Trial Outcomes & Findings for Study of Abatacept Versus Placebo to Assess the Prevention of Rheumatoid Arthritis (RA) in Adult Patients (NCT NCT00124449)
NCT ID: NCT00124449
Last Updated: 2015-04-07
Results Overview
ARA criteria is a 7-item tool for RA classification purposes; a patient is said to have RA (meeting endpoint) if he or she has satisfied at least 4 of the 7 criteria. If a participant discontinued due to lack of efficacy, he/she was regarded as meeting primary endpoint also.
COMPLETED
PHASE2
56 participants
12 months
2015-04-07
Participant Flow
184 participants were screened, 127 were enrolled but not randomized (5 withdrew consent; 120 no longer met study criteria; 2 other reasons). 57 participants were randomized, 1 participant was randomized but not treated.
Participant milestones
| Measure |
Abatacept
Abatacept by intravenous (IV) infusion, dose based on participant's body weight at the screening visit
|
Placebo
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
6-month Double-Blind Treatment Period
STARTED
|
28
|
28
|
|
6-month Double-Blind Treatment Period
COMPLETED
|
22
|
17
|
|
6-month Double-Blind Treatment Period
NOT COMPLETED
|
6
|
11
|
|
18-Month Untreated Observation Period
STARTED
|
22
|
17
|
|
18-Month Untreated Observation Period
Completed Year 1 of Study
|
14
|
9
|
|
18-Month Untreated Observation Period
COMPLETED
|
7
|
4
|
|
18-Month Untreated Observation Period
NOT COMPLETED
|
15
|
13
|
Reasons for withdrawal
| Measure |
Abatacept
Abatacept by intravenous (IV) infusion, dose based on participant's body weight at the screening visit
|
Placebo
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
6-month Double-Blind Treatment Period
Adverse Event
|
1
|
0
|
|
6-month Double-Blind Treatment Period
Lack of Efficacy
|
3
|
8
|
|
6-month Double-Blind Treatment Period
Withdrawal by Subject
|
1
|
1
|
|
6-month Double-Blind Treatment Period
Poor/Noncompliance
|
1
|
0
|
|
6-month Double-Blind Treatment Period
Sponsor request
|
0
|
1
|
|
6-month Double-Blind Treatment Period
Exposure to mycobacterium tuberculosis
|
0
|
1
|
|
18-Month Untreated Observation Period
Adverse Event
|
0
|
1
|
|
18-Month Untreated Observation Period
Lack of Efficacy
|
11
|
12
|
|
18-Month Untreated Observation Period
Lost to Follow-up
|
1
|
0
|
|
18-Month Untreated Observation Period
Pregnancy
|
1
|
0
|
|
18-Month Untreated Observation Period
Poor/Noncompliance
|
1
|
0
|
|
18-Month Untreated Observation Period
Relocated
|
1
|
0
|
Baseline Characteristics
Study of Abatacept Versus Placebo to Assess the Prevention of Rheumatoid Arthritis (RA) in Adult Patients
Baseline characteristics by cohort
| Measure |
Abatacept
n=28 Participants
Abatacept by IV infusion, dose based on participant's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
Total
n=56 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.5 years
n=5 Participants
|
44.0 years
n=7 Participants
|
44.0 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
25 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
North America
|
6 participants
n=5 Participants
|
5 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Region of Enrollment
South America
|
5 participants
n=5 Participants
|
2 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Region of Enrollment
Europe
|
17 participants
n=5 Participants
|
21 participants
n=7 Participants
|
38 participants
n=5 Participants
|
|
Months of Undifferentiated Inflammatory Arthritis (UA)
|
8.8 Months
STANDARD_DEVIATION 4.2 • n=5 Participants
|
7.1 Months
STANDARD_DEVIATION 4.4 • n=7 Participants
|
7.9 Months
STANDARD_DEVIATION 4.3 • n=5 Participants
|
|
Weight
|
75.9 Kilograms
STANDARD_DEVIATION 22.5 • n=5 Participants
|
70.9 Kilograms
STANDARD_DEVIATION 13.9 • n=7 Participants
|
73.4 Kilograms
STANDARD_DEVIATION 18.7 • n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: Randomized and treated participants were included in analysis if they were RA positive and/or were discontinued due to lack of efficacy. (Those who discontinued due to reasons other than lack of efficacy in 1-year window were excluded from the analysis). 1 participant in Placebo group was excluded due to presence of RA at baseline.
ARA criteria is a 7-item tool for RA classification purposes; a patient is said to have RA (meeting endpoint) if he or she has satisfied at least 4 of the 7 criteria. If a participant discontinued due to lack of efficacy, he/she was regarded as meeting primary endpoint also.
Outcome measures
| Measure |
Abatacept
n=26 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=24 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Number of Participants With a Diagnosis of Rheumatoid Arthritis (RA) by American Rheumatism Association (ARA) Criteria and/or Discontinued Due to Lack of Efficacy
|
12 Participants
|
16 Participants
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: Randomized and treated participants were included in analysis if they were RA positive and/or were discontinued due to lack of efficacy. (Those who discontinued due to reasons other than lack of efficacy in 2-year window were excluded from the analysis). 1 subject in the Placebo group is excluded due to presence of RA at baseline.
ARA criteria is a 7-item tool for classification purposes; a patient is said to have RA (meeting endpoint) if he or she has satisfied at least 4 of the 7 criteria. If a participant discontinued due to lack of efficacy, he/she was regarded as meeting endpoint also.
Outcome measures
| Measure |
Abatacept
n=23 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=24 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Number of Participants With a Diagnosis of RA by 1987 ARA Criteria and/or Discontinued Due to Lack of Efficacy
|
17 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: 12 months, 24 monthsPopulation: n=Randomized and treated participants who were RA positive and/or were discontinued due to lack of efficacy. (Those who discontinued due to reasons other than lack of efficacy in the 1- or 2-year window were excluded from the analysis).1 participant in Placebo group was excluded due to the presence of RA at baseline.
Clinical diagnosis of other rheumatic diseases at 12 and 24 months. If a participant discontinued due to lack of efficacy, he/she was regarded as meeting endpoint also.
Outcome measures
| Measure |
Abatacept
n=28 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Number of Participants With Undifferentiated Inflammatory Arthritis (UA) Who Develop Another Rheumatic Disease
12 months (n=26; n=24)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Undifferentiated Inflammatory Arthritis (UA) Who Develop Another Rheumatic Disease
24 months (n=23; n=24)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, 6 months, 12 months, 24 monthsPopulation: n=participants with a score at baseline and at timepoint
Mean change from baseline using the Genant-Modified Sharp Score. Erosion score=assessment of 14 sites in each hand and wrist + 6 joints in each foot, using an 8-point scale from 0 (no erosions) to 3.5 (erosions of 100% or articular surfaces). Joint score= assessment of 13 sites in each wrist and hand + 6 sites in each foot using a 9-point scale from 0 (normal) to 4.0 (definite ankylosis). As-observed data. Change from Baseline=postbaseline score at timepoint (6 or 12 or 24 months) minus baseline score; a lower value signifies improvement.
Outcome measures
| Measure |
Abatacept
n=28 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Change From Baseline in Radiographic Erosion and Joint Space Narrowing Score at 6 Months, 12 Months, and 24 Months
Erosion Score 6 months (n=22; n=21)
|
0.13 units on a scale
Standard Error 0.09
|
0.46 units on a scale
Standard Error 0.24
|
|
Change From Baseline in Radiographic Erosion and Joint Space Narrowing Score at 6 Months, 12 Months, and 24 Months
Joint Space Narrowing 6 months (n=22; n=21)
|
0.00 units on a scale
Standard Error 0.00
|
0.01 units on a scale
Standard Error 0.01
|
|
Change From Baseline in Radiographic Erosion and Joint Space Narrowing Score at 6 Months, 12 Months, and 24 Months
Total Score 6 months (n=22; n=21)
|
0.13 units on a scale
Standard Error 0.09
|
0.47 units on a scale
Standard Error 0.24
|
|
Change From Baseline in Radiographic Erosion and Joint Space Narrowing Score at 6 Months, 12 Months, and 24 Months
Erosion Score 12 months (n=17; n=11)
|
0.02 units on a scale
Standard Error 0.04
|
0.85 units on a scale
Standard Error 0.39
|
|
Change From Baseline in Radiographic Erosion and Joint Space Narrowing Score at 6 Months, 12 Months, and 24 Months
Joint Space Narrowing 12 months (n=17; n=11)
|
0.00 units on a scale
Standard Error 0.00
|
0.26 units on a scale
Standard Error 0.22
|
|
Change From Baseline in Radiographic Erosion and Joint Space Narrowing Score at 6 Months, 12 Months, and 24 Months
Total Score 12 months (n=17; n=11)
|
0.02 units on a scale
Standard Error 0.04
|
1.11 units on a scale
Standard Error 0.56
|
|
Change From Baseline in Radiographic Erosion and Joint Space Narrowing Score at 6 Months, 12 Months, and 24 Months
Erosion Score 24 months (n=7; n=3)
|
0.04 units on a scale
Standard Error 0.04
|
-0.17 units on a scale
Standard Error 0.17
|
|
Change From Baseline in Radiographic Erosion and Joint Space Narrowing Score at 6 Months, 12 Months, and 24 Months
Joint Space Narrowing 24 months (n=7; n=3)
|
0.00 units on a scale
Standard Error 0.00
|
0.00 units on a scale
Standard Error 0.00
|
|
Change From Baseline in Radiographic Erosion and Joint Space Narrowing Score at 6 Months, 12 Months, and 24 Months
Total Score 24 months (n=7; n=3)
|
0.04 units on a scale
Standard Error 0.04
|
-0.17 units on a scale
Standard Error 0.17
|
SECONDARY outcome
Timeframe: Baseline, 6 months, 12 months, 24 monthsPopulation: All randomized and treated participants (n=number of participants with baseline and postbaseline measurements). MRIs were done only in participants at European Union sites.
Mean change from baseline. Degree of synovitis and structural joint damage (erosion, edema) of the carpal and metacarpophalangeal joints, as measured by magnetic resonance imaging (MRI) scores using the European League Against Rheumatism (EULAR)-Outcome Measures in Rheumatology Clinical Trials (OMERACT) assessment. Edema scale=0 (no bone involved) to 3 (67% to 100% of bone involved). Synovitis scale=0 (normal) and 1-3 (mild, moderate, severe. Bone erosion scale=0 (0% of bone involved) to 10 (91% to 100% of bone involved). Change from baseline=postbaseline score at timepoint - baseline score.
Outcome measures
| Measure |
Abatacept
n=28 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Change From Baseline in Total Erosion, Edema, Synovitis Scores at 6 Months, 12 Months, and 24 Months
Erosion Score at 6 months (n=11; n=10)
|
0.45 units on a scale
Standard Error 0.37
|
1.20 units on a scale
Standard Error 1.09
|
|
Change From Baseline in Total Erosion, Edema, Synovitis Scores at 6 Months, 12 Months, and 24 Months
Edema Score at 6 months (n=11; n=10)
|
-1.64 units on a scale
Standard Error 1.48
|
1.40 units on a scale
Standard Error 1.59
|
|
Change From Baseline in Total Erosion, Edema, Synovitis Scores at 6 Months, 12 Months, and 24 Months
Synovitis Score at 6 months (n=11; n=10)
|
0.27 units on a scale
Standard Error 0.56
|
1.60 units on a scale
Standard Error 1.23
|
|
Change From Baseline in Total Erosion, Edema, Synovitis Scores at 6 Months, 12 Months, and 24 Months
Erosion Score at 12 months (n=9; n=6)
|
0.00 units on a scale
Standard Error 0.17
|
5.00 units on a scale
Standard Error 3.20
|
|
Change From Baseline in Total Erosion, Edema, Synovitis Scores at 6 Months, 12 Months, and 24 Months
Edema Score at 12 months (n=9; n=6)
|
0.22 units on a scale
Standard Error 0.49
|
6.67 units on a scale
Standard Error 4.22
|
|
Change From Baseline in Total Erosion, Edema, Synovitis Scores at 6 Months, 12 Months, and 24 Months
Synovitis Score at 12 months (n=9; n=6)
|
0.22 units on a scale
Standard Error 0.22
|
2.33 units on a scale
Standard Error 1.61
|
|
Change From Baseline in Total Erosion, Edema, Synovitis Scores at 6 Months, 12 Months, and 24 Months
Erosion Score at 24 months (n=5; n=2)
|
0.80 units on a scale
Standard Error 0.49
|
0.00 units on a scale
Standard Error 0.00
|
|
Change From Baseline in Total Erosion, Edema, Synovitis Scores at 6 Months, 12 Months, and 24 Months
Edema Score at 24 months (n=5; n=2)
|
0.20 units on a scale
Standard Error 0.20
|
0.50 units on a scale
Standard Error 0.50
|
|
Change From Baseline in Total Erosion, Edema, Synovitis Scores at 6 Months, 12 Months, and 24 Months
Synovitis Score at 24 months (n=5; n=2)
|
0.60 units on a scale
Standard Error 0.60
|
1.50 units on a scale
Standard Error 2.50
|
SECONDARY outcome
Timeframe: 6, 12, and 24 monthsPopulation: All randomized and treated participants (n=number of participants with assessment at baseline and timepoint)
Synovitis, assessed by clinical signs and symptoms
Outcome measures
| Measure |
Abatacept
n=28 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Number of Participants With Persistent Symptomatic Clinical Synovitis
6 months (n=5; n=12)
|
4 Participants
|
12 Participants
|
|
Number of Participants With Persistent Symptomatic Clinical Synovitis
12 months (n=11; n=7)
|
10 Participants
|
7 Participants
|
|
Number of Participants With Persistent Symptomatic Clinical Synovitis
24 months (n=3; n=2)
|
3 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 6 months, 12 months, 24 monthsPopulation: All randomized and treated participants (n=number of participants with baseline and postbaseline measurements)
SF-36, a 36-item instrument that covers 8 quality of life domains, which were used to derive the physical and mental component summary scores, which ranged from 0 to 100, with higher scores indicating a better quality of life. Change from baseline=postbaseline - baseline value; a higher value signifies improvement.
Outcome measures
| Measure |
Abatacept
n=28 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) Scores - Mean Change From Baseline
PCS, 6 months (n=26; n=20)
|
10.23 units on a scale
Standard Error 1.68
|
1.95 units on a scale
Standard Error 1.52
|
|
Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) Scores - Mean Change From Baseline
MCS, 6 months (n=26; n=20)
|
2.54 units on a scale
Standard Error 1.33
|
-0.30 units on a scale
Standard Error 1.29
|
|
Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) Scores - Mean Change From Baseline
PCS, 12 months (n=20; n=14)
|
3.83 units on a scale
Standard Error 2.38
|
-0.81 units on a scale
Standard Error 2.26
|
|
Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) Scores - Mean Change From Baseline
MCS, 12 months (n=20; n=14)
|
2.50 units on a scale
Standard Error 1.75
|
-2.89 units on a scale
Standard Error 2.85
|
|
Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) Scores - Mean Change From Baseline
PCS, 24 months (n=7; n=5)
|
2.46 units on a scale
Standard Error 3.15
|
-2.17 units on a scale
Standard Error 6.44
|
|
Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) Scores - Mean Change From Baseline
MCS, 24 months (n=7; n=5)
|
3.75 units on a scale
Standard Error 1.99
|
-3.30 units on a scale
Standard Error 7.58
|
SECONDARY outcome
Timeframe: Baseline, 6 Months, 12 months, 24 monthsPopulation: All randomized and treated participants (n=number of participants with baseline and postbaseline measurements).
To assess pharmacodynamic effect of abatacept on serum levels of autoantibodies, mean change from baseline in cytokines (interleukin-6 \[IL-6\], interleukin-1B \[IL-1B\], tumor necrosis factor Alpha \[TNF-Alpha\], Matrix Metalloproteinase 3T \[MMP3T\], and anti-CCP2), as measured by standard laboratory investigations, were assessed. Change from baseline=postbaseline value at timepoint (6 or 12 or 24 months) minus baseline value; a lower value signifies improvement.
Outcome measures
| Measure |
Abatacept
n=28 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
IL6 at 6 months (n=19, n=18)
|
-4.49 laboratory values
Standard Error 1.78
|
1.08 laboratory values
Standard Error 0.72
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
IL6 at 12 months (n=13, n=7)
|
-0.14 laboratory values
Standard Error 1.61
|
6.37 laboratory values
Standard Error 3.81
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
IL6 at 24 months (n=5, n=3)
|
-3.44 laboratory values
Standard Error 3.54
|
0.90 laboratory values
Standard Error 1.51
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
IL1B at 6 months (n=18, n=18)
|
-0.12 laboratory values
Standard Error 0.07
|
-0.09 laboratory values
Standard Error 0.08
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
IL1B at 12 months (n=13, n=7)
|
-0.09 laboratory values
Standard Error 0.07
|
-0.24 laboratory values
Standard Error 0.21
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
IL1B at 24 months (n=5, n=1)
|
0.20 laboratory values
Standard Error 0.20
|
0.00 laboratory values
Standard Error 0.00
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
TNF-Alpha at 6 months (n=18, n=18)
|
-1.70 laboratory values
Standard Error 1.29
|
0.07 laboratory values
Standard Error 0.28
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
TNF-Alpha at 12 months (n=13, n=7)
|
-0.50 laboratory values
Standard Error 0.25
|
-0.10 laboratory values
Standard Error 0.33
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
TNF-Alpha at 24 months (n=13, n=7)
|
-0.82 laboratory values
Standard Error 0.47
|
-0.03 laboratory values
Standard Error 0.03
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
MMP3T at 6 months (n=20, n=19)
|
-2.29 laboratory values
Standard Error 4.86
|
14.34 laboratory values
Standard Error 9.85
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
MMP3T at 12 months (n=15, n=9)
|
-2.55 laboratory values
Standard Error 3.08
|
25.34 laboratory values
Standard Error 14.59
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
MMP3T at 24 months (n=6, n=3)
|
6.73 laboratory values
Standard Error 6.93
|
3.10 laboratory values
Standard Error 3.45
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
Anti-CCP2 antibodies at 6 months (n=21, n=19)
|
-94.5 laboratory values
Standard Error 29.49
|
16.32 laboratory values
Standard Error 21.49
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
Anti-CCP2 antibodies at 12 months (n=14, n=10)
|
-6.46 laboratory values
Standard Error 48.09
|
149.5 laboratory values
Standard Error 64.38
|
|
Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months
Anti-CCP2 antibodies at 24 months (n=6, n=3)
|
3.43 laboratory values
Standard Error 53.85
|
-35.1 laboratory values
Standard Error 55.65
|
SECONDARY outcome
Timeframe: Day 1, 6 months, 12 months, 24 monthsPopulation: All randomized and treated participants (n=number of participants with measure at timepoint).
To assess the pharmacodynamic effect of abatacept on serum levels of autoantibodies, number of participants with Anti-CCP2 Positive of Rheumatoid Factor (RF) positive
Outcome measures
| Measure |
Abatacept
n=28 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Number of Participants With Anti-CCP2 Positive and/or Rheumatoid Factor (RF) Positive Over Time
Anti-CCP2 Positive on Day 1 (n=28, n=28)
|
28 Participants
|
28 Participants
|
|
Number of Participants With Anti-CCP2 Positive and/or Rheumatoid Factor (RF) Positive Over Time
Anti-CCP2 Positive at 6 months (n=22, n=19)
|
20 Participants
|
19 Participants
|
|
Number of Participants With Anti-CCP2 Positive and/or Rheumatoid Factor (RF) Positive Over Time
Anti-CCP2 Positive at 12 months (n=15, n=10)
|
13 Participants
|
10 Participants
|
|
Number of Participants With Anti-CCP2 Positive and/or Rheumatoid Factor (RF) Positive Over Time
Anti-CCP2 Positive at 24 months (n=6, n=3)
|
5 Participants
|
3 Participants
|
|
Number of Participants With Anti-CCP2 Positive and/or Rheumatoid Factor (RF) Positive Over Time
RF on Day 1 (n=28, n=28)
|
24 Participants
|
20 Participants
|
|
Number of Participants With Anti-CCP2 Positive and/or Rheumatoid Factor (RF) Positive Over Time
RF at 6 months (n=22, n=20)
|
13 Participants
|
14 Participants
|
|
Number of Participants With Anti-CCP2 Positive and/or Rheumatoid Factor (RF) Positive Over Time
RF at 12 months (n=15, n=10)
|
11 Participants
|
8 Participants
|
|
Number of Participants With Anti-CCP2 Positive and/or Rheumatoid Factor (RF) Positive Over Time
RF at 24 months (n=6, n=3)
|
3 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Day 1Population: All randomized and treated participants
To assess the pharmacodynamic effect of abatacept on serum levels of autoantibodies, a blood sample was obtained for HLA typing to determine the presence or absence of alleles associated with RA susceptibility and severity (shared epitope alleles HLA-DRB10401 and HLA-DRB10404).
Outcome measures
| Measure |
Abatacept
n=28 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Frequency of Human Leukocyte Antigen (HLA) Typing
Missing
|
4 participants
|
7 participants
|
|
Frequency of Human Leukocyte Antigen (HLA) Typing
Undetected
|
11 participants
|
10 participants
|
|
Frequency of Human Leukocyte Antigen (HLA) Typing
Detected
|
13 participants
|
11 participants
|
SECONDARY outcome
Timeframe: 6 months, 12 months, 24 monthsPopulation: All randomized and treated participants (n=the number of participants with baseline and postbaseline measurements).
The DAS 28 (CRP) is a composite of 4 variables: 28 tender joint count, 28 swollen joint count, CRP, and subject assessment of disease activity measure on a VAS of 100 mm. Change from Baseline=postbaseline score-baseline score; a lower value signifies improvement.
Outcome measures
| Measure |
Abatacept
n=28 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
DAS 28 C Reactive Protein (CRP) Score - Mean Change From Baseline
6 Months (n=20; n=20)
|
-1.13 units on a scale
Standard Error 0.20
|
0.01 units on a scale
Standard Error 0.26
|
|
DAS 28 C Reactive Protein (CRP) Score - Mean Change From Baseline
12 Months (n=18; n=13)
|
-0.50 units on a scale
Standard Error 0.22
|
-0.05 units on a scale
Standard Error 0.42
|
|
DAS 28 C Reactive Protein (CRP) Score - Mean Change From Baseline
24 Months (n=6; n=4)
|
-0.33 units on a scale
Standard Error 0.33
|
0.69 units on a scale
Standard Error 1.16
|
SECONDARY outcome
Timeframe: 6 months, 12 months, 24 monthsPopulation: All randomized and treated participants (n=the number of participants with baseline and postbaseline measurements).
The DAS 28 (CRP) is a composite of 4 variables: tender joint count, swollen joint count, CRP, and subject assessment of disease activity measure on a VAS of 100 mm. Scores for disease activity are defined as low (≤ 3.2) and in remission (\< 2.6).
Outcome measures
| Measure |
Abatacept
n=28 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Number of Participants With a DAS 28 (CRP) Score of ≤3.2 (Low Disease Activity) or <2.6 (in Remission)
≤3.2 at 6 months (n=21; n=20)
|
17 Participants
|
9 Participants
|
|
Number of Participants With a DAS 28 (CRP) Score of ≤3.2 (Low Disease Activity) or <2.6 (in Remission)
<2.6 at 6 months (n=21; n=20)
|
15 Participants
|
7 Participants
|
|
Number of Participants With a DAS 28 (CRP) Score of ≤3.2 (Low Disease Activity) or <2.6 (in Remission)
≤3.2 at 12 months (n=19; n=13)
|
13 Participants
|
7 Participants
|
|
Number of Participants With a DAS 28 (CRP) Score of ≤3.2 (Low Disease Activity) or <2.6 (in Remission)
<2.6 at 12 months (n=19; n=13)
|
9 Participants
|
5 Participants
|
|
Number of Participants With a DAS 28 (CRP) Score of ≤3.2 (Low Disease Activity) or <2.6 (in Remission)
≤3.2 at 24 months (n=7; n=4)
|
5 Participants
|
2 Participants
|
|
Number of Participants With a DAS 28 (CRP) Score of ≤3.2 (Low Disease Activity) or <2.6 (in Remission)
<2.6 at 24 months (n=7; n=4)
|
4 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 6 months, 12 months, 24 monthsPopulation: All randomized and treated participants (n=the number of participants with baseline and postbaseline measurements).
This questionnaire includes 20 questions assessing physical function in 8 domains. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. Higher scores indicate greater dysfunction. HAQ response =improvement of at least 0.3 units from baseline.
Outcome measures
| Measure |
Abatacept
n=28 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Number of Subjects With Health Assessment Questionnaire (HAQ) Disability Index Response
6 Months (n=26; n=25)
|
16 Participants
|
6 Participants
|
|
Number of Subjects With Health Assessment Questionnaire (HAQ) Disability Index Response
12 months (n=25; n=25)
|
9 Participants
|
3 Participants
|
|
Number of Subjects With Health Assessment Questionnaire (HAQ) Disability Index Response
24 months (n=21; n=24)
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Throughout the treatment period (6 months)Population: All subjects who received at least 1 dose of study medication
AEs were monitored at all scheduled visits of the study drug treatment and observation periods and at the follow-up visits performed 28, 56, and 85 days after the last infusion of study medication for participants who were withdrawn prematurely
Outcome measures
| Measure |
Abatacept
n=28 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
n=28 Participants
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Overall Safety - Adverse Events (AEs), Serious AEs, and Deaths
Deaths
|
0 Participants
|
0 Participants
|
|
Overall Safety - Adverse Events (AEs), Serious AEs, and Deaths
SAEs
|
1 Participants
|
1 Participants
|
|
Overall Safety - Adverse Events (AEs), Serious AEs, and Deaths
AEs
|
18 Participants
|
20 Participants
|
|
Overall Safety - Adverse Events (AEs), Serious AEs, and Deaths
Related AEs
|
14 Participants
|
10 Participants
|
|
Overall Safety - Adverse Events (AEs), Serious AEs, and Deaths
Discontinued due to AEs
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to 12 monthsImmunogenicity, as measured by the number of positive repsonses for serum levels of abatacept-specific antibodies measured by enzyme-linked immunosorbent assays (ELISA). Postive response for whole molecule assessment was a value of \> 400 and for tip assessment was ≥25.
Outcome measures
| Measure |
Abatacept
n=27 Participants
Abatacept by intravenous (IV) infusion, dose based on subject's body weight at the screening visit
|
Placebo
Placebo (dextrose 5% in water \[D5W\] or normal saline \[NS\]) by IV infusion.
|
|---|---|---|
|
Number of Participants With Positive Responses for Serum Levels of Abatacept-specific Antibodies
|
4 participants
|
—
|
Adverse Events
BMS-188667
Placebo
Serious adverse events
| Measure |
BMS-188667
n=28 participants at risk
|
Placebo
n=28 participants at risk
|
|---|---|---|
|
Nervous system disorders
SCIATICA
|
0.00%
0/28
|
3.6%
1/28
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
|
3.6%
1/28
|
0.00%
0/28
|
Other adverse events
| Measure |
BMS-188667
n=28 participants at risk
|
Placebo
n=28 participants at risk
|
|---|---|---|
|
Nervous system disorders
HEADACHE
|
10.7%
3/28
|
7.1%
2/28
|
|
Gastrointestinal disorders
NAUSEA
|
0.00%
0/28
|
7.1%
2/28
|
|
Gastrointestinal disorders
VOMITING
|
7.1%
2/28
|
0.00%
0/28
|
|
Gastrointestinal disorders
DIARRHOEA
|
14.3%
4/28
|
10.7%
3/28
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/28
|
7.1%
2/28
|
|
Infections and infestations
RHINITIS
|
0.00%
0/28
|
7.1%
2/28
|
|
Infections and infestations
SINUSITIS
|
7.1%
2/28
|
0.00%
0/28
|
|
Infections and infestations
PHARYNGITIS
|
7.1%
2/28
|
0.00%
0/28
|
|
Infections and infestations
GASTROENTERITIS
|
0.00%
0/28
|
10.7%
3/28
|
|
Infections and infestations
NASOPHARYNGITIS
|
10.7%
3/28
|
7.1%
2/28
|
|
Infections and infestations
URINARY TRACT INFECTION
|
7.1%
2/28
|
10.7%
3/28
|
|
Skin and subcutaneous tissue disorders
ECZEMA
|
7.1%
2/28
|
0.00%
0/28
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
7.1%
2/28
|
0.00%
0/28
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
7.1%
2/28
|
7.1%
2/28
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
7.1%
2/28
|
0.00%
0/28
|
|
Respiratory, thoracic and mediastinal disorders
PHARYNGOLARYNGEAL PAIN
|
3.6%
1/28
|
14.3%
4/28
|
|
General disorders
PAIN
|
0.00%
0/28
|
7.1%
2/28
|
|
General disorders
CHILLS
|
0.00%
0/28
|
7.1%
2/28
|
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