Trial Outcomes & Findings for Safety and Efficacy of Abatacept Versus Placebo in Participants With Psoriatic Arthritis (NCT NCT00534313)
NCT ID: NCT00534313
Last Updated: 2012-08-01
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
191 participants
Primary outcome timeframe
From Day 169 to Day 729
Results posted on
2012-08-01
Participant Flow
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).
Participant milestones
| Measure |
Abatacept 30/10
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.
|
Abatacept 10/10
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).
|
Abatacept 3/3
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.
|
Placebo
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.
|
|---|---|---|---|---|
|
Short-term Period
STARTED
|
43
|
40
|
45
|
42
|
|
Short-term Period
COMPLETED
|
37
|
34
|
43
|
33
|
|
Short-term Period
NOT COMPLETED
|
6
|
6
|
2
|
9
|
|
Long-term Period
STARTED
|
37
|
34
|
43
|
33
|
|
Long-term Period
COMPLETED
|
0
|
0
|
0
|
0
|
|
Long-term Period
NOT COMPLETED
|
37
|
34
|
43
|
33
|
Reasons for withdrawal
| Measure |
Abatacept 30/10
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.
|
Abatacept 10/10
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).
|
Abatacept 3/3
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.
|
Placebo
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.
|
|---|---|---|---|---|
|
Short-term Period
Adverse Event
|
1
|
2
|
1
|
3
|
|
Short-term Period
Lack of Efficacy
|
3
|
4
|
0
|
3
|
|
Short-term Period
Participant not meeting study criteria
|
0
|
0
|
0
|
1
|
|
Short-term Period
Participant withdrew consent
|
2
|
0
|
0
|
2
|
|
Short-term Period
Pregnancy
|
0
|
0
|
1
|
0
|
|
Long-term Period
Adverse Event
|
2
|
1
|
0
|
1
|
|
Long-term Period
Lack of Efficacy
|
14
|
10
|
14
|
12
|
|
Long-term Period
Lost to Follow-up
|
1
|
2
|
0
|
0
|
|
Long-term Period
Withdrawal by Subject
|
2
|
2
|
0
|
0
|
|
Long-term Period
No longer meets study criteria
|
0
|
1
|
0
|
0
|
|
Long-term Period
Poor compliance/noncompliance
|
0
|
1
|
1
|
0
|
|
Long-term Period
Administrative reason by sponsor
|
17
|
15
|
26
|
18
|
|
Long-term Period
Other
|
1
|
2
|
2
|
2
|
Baseline Characteristics
Safety and Efficacy of Abatacept Versus Placebo in Participants With Psoriatic Arthritis
Baseline characteristics by cohort
| Measure |
Abatacept 30/10
n=43 Participants
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.
|
Abatacept 10/10
n=40 Participants
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).
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
n=42 Participants
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
n=170 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
|
54.0 years
n=5 Participants
|
51.5 years
n=7 Participants
|
51.0 years
n=5 Participants
|
53.0 years
n=4 Participants
|
52.0 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
79 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
91 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
43 participants
n=5 Participants
|
38 participants
n=7 Participants
|
44 participants
n=5 Participants
|
41 participants
n=4 Participants
|
166 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
3 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Pacific
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
Weight
|
92.9 kilograms
STANDARD_DEVIATION 21.3 • n=5 Participants
|
85.0 kilograms
STANDARD_DEVIATION 17.9 • n=7 Participants
|
85.0 kilograms
STANDARD_DEVIATION 19.1 • n=5 Participants
|
96.0 kilograms
STANDARD_DEVIATION 19.4 • n=4 Participants
|
89.7 kilograms
STANDARD_DEVIATION 19.9 • n=21 Participants
|
PRIMARY outcome
Timeframe: From Day 169 to Day 729Population: All participants who received at least 1 infusion of abatacept during the long-term period.
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.
Outcome measures
| Measure |
All Treated Participants
n=147 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
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.
|
Abatacept 3/3
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.
|
Placebo
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.
|
|---|---|---|---|---|
|
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
Deaths
|
0 Participants
|
—
|
—
|
—
|
|
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
SAEs
|
20 Participants
|
—
|
—
|
—
|
|
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
Drug-related SAEs
|
4 Participants
|
—
|
—
|
—
|
|
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
SAEs leading to discontinuation
|
0 Participants
|
—
|
—
|
—
|
|
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
AEs
|
123 Participants
|
—
|
—
|
—
|
|
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
Drug-related AEs
|
58 Participants
|
—
|
—
|
—
|
|
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
AES leading to discontinuation
|
4 Participants
|
—
|
—
|
—
|
|
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
AEs of Interest (AEI): Infections
|
83 Participants
|
—
|
—
|
—
|
|
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
AEI: Malignancy
|
2 Participants
|
—
|
—
|
—
|
|
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
AEI: Autoimmune disorders (presp)
|
5 Participants
|
—
|
—
|
—
|
|
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
AEI: Infusion reactions (presp): Acute
|
4 Participants
|
—
|
—
|
—
|
|
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
AEI: Infusion reactions (presp): Periinfusional
|
11 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: At Day 169 from BaselinePopulation: 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.
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.
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
n=42 Participants
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.
|
|---|---|---|---|---|
|
Short-term Period: Number of Participants With ACR 20 Response at Day 169
|
18 Participants
|
19 Participants
|
15 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: At Days 365 and 729 from BaselinePopulation: All participants who received at least 1 infusion of abatacept in the long-term (open-label) period. (n=number of participants with a response)
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.
Outcome measures
| Measure |
All Treated Participants
n=37 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=34 Participants
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.
|
Abatacept 3/3
n=43 Participants
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.
|
Placebo
n=33 Participants
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.
|
|---|---|---|---|---|
|
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
ACR 20, Day 365 (n=34, 29, 36, 32)
|
50.0 Percentage of participants
Interval 33.2 to 66.8
|
62.1 Percentage of participants
Interval 44.4 to 79.7
|
61.1 Percentage of participants
Interval 45.2 to 77.0
|
46.9 Percentage of participants
Interval 29.6 to 64.2
|
|
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
ACR 20, Day 729 (n=21, 18, 26, 18)
|
81 Percentage of participants
Interval 64.2 to 97.7
|
66.7 Percentage of participants
Interval 44.9 to 88.4
|
65.4 Percentage of participants
Interval 47.1 to 83.7
|
72.2 Percentage of participants
Interval 51.5 to 92.9
|
|
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
ACR 50, Day 365 (n=34, 29, 36, 32)
|
23.5 Percentage of participants
Interval 9.3 to 37.8
|
37.9 Percentage of participants
Interval 20.3 to 55.6
|
33.3 Percentage of participants
Interval 17.9 to 48.7
|
34.4 Percentage of participants
Interval 17.9 to 50.8
|
|
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
ACR 50, Day 729 (n=21, 18, 26, 18)
|
57.1 Percentage of participants
Interval 36.0 to 78.3
|
27.8 Percentage of participants
Interval 7.1 to 48.5
|
42.3 Percentage of participants
Interval 23.3 to 61.3
|
55.6 Percentage of participants
Interval 32.6 to 78.5
|
|
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
ACR 70, Day 365 (n=34, 29, 36, 32)
|
5.9 Percentage of participants
Interval 0.0 to 13.8
|
17.2 Percentage of participants
Interval 3.5 to 31.01
|
13.9 Percentage of participants
Interval 2.6 to 25.2
|
18.8 Percentage of participants
Interval 5.2 to 32.2
|
|
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
ACR 70, Day 729 (n=21, 18, 26, 18)
|
23.8 Percentage of participants
Interval 5.6 to 42.0
|
16.7 Percentage of participants
Interval 0.0 to 33.9
|
23.1 Percentage of participants
Interval 6.9 to 39.3
|
11.1 Percentage of participants
Interval 0.0 to 25.6
|
|
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
ACR 90, Day 365 (n=34, 29, 36, 32)
|
0 Percentage of participants
Interval 0.0 to 0.0
|
6.9 Percentage of participants
Interval 0.0 to 16.1
|
5.6 Percentage of participants
Interval 0.0 to 13.0
|
6.3 Percentage of participants
Interval 0.0 to 14.6
|
|
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
ACR 90, Day 729 (n=21, 18, 26, 18)
|
0 Percentage of participants
Interval 0.0 to 0.0
|
5.6 Percentage of participants
Interval 0.0 to 16.1
|
11.5 Percentage of participants
Interval 0.0 to 23.8
|
0 Percentage of participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: From Day 169 to Days 365 and 729Population: All participants who received at least 1 infusion of abatacept in the long-term (open-label) period. (n=number of participants with a response)
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).
Outcome measures
| Measure |
All Treated Participants
n=37 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=34 Participants
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.
|
Abatacept 3/3
n=43 Participants
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.
|
Placebo
n=33 Participants
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.
|
|---|---|---|---|---|
|
Long-term Period: Number of Participants With an Investigators Global Assessment (IGA) Score of Clear or Almost Clear at Days 365 and 729
Day 365 (n=30, 29, 34, 23)
|
13 Participants
|
10 Participants
|
19 Participants
|
10 Participants
|
|
Long-term Period: Number of Participants With an Investigators Global Assessment (IGA) Score of Clear or Almost Clear at Days 365 and 729
Day 729 (n=20, 17, 26, 18)
|
10 Participants
|
7 Participants
|
16 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: From Baseline to Days 365 and 729Population: All participants who received at least 1 infusion of abatacept in the long-term (open-label) period.
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.
Outcome measures
| Measure |
All Treated Participants
n=37 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=34 Participants
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.
|
Abatacept 3/3
n=43 Participants
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.
|
Placebo
n=33 Participants
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.
|
|---|---|---|---|---|
|
Long-term Period: Mean Percentage of Change From Baseline in Target Lesion Score at Days 365 and 729
Day 729
|
49.14 Percentage of change
Standard Deviation 9.13
|
45.07 Percentage of change
Standard Deviation 7.98
|
44.79 Percentage of change
Standard Deviation 9.09
|
34.41 Percentage of change
Standard Deviation 8.98
|
|
Long-term Period: Mean Percentage of Change From Baseline in Target Lesion Score at Days 365 and 729
Day 365
|
27.51 Percentage of change
Standard Deviation 7.92
|
41.97 Percentage of change
Standard Deviation 7.90
|
20.32 Percentage of change
Standard Deviation 8.59
|
33.82 Percentage of change
Standard Deviation 7.52
|
SECONDARY outcome
Timeframe: At Days 365 and 729 from baselinePCS=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.
Outcome measures
| Measure |
All Treated Participants
n=37 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=34 Participants
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.
|
Abatacept 3/3
n=43 Participants
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.
|
Placebo
n=33 Participants
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.
|
|---|---|---|---|---|
|
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
Day 365 PCS (n=34, 32, 37,29)
|
1.73 Units on a scale
Standard Error 1.10
|
7.59 Units on a scale
Standard Error 1.36
|
4.86 Units on a scale
Standard Error 1.67
|
3.59 Units on a scale
Standard Error 1.19
|
|
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
Day 365 MCS (n=34,32, 37,29)
|
2.73 Units on a scale
Standard Error 1.60
|
1.07 Units on a scale
Standard Error 2.00
|
4.95 Units on a scale
Standard Error 2.10
|
4.40 Units on a scale
Standard Error 2.00
|
|
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
Day 729 PCS (n=20,18, 26,18)
|
5.59 Units on a scale
Standard Error 1.43
|
7.97 Units on a scale
Standard Error 2.0
|
6.74 Units on a scale
Standard Error 1.95
|
4.45 Units on a scale
Standard Error 1.14
|
|
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
Day 729 MCS (n=20,18, 26,18)
|
5.89 Units on a scale
Standard Error 1.84
|
-0.17 Units on a scale
Standard Error 2.71
|
1.85 Units on a scale
Standard Error 2.11
|
4.35 Units on a scale
Standard Error 2.29
|
SECONDARY outcome
Timeframe: Days 365 and 729 from baselinePopulation: All participants who received at least 1 infusion of abatacept in the long-term (open-label) period. (n=number of participants with responses available)
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.
Outcome measures
| Measure |
All Treated Participants
n=37 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=34 Participants
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.
|
Abatacept 3/3
n=43 Participants
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.
|
Placebo
n=33 Participants
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.
|
|---|---|---|---|---|
|
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
Day 365 (n=3, 28, 32, 23)
|
12 Participants
|
16 Participants
|
17 Participants
|
12 Participants
|
|
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
Day 729 (n=9, 11, 13, 10)
|
9 Participants
|
11 Participants
|
13 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: From Baseline to Day 169Population: 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).
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.
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
n=42 Participants
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.
|
|---|---|---|---|---|
|
Short-term Period: Number of Participants With Marked Abnormalities in Hematology
Platelet count (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Hematology
Hemoglobin (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Hematology
Hematocrit (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Hematology
Erythrocytes (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Baseline to Day 169Population: 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).
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.
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
n=42 Participants
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.
|
|---|---|---|---|---|
|
Short-term Period: Number of Participants With Marked Abnormalities in Hematology (Continued)
Leukocytes (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Hematology (Continued)
Neutrophils+bands (absolute) (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Hematology (Continued)
Lymphocytes (absolute) (n = 43, 40, 45, 41)
|
2 Participants
|
0 Participants
|
6 Participants
|
1 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Hematology (Continued)
Monocytes (absolute) (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Hematology (Continued)
Basophils (absolute) (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Hematology (Continued)
Eosinophils (absolute) (n = 43, 40, 45, 41)
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline to Day 169Population: 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).
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.
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
n=42 Participants
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.
|
|---|---|---|---|---|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry
ALP (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry
AST (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry
ALT (n = 43, 40, 45, 41)
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry
GGT (n = 43, 40, 45, 41)
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry
Bilirubin (total) (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry
BUN (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry
Creatinine (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline to Day 169Population: 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).
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.
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
n=42 Participants
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.
|
|---|---|---|---|---|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)
Sodium (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)
Potassium (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)
Chloride (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)
Calcium (total) (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)
Phosphorous , inorganic (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From Baseline to Day 169Population: All participants who received at least 1 infusion of study medication during the double-blind period. n=number of participants with evaluable results.
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.
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
n=42 Participants
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.
|
|---|---|---|---|---|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)
Glucose (n = 43, 40, 45, 41)
|
1 Participants
|
4 Participants
|
8 Participants
|
2 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)
Glucose, fasting (n = 16, 12, 12, 15)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)
Protein (total) (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)
Albumin (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)
Uric acid (n = 43, 40, 45, 41)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Baseline to Day 169Population: 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).
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).
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
n=42 Participants
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.
|
|---|---|---|---|---|
|
Short-term Period: Number of Participants With Marked Abnormalities in Urinalysis
Protein (n = 42, 37, 38, 40)
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Urinalysis
Glucose (n = 42, 37, 38, 40)
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Urinalysis
Blood (n = 42, 37, 38, 40)
|
2 Participants
|
2 Participants
|
3 Participants
|
2 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Urinalysis
Leukocyte esterase (n = 3, 7, 4, 5)
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Urinalysis
WBC (n = 6, 8, 8, 6)
|
1 Participants
|
1 Participants
|
3 Participants
|
3 Participants
|
|
Short-term Period: Number of Participants With Marked Abnormalities in Urinalysis
RBC (n = 6, 7, 5, 6)
|
3 Participants
|
1 Participants
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: From Baseline to Day 169Population: All participants who received at least 1 infusion of study medication during the double-blind period.
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.
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
n=42 Participants
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.
|
|---|---|---|---|---|
|
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
Deaths
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
SAEs
|
4 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
|
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
AEs
|
29 Participants
|
31 Participants
|
31 Participants
|
30 Participants
|
|
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
All AEs Leading to Discontinuation
|
1 Participants
|
2 Participants
|
1 Participants
|
3 Participants
|
|
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
All SAEs Leading to Discontinuation
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
Drug-related AEs
|
13 Participants
|
13 Participants
|
12 Participants
|
7 Participants
|
|
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
Drug-related SAEs
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At Day 169 from BaselinePopulation: 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.
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).
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
n=42 Participants
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.
|
|---|---|---|---|---|
|
Short-term Period: Number of Participants With an IGA Score of Clear or Almost Clear at Day 169
|
9 Participants
|
10 Participants
|
17 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: At Day 169 from BaselinePopulation: 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.
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.
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
n=42 Participants
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.
|
|---|---|---|---|---|
|
Short-term Period: Mean Percentage of Change From Baseline in Target Lesion Score at Day 169
|
19.39 Percentage of change
Standard Error 9.16
|
22.96 Percentage of change
Standard Error 9.46
|
31.11 Percentage of change
Standard Error 8.98
|
0.63 Percentage of change
Standard Error 9.35
|
SECONDARY outcome
Timeframe: From Baseline to Day 169Population: Participants who received abatacept and for whom baseline and at least 1 additional measurement were available during the double-blind (short-term) period.
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 \[anti-abatacept antibody\].
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
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.
|
|---|---|---|---|---|
|
Short-term Period: Number of Participants With Positive Responses for Serum Levels of Abatacept-specific Antibodies (Anti-Abatacept-C)
|
1 Participants
|
0 Participants
|
2 Participants
|
—
|
SECONDARY outcome
Timeframe: At Day 169 from BaselinePopulation: 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.
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.
Outcome measures
| Measure |
All Treated Participants
n=42 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=43 Participants
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.
|
Placebo
n=41 Participants
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.
|
|---|---|---|---|---|
|
Short-term Period: Mean Change From Baseline in the Mental Component Summary Score as Measured by the Short-form 36 at Day 169
|
4.50 Units on a scale
Standard Error 2.45
|
4.42 Units on a scale
Standard Error 2.50
|
3.16 Units on a scale
Standard Error 2.41
|
2.41 Units on a scale
Standard Error 2.47
|
SECONDARY outcome
Timeframe: Days 1, 15, 29, 57, 85, 113, 141, and 169Population: 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.
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.
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
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.
|
|---|---|---|---|---|
|
Short-term Period: Mean Serum Concentrations of Abatacept
Day 1 (n= 13, 13, 44)
|
0 µg/mL
Standard Deviation 0
|
0.01 µg/mL
Standard Deviation 0.01
|
0 µg/mL
Standard Deviation 0
|
—
|
|
Short-term Period: Mean Serum Concentrations of Abatacept
Day 15 (n= 43, 38, 42)
|
119.99 µg/mL
Standard Deviation 35.30
|
48.29 µg/mL
Standard Deviation 17.96
|
14.28 µg/mL
Standard Deviation 7.67
|
—
|
|
Short-term Period: Mean Serum Concentrations of Abatacept
Day 29 (n= 41, 39, 43)
|
186.82 µg/mL
Standard Deviation 62.49
|
49.70 µg/mL
Standard Deviation 16.79
|
16.20 µg/mL
Standard Deviation 4.86
|
—
|
|
Short-term Period: Mean Serum Concentrations of Abatacept
Day 57 (n= 40, 39, 44)
|
58.55 µg/mL
Standard Deviation 26.09
|
25.75 µg/mL
Standard Deviation 9.67
|
10.42 µg/mL
Standard Deviation 5.75
|
—
|
|
Short-term Period: Mean Serum Concentrations of Abatacept
Day 85 (n= 37, 35, 41)
|
39.00 µg/mL
Standard Deviation 19.37
|
26.29 µg/mL
Standard Deviation 10.59
|
8.73 µg/mL
Standard Deviation 3.26
|
—
|
|
Short-term Period: Mean Serum Concentrations of Abatacept
Day 113 ( n= 35, 33, 43)
|
36.30 µg/mL
Standard Deviation 19.94
|
32.69 µg/mL
Standard Deviation 14.08
|
8.85 µg/mL
Standard Deviation 5.01
|
—
|
|
Short-term Period: Mean Serum Concentrations of Abatacept
Day 141 (n= 35, 34, 42)
|
26.70 µg/mL
Standard Deviation 9.24
|
25.78 µg/mL
Standard Deviation 9.74
|
7.66 µg/mL
Standard Deviation 3.13
|
—
|
|
Short-term Period: Mean Serum Concentrations of Abatacept
Day 169 (n= 36, 42, 34)
|
28.93 µg/mL
Standard Deviation 11.29
|
26.34 µg/mL
Standard Deviation 10.75
|
9.29 µg/mL
Standard Deviation 5.23
|
—
|
SECONDARY outcome
Timeframe: Days 1, 15, 29, 57, 85, 113, 141, and 169Population: 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.
Abatacept was assayed using a validated ELISA method. Cmin of abatacept was obtained from concentration versus time data.
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
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.
|
|---|---|---|---|---|
|
Short-term Period: Mean Serum Trough Concentrations (Cmin) of Abatacept
Day 141 (n= 35, 34, 42)
|
25.02 µg/mL
Interval 10.77 to 43.31
|
23.62 µg/mL
Interval 7.24 to 45.66
|
6.91 µg/mL
Interval 1.5 to 14.32
|
—
|
|
Short-term Period: Mean Serum Trough Concentrations (Cmin) of Abatacept
Day 15 (n= 43, 38, 43)
|
115.35 µg/mL
Interval 70.65 to 236.39
|
45.10 µg/mL
Interval 21.27 to 95.96
|
12.81 µg/mL
Interval 4.25 to 39.81
|
—
|
|
Short-term Period: Mean Serum Trough Concentrations (Cmin) of Abatacept
Day 29 (n= 41, 39, 43)
|
176.22 µg/mL
Interval 68.45 to 373.07
|
46.86 µg/mL
Interval 21.23 to 87.55
|
15.43 µg/mL
Interval 4.99 to 28.15
|
—
|
|
Short-term Period: Mean Serum Trough Concentrations (Cmin) of Abatacept
Day 57 (n= 40, 39, 44)
|
53.08 µg/mL
Interval 11.21 to 151.1
|
23.88 µg/mL
Interval 8.18 to 50.84
|
9.03 µg/mL
Interval 2.53 to 33.88
|
—
|
|
Short-term Period: Mean Serum Trough Concentrations (Cmin) of Abatacept
Day 85 (n= 37, 35, 41)
|
33.09 µg/mL
Interval 1.87 to 94.46
|
24.36 µg/mL
Interval 10.47 to 55.13
|
8.15 µg/mL
Interval 2.97 to 16.01
|
—
|
|
Short-term Period: Mean Serum Trough Concentrations (Cmin) of Abatacept
Day 113 (n= 35, 33, 43)
|
31.50 µg/mL
Interval 8.3 to 78.91
|
29.60 µg/mL
Interval 6.66 to 71.21
|
7.56 µg/mL
Interval 2.14 to 27.82
|
—
|
|
Short-term Period: Mean Serum Trough Concentrations (Cmin) of Abatacept
Day 169 (n= 36, 34, 42)
|
26.65 µg/mL
Interval 10.05 to 53.77
|
24.33 µg/mL
Interval 11.65 to 50.31
|
7.84 µg/mL
Interval 1.68 to 28.85
|
—
|
SECONDARY outcome
Timeframe: Days 1, 15, 29, 57, 85, 113, 141, and 169PK 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At Day 169 from BaselinePopulation: 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.
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.
Outcome measures
| Measure |
All Treated Participants
n=42 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=43 Participants
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.
|
Placebo
n=41 Participants
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.
|
|---|---|---|---|---|
|
Short-term Period: Mean Change From Baseline in Physical Component Summary Score as Measured by the Short-form 36 at Day 169
|
7.30 Units on a scale
Standard Error 1.85
|
9.27 Units on a scale
Standard Error 1.91
|
6.32 Units on a scale
Standard Error 1.82
|
0.15 Units on a scale
Standard Error 1.87
|
SECONDARY outcome
Timeframe: At Day 169 from BaselinePopulation: 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.
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.
Outcome measures
| Measure |
All Treated Participants
n=43 Participants
Long-term period: All participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Abatacept 10/10
n=40 Participants
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.
|
Abatacept 3/3
n=45 Participants
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.
|
Placebo
n=42 Participants
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.
|
|---|---|---|---|---|
|
Short-term Period: Number of Participants Achieving a Reduction of At Least 0.3 Unit From Baseline in HAQ-DI Scores at Day 169
|
15 Participants
|
18 Participants
|
16 Participants
|
8 Participants
|
Adverse Events
Abatacept 10/10 (Short-term Period)
Serious events: 2 serious events
Other events: 16 other events
Deaths: 0 deaths
Abatacept 3/3 (Short-term Period)
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Abatacept 30/10 (Short-term Period)
Serious events: 4 serious events
Other events: 16 other events
Deaths: 0 deaths
Abatacept (Long-term Period)
Serious events: 20 serious events
Other events: 73 other events
Deaths: 0 deaths
Placebo (Short-term Period)
Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Abatacept 10/10 (Short-term Period)
n=40 participants at risk
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).
|
Abatacept 3/3 (Short-term Period)
n=45 participants at risk
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.
|
Abatacept 30/10 (Short-term Period)
n=43 participants at risk
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.
|
Abatacept (Long-term Period)
n=147 participants at risk
Participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Placebo (Short-term Period)
n=42 participants at risk
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.
|
|---|---|---|---|---|---|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Cardiac disorders
Aortic valve incompetence
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
1.4%
2/147
|
0.00%
0/42
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/40
|
0.00%
0/45
|
2.3%
1/43
|
0.00%
0/147
|
0.00%
0/42
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Infections and infestations
Cellulitis
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Infections and infestations
Gastroenteritis
|
2.5%
1/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/40
|
0.00%
0/45
|
2.3%
1/43
|
0.00%
0/147
|
0.00%
0/42
|
|
Infections and infestations
Pneumonia
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
1.4%
2/147
|
0.00%
0/42
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Infections and infestations
Sinusitis
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/40
|
0.00%
0/45
|
2.3%
1/43
|
0.00%
0/147
|
0.00%
0/42
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
1.4%
2/147
|
0.00%
0/42
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/40
|
2.2%
1/45
|
0.00%
0/43
|
2.0%
3/147
|
0.00%
0/42
|
|
Musculoskeletal and connective tissue disorders
Psoriatic arthropathy
|
0.00%
0/40
|
2.2%
1/45
|
0.00%
0/43
|
0.00%
0/147
|
0.00%
0/42
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/40
|
0.00%
0/45
|
2.3%
1/43
|
0.00%
0/147
|
0.00%
0/42
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lentigo maligna stage unspecified
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Nervous system disorders
Dizziness
|
2.5%
1/40
|
0.00%
0/45
|
0.00%
0/43
|
0.00%
0/147
|
0.00%
0/42
|
|
Nervous system disorders
Migraine
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Psychiatric disorders
Personality disorder
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
2.4%
1/42
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Respiratory, thoracic and mediastinal disorders
Apnoea
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
0.00%
0/42
|
|
Social circumstances
Family stress
|
0.00%
0/40
|
0.00%
0/45
|
0.00%
0/43
|
0.68%
1/147
|
2.4%
1/42
|
Other adverse events
| Measure |
Abatacept 10/10 (Short-term Period)
n=40 participants at risk
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).
|
Abatacept 3/3 (Short-term Period)
n=45 participants at risk
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.
|
Abatacept 30/10 (Short-term Period)
n=43 participants at risk
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.
|
Abatacept (Long-term Period)
n=147 participants at risk
Participants received an open-label abatacept weight-tiered dose of 10 mg/kg at Day 169 and every 28 days.
|
Placebo (Short-term Period)
n=42 participants at risk
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.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
7.5%
3/40
|
0.00%
0/45
|
0.00%
0/43
|
5.4%
8/147
|
4.8%
2/42
|
|
Gastrointestinal disorders
Nausea
|
5.0%
2/40
|
2.2%
1/45
|
4.7%
2/43
|
4.1%
6/147
|
7.1%
3/42
|
|
General disorders
Chest pain
|
2.5%
1/40
|
0.00%
0/45
|
2.3%
1/43
|
6.8%
10/147
|
2.4%
1/42
|
|
General disorders
Fatigue
|
7.5%
3/40
|
2.2%
1/45
|
2.3%
1/43
|
2.0%
3/147
|
2.4%
1/42
|
|
Infections and infestations
Bronchitis
|
2.5%
1/40
|
0.00%
0/45
|
7.0%
3/43
|
8.8%
13/147
|
2.4%
1/42
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
4/40
|
11.1%
5/45
|
9.3%
4/43
|
22.4%
33/147
|
9.5%
4/42
|
|
Infections and infestations
Sinusitis
|
5.0%
2/40
|
2.2%
1/45
|
4.7%
2/43
|
8.2%
12/147
|
4.8%
2/42
|
|
Infections and infestations
Upper respiratory tract infection
|
2.5%
1/40
|
6.7%
3/45
|
4.7%
2/43
|
10.9%
16/147
|
4.8%
2/42
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/40
|
4.4%
2/45
|
0.00%
0/43
|
6.8%
10/147
|
0.00%
0/42
|
|
Nervous system disorders
Headache
|
2.5%
1/40
|
6.7%
3/45
|
9.3%
4/43
|
6.1%
9/147
|
9.5%
4/42
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/40
|
2.2%
1/45
|
7.0%
3/43
|
5.4%
8/147
|
2.4%
1/42
|
|
Vascular disorders
Hypertension
|
7.5%
3/40
|
2.2%
1/45
|
2.3%
1/43
|
4.8%
7/147
|
2.4%
1/42
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER