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 7.15 | |
| Confidence Interval |
(2-Sided) 95% 1.97 to 12.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Abatacept 10/10, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 9.12 | |
| Confidence Interval |
(2-Sided) 95% 3.83 to 14.41 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Abatacept 3/3, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 6.17 | |
| Confidence Interval |
(2-Sided) 95% 1.01 to 11.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Short-term Period: Number of Participants Achieving a Reduction of At Least 0.3 Unit From Baseline in HAQ-DI Scores at Day 169 |
|---|---|
| Description | The HAQ-DI assesses a participant's ability to perform the following tasks: dress/groom; arise; eat; walk; reach; grip; maintain hygiene; and maintain daily activity over a period by marking their response on a questionnaire. Responses/scores range from: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=to unable to do. Higher total score=greater disability. |
| Time Frame | At Day 169 from Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 infusion of study medication at any time. Missing response values were imputed as nonresponders for participants who discontinued early after receiving study medication. |
| Arm/Group Title | Abatacept 30/10 | Abatacept 10/10 | Abatacept 3/3 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received iv infusions of abatacept (30 mg/kg - calculated dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg. | Participants received iv infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg and participants weighing >100 kg received 1000mg). | Participants received iv infusions of abatacept (3 mg/kg - calculated dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants received iv infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. |
| Measure Participants | 43 | 40 | 45 | 42 |
| Number [Participants] |
15
34.9%
|
18
45%
|
16
35.6%
|
8
19%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | All Treated Participants, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 16.0 | |
| Confidence Interval |
(2-Sided) 95% -2.5 to 34.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference and 95% CI was based on CMH with stratification of baseline BSA affected by psoriasis. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Abatacept 10/10, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 26.1 | |
| Confidence Interval |
() 95% 6.8 to 45.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference and 95% CI was based on CMH with stratification of baseline BSA affected by psoriasis. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Abatacept 3/3, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 16.6 | |
| Confidence Interval |
() 95% -1.8 to 34.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference and 95% CI was based on CMH with stratification of baseline BSA affected by psoriasis. | |
Adverse Events
| Time Frame | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Abatacept 10/10 (Short-term Period) | Abatacept 3/3 (Short-term Period) | Abatacept 30/10 (Short-term Period) | Abatacept (Long-term Period) | Placebo (Short-term Period) | |||||
| Arm/Group Description | Participants received IV infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg). | Participants received IV infusions of abatacept (3 mg/kg, calculated-dose) over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. All participants received calculated dose based on their screening visit weight. | Participants received IV infusions of abatacept (30 mg/kg, calculated-dose) over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed-dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. All participants received a calculated dose on Days 1 and 15 followed by fixed dose based on their screening visit weight (participants weighing <60 kg received 500 mg, 60 to 100 kg received 750 mg, and >100 kg received 1000 mg. | Participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days. | Participants received IV infusions of either dextrose 5% solution or 0.9% sodium chloride solution at a constant rate over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. | |||||
All Cause Mortality |
||||||||||
| Abatacept 10/10 (Short-term Period) | Abatacept 3/3 (Short-term Period) | Abatacept 30/10 (Short-term Period) | Abatacept (Long-term Period) | Placebo (Short-term Period) | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| Abatacept 10/10 (Short-term Period) | Abatacept 3/3 (Short-term Period) | Abatacept 30/10 (Short-term Period) | Abatacept (Long-term Period) | Placebo (Short-term Period) | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/40 (5%) | 1/45 (2.2%) | 4/43 (9.3%) | 20/147 (13.6%) | 1/42 (2.4%) | |||||
| Cardiac disorders | ||||||||||
| Acute coronary syndrome | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Aortic valve incompetence | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Atrial fibrillation | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 2/147 (1.4%) | 0/42 (0%) | |||||
| Cardiac failure | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Gastritis | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Hepatobiliary disorders | ||||||||||
| Cholecystitis acute | 0/40 (0%) | 0/45 (0%) | 1/43 (2.3%) | 0/147 (0%) | 0/42 (0%) | |||||
| Immune system disorders | ||||||||||
| Anaphylactic reaction | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Infections and infestations | ||||||||||
| Cellulitis | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Gastroenteritis | 1/40 (2.5%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Herpes zoster | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Osteomyelitis | 0/40 (0%) | 0/45 (0%) | 1/43 (2.3%) | 0/147 (0%) | 0/42 (0%) | |||||
| Pneumonia | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 2/147 (1.4%) | 0/42 (0%) | |||||
| Pyelonephritis acute | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Sinusitis | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Humerus fracture | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Overdose | 0/40 (0%) | 0/45 (0%) | 1/43 (2.3%) | 0/147 (0%) | 0/42 (0%) | |||||
| Tendon rupture | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthritis | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 2/147 (1.4%) | 0/42 (0%) | |||||
| Groin pain | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Intervertebral disc protrusion | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Osteoarthritis | 0/40 (0%) | 1/45 (2.2%) | 0/43 (0%) | 3/147 (2%) | 0/42 (0%) | |||||
| Psoriatic arthropathy | 0/40 (0%) | 1/45 (2.2%) | 0/43 (0%) | 0/147 (0%) | 0/42 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Basal cell carcinoma | 0/40 (0%) | 0/45 (0%) | 1/43 (2.3%) | 0/147 (0%) | 0/42 (0%) | |||||
| Bowen's disease | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Lentigo maligna stage unspecified | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Nervous system disorders | ||||||||||
| Dizziness | 1/40 (2.5%) | 0/45 (0%) | 0/43 (0%) | 0/147 (0%) | 0/42 (0%) | |||||
| Migraine | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Personality disorder | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 1/42 (2.4%) | |||||
| Renal and urinary disorders | ||||||||||
| Urinary retention | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Apnoea | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Asthma | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Psoriasis | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 0/42 (0%) | |||||
| Social circumstances | ||||||||||
| Family stress | 0/40 (0%) | 0/45 (0%) | 0/43 (0%) | 1/147 (0.7%) | 1/42 (2.4%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Abatacept 10/10 (Short-term Period) | Abatacept 3/3 (Short-term Period) | Abatacept 30/10 (Short-term Period) | Abatacept (Long-term Period) | Placebo (Short-term Period) | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/40 (40%) | 15/45 (33.3%) | 16/43 (37.2%) | 73/147 (49.7%) | 19/42 (45.2%) | |||||
| Gastrointestinal disorders | ||||||||||
| Diarrhoea | 3/40 (7.5%) | 0/45 (0%) | 0/43 (0%) | 8/147 (5.4%) | 2/42 (4.8%) | |||||
| Nausea | 2/40 (5%) | 1/45 (2.2%) | 2/43 (4.7%) | 6/147 (4.1%) | 3/42 (7.1%) | |||||
| General disorders | ||||||||||
| Chest pain | 1/40 (2.5%) | 0/45 (0%) | 1/43 (2.3%) | 10/147 (6.8%) | 1/42 (2.4%) | |||||
| Fatigue | 3/40 (7.5%) | 1/45 (2.2%) | 1/43 (2.3%) | 3/147 (2%) | 1/42 (2.4%) | |||||
| Infections and infestations | ||||||||||
| Bronchitis | 1/40 (2.5%) | 0/45 (0%) | 3/43 (7%) | 13/147 (8.8%) | 1/42 (2.4%) | |||||
| Nasopharyngitis | 4/40 (10%) | 5/45 (11.1%) | 4/43 (9.3%) | 33/147 (22.4%) | 4/42 (9.5%) | |||||
| Sinusitis | 2/40 (5%) | 1/45 (2.2%) | 2/43 (4.7%) | 12/147 (8.2%) | 2/42 (4.8%) | |||||
| Upper respiratory tract infection | 1/40 (2.5%) | 3/45 (6.7%) | 2/43 (4.7%) | 16/147 (10.9%) | 2/42 (4.8%) | |||||
| Urinary tract infection | 0/40 (0%) | 2/45 (4.4%) | 0/43 (0%) | 10/147 (6.8%) | 0/42 (0%) | |||||
| Nervous system disorders | ||||||||||
| Headache | 1/40 (2.5%) | 3/45 (6.7%) | 4/43 (9.3%) | 9/147 (6.1%) | 4/42 (9.5%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 0/40 (0%) | 1/45 (2.2%) | 3/43 (7%) | 8/147 (5.4%) | 1/42 (2.4%) | |||||
| Vascular disorders | ||||||||||
| Hypertension | 3/40 (7.5%) | 1/45 (2.2%) | 1/43 (2.3%) | 7/147 (4.8%) | 1/42 (2.4%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
| Name/Title | BMS Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00534313
Other Study ID Numbers:
- IM101-158
- EUDRACT 2007-004241-15
First Posted:
Sep 24, 2007
Last Update Posted:
Aug 1, 2012
Last Verified:
Jul 1, 2012