Substudy - Low Dose of Abatacept in Subjects With Rheumatoid Arthritis
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00989235
Collaborator
(none)
108
2
30
Study Details
Study Description
Brief Summary
The purpose of this exploratory sub-study was to evaluate from a clinical perspective the impact on disease activity of lowering the dose of abatacept from 10 mg/kg to 5 mg/kg in subjects who had achieved remission (Disease Activity Score 28 [DAS 28]-erythrocyte sedimentation rate [ESR] < 2.6) at Day 701 of study IM101023.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
108 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3B, Multi-Center, Randomized, Double-blind Study to Evaluate Remission and Joint Damage Progression in Methotrexate-naïve Early Erosive Rheumatoid Arthritis Subjects Treated With Abatacept Plus Methotrexate Compared With Methotrexate - Low Dose Sub-Study
Study Start Date
:
Apr 1, 2007
Actual Primary Completion Date
:
Oct 1, 2009
Actual Study Completion Date
:
Oct 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Abatacept (10 mg/Kg)
|
Drug: Abatacept
IV solution, IV, 10 mg/Kg, Once monthly, 1 year
Other Names:
|
| Active Comparator: Abatacept (5 mg/Kg)
|
Drug: Abatacept
IV solution, IV, 5 mg/Kg, Once monthly, 1 year
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Time to Disease Relapse Through Month 12 (Kaplan-Meier Cumulative Percentage of Events of Disease Relapse) [Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12]
An event of disease relapse was defined as additional Disease-modifying antirheumatic drug (DMARD) therapy given, or 2 or more courses of high steroids given, or return to abatacept 10 mg/kg (rescue medication given), or DAS28 C-reactive protein (CRP) score >=3.2 at 2 consecutive visits. Time to disease relapse was evaluated using life tables (Kaplan-Meier Cumulative Percentage of Events of Disease Relapse).
Secondary Outcome Measures
- Number of Participants Experiencing Disease Relapse [After 12 Months of treatment]
Disease relapse is defined as additional DMARD therapy given, or 2 or more courses of high steroids given, or return to abatacept 10 mg/kg (rescue medication given), or DAS28 CRP score >= 3.2 at 2 consecutive visits.
- Mean Time-Matched Baseline DAS28 CRP Scores [Baseline]
Mean baseline DAS28 CRP values for the cohort of participants with serum samples available at that timepoint. DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a visual analogue scale (VAS) of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission).
- Adjusted Mean Change From Baseline in DAS28 CRP During Double-Blind Treatment [Baseline, Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365]
Mean baseline DAS28 CRP values for the cohort of participants with serum samples available at that timepoint. DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a VAS of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission).
- Percentage of Participants With 2 Consecutive DAS 28 CRP Scores ≥ 3.2 (Loss of Low Disease Activity Status) [After 12 months of treatment]
DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a VAS of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission).
- Percentage of Participants Given Additional DMARD Therapy During Double-Blind Treatment [After 12 months of treatment]
Additional DMARD therapy is defined as a re-introduction of methotrexate (MTX), an increase of at least 2.5 mg of MTX, or the addition of at least 1 DMARD.
- Percentage of Participants Who at Any Time During Double-Blind Treatment Were Given 2 or More Courses of High-Dose Steroids [After 12 months of treatment]
A course of high dose steroids is defined as a course of intramuscular, intravenous, or high dose oral corticosteroids (use of > 10 mg/day equivalent of prednisone for a minimum of 3 consecutive days or for those subjects who had continued use for long durations of time, each course was determined by 28 day intervals).
- Percentage of Participants Given Rescue Medication Therapy During Double-Blind Treatment [After 12 months of treatment]
All subjects in the sub-study randomized to receive double-blind abatacept 5 mg/kg or 10 mg/kg. Subjects rescued to open-label treatment received abatacept 10 mg/kg.
- Percentage of Participants Who Modified Therapy During Double-Blind Treatment [After 12 months of treatment]
Modified therapy=additional DMARD therapy, 2 or more courses of high dose steroids or rescue medication. Additional DMARD therapy=re-introduction of methotrexate (MTX), an increase of at least 2.5 mg of MTX, or the addition of at least 1 DMARD. A course of high dose steroids=a course of intramuscular, intravenous, or high dose oral corticosteroids (use of > 10 mg/day equivalent of prednisone for a minimum of 3 consecutive days or for those subjects who had continued use for long durations of time, each course was determined by 28 day intervals). Rescue medication=abatacept 10 mg/kg.
- Percentage of Participants Who Lost Remission Status [After 12 months of treatment]
Loss of remission is defined as DAS 28 CRP >=2.6.
- Steady-state Trough Serum Concentration (Cmin) of Abatacept During Double-Blind Treatment [Day 701 of the main study; sub-study Days 1, 85, 169, 253]
- Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations During Double-Blind Treatment [From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Related AE/SAE=Certain, Probable, Possible, or Missing. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
- Percentage of Participants With Infection and Infestation AEs Reported During Double-Blind Treatment [From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Infection and Infestation AEs = any AE within the System Organ Class Infection and Infestation.
- Percentage of Participants With Malignant Neoplasms Reported During Double-Blind Treatment [From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)]
All neoplasms were assessed by medical review as to whether or not the event was malignant.
- Percentage of Participants With Prespecified Acute Infusional Adverse Events (AIAEs) During Double-Blind Treatment, by Intensity [From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Acute Infusional AE= a subset of the peri-infusional AEs with onset during the first hour after the start of the study drug infusion. A total of 105 infusional events were prespecified in the protocol.
- Percentage of Participants With Prespecified Peri-Infusional Adverse Events (PAIAEs) During Double-Blind Treatment, by Intensity [From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Peri-infusional AE=a pre-specified infusional AE occuring during the first 24 hours after the start of study drug infusion.A total of 105 infusional events were prespecified in the protocol. GDASC=General Disorders and Administration Site Conditions, RTMD=Respiratory, Thoracic and Mediastinal Disorders.
- Percentage of Participants With Pre-specified Autoimmune Disorders (ADs) Reported During Double-Blind Treatment, by Intensity [From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)]
A total of 127 autoimmune disorders were prespecified in the protocol. MCTD=Musculoskeletal and Connective Tissue Disorders
- Percentage of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During Double-Blind Treatment [From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)]
Not evaluated: high hemoglobin,high hematocrit,high erythrocytes,high neutrophils+bands(N+B),low monocytes,low basophils,low eosinophils,low alkaline phosphatase(ALP),low aspartate aminotransferase(AST),low alanine aminotransferase(ALT),low G-Glutamyl transferase(GGT),low total bilirubin,low blood urea nitrogen,low creatinine,high albumin,low uric acid,low urine protein,low urine glucose,low urine blood,low urine leukocyte esterase,low urine white blood cells,low red blood cells.Pre Rx=pretreatment,(*)Lymphocytes(c/uL):Low<.750x10^3,High>7.50x10^3.(*)Eosinophils:>.750x10^3 c/uL.
- Clinically Significant Changes in Vital Signs and Physical Findings [From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)]
Clinical significance was determined by investigator. Parameters include blood pressure, heart rate, respiration rate, and temperature.
- Participants With Positive Antibody Responses to Abatacept (Electrochemiluminescence [ECL] Method) During Double-Blind Treatment [After 12 months of treatment]
A positive antibody response to Abatacept (measured by the ECL assay) is further classified as a positive response for either Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Possibly immunoglobulin (Ig)' or 'Ig and/or Junction Region'
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Subjects who have completed the main study, are willing to participate and have a DAS 28 ESR score of < 2.6 on Day 701 of the main study
Exclusion Criteria:
- None
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00989235
Other Study ID Numbers:
- IM101-023 LT (Sub study)
- Eudrac # 2002-000784-26
First Posted:
Oct 5, 2009
Last Update Posted:
Jun 21, 2011
Last Verified:
Jun 1, 2011
Keywords provided by ,
,
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | IM101023 (NCT00122382) was a 2-year study completing on Day 729, in which subjects were randomized to receive abatacept or placebo in combination with methotrexate (MTX) for the 1st year of the study and were then switched to open-label abatacept+MTX in the 2nd year. All subjects had received abatacept for a least 1 year prior start of sub-study. |
|---|---|
| Pre-assignment Detail | Of the 433 participants who completed the main study (IM101-023 NCT00122382), 108 enrolled in the sub-study. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All subjects in the sub-study randomized to receive double-blind abatacept 10 mg/kg. Subjects rescued to open-label treatment received abatacept 10 mg/kg. The length of the sub-study is 1 year. As such, the maximum time the subject is treated collectively in double-blind and open-label treatment is 1 year. | All subjects in the sub-study randomized to receive double-blind abatacept 5 mg/kg. Subjects rescued to open-label treatment received abatacept 10 mg/kg. The length of the sub-study is 1 year. As such, the maximum time the subject is treated collectively in double-blind and open-label treatment is 1 year. |
| Period Title: Overall Study | ||
| STARTED | 58 | 50 |
| Number Rescued to Open-Label Treatment | 4 | 4 |
| Number Completing Double-Blind Treatment | 51 | 41 |
| COMPLETED | 55 | 44 |
| NOT COMPLETED | 3 | 6 |
Baseline Characteristics
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) | Total |
|---|---|---|---|
| Arm/Group Description | All participants in the sub-study randomized to receive double-blind abatacept 10 mg/kg | All participants in the sub-study randomized to receive double-blind abatacept 5 mg/kg | Total of all reporting groups |
| Overall Participants | 58 | 50 | 108 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
50.1
(11.5)
|
51.1
(13.4)
|
50.6
(12.3)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
44
75.9%
|
41
82%
|
85
78.7%
|
| Male |
14
24.1%
|
9
18%
|
23
21.3%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Unknown |
2
3.4%
|
0
0%
|
2
1.9%
|
| White |
49
84.5%
|
46
92%
|
95
88%
|
| Black |
2
3.4%
|
0
0%
|
2
1.9%
|
| Asian |
2
3.4%
|
2
4%
|
4
3.7%
|
| Other |
3
5.2%
|
2
4%
|
5
4.6%
|
| Weight (kg) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg] |
72.9
(14.7)
|
73.8
(16.0)
|
73.4
(15.3)
|
| Disease Activity Scores Using C-reactive Protein (DAS 28 [CRP]) (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
2.1
(0.6)
|
2.1
(0.6)
|
2.1
(0.6)
|
Outcome Measures
| Title | Number of Participants Experiencing Disease Relapse |
|---|---|
| Description | Disease relapse is defined as additional DMARD therapy given, or 2 or more courses of high steroids given, or return to abatacept 10 mg/kg (rescue medication given), or DAS28 CRP score >= 3.2 at 2 consecutive visits. |
| Time Frame | After 12 Months of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed=number randomized. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study randomized to receive double-blind abatacept 10 mg/kg | All participants in the sub-study randomized to receive double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Number [Participants] |
18
31%
|
17
34%
|
| Title | Mean Time-Matched Baseline DAS28 CRP Scores |
|---|---|
| Description | Mean baseline DAS28 CRP values for the cohort of participants with serum samples available at that timepoint. DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a visual analogue scale (VAS) of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission). |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed=number of participants randomized; n=All treated participants with available DAS28 CRP scores at that time point. Mean time-matched baseline values reflect changing n-values over time. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study randomized to receive double-blind abatacept 10 mg/kg | All participants in the sub-study randomized to receive double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Day 29 Cohort (n=45, 40) |
2.09
(0.61)
|
2.05
(0.60)
|
| Day 57 Cohort (n=47, 37) |
2.06
(0.59)
|
2.06
(0.62)
|
| Day 85 Cohort (n=46, 42) |
2.10
(0.60)
|
2.09
(0.60)
|
| Day 113 Cohort (n=49, 39) |
2.06
(0.61)
|
2.09
(0.62)
|
| Day 141 Cohort (n=47, 40) |
2.09
(0.59)
|
2.10
(0.62)
|
| Day 169 Cohort (n=46, 36) |
2.10
(0.59)
|
2.04
(0.61)
|
| Day 197 Cohort (n=44, 38) |
2.08
(0.60)
|
2.06
(0.61)
|
| Day 225 Cohort (n=44, 38) |
2.09
(0.60)
|
2.08
(0.63)
|
| Day 253 Cohort (n=46, 37) |
2.07
(0.60)
|
2.04
(0.61)
|
| Day 281 Cohort (n=45, 38) |
2.07
(0.61)
|
2.06
(0.61)
|
| Day 309 Cohort (n=45, 37) |
2.10
(0.58)
|
2.08
(0.61)
|
| Day 337 Cohort (n=44, 36) |
2.09
(0.60)
|
2.08
(0.62)
|
| Day 365 Cohort (n=41, 35) |
2.02
(0.60)
|
2.08
(0.60)
|
| Title | Adjusted Mean Change From Baseline in DAS28 CRP During Double-Blind Treatment |
|---|---|
| Description | Mean baseline DAS28 CRP values for the cohort of participants with serum samples available at that timepoint. DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a VAS of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission). |
| Time Frame | Baseline, Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed=number of participants randomized; n=the number of participants with available DAS28 CRP scores at that time point. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study randomized to receive double-blind abatacept 10 mg/kg | All participants in the sub-study randomized to receive double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Day 29 (n=45, 40) |
0.24
(0.10)
|
0.06
(0.10)
|
| Day 57 (n=47, 37) |
0.05
(0.09)
|
0.14
(0.10)
|
| Day 85 (n=46, 42) |
0.13
(0.10)
|
0.21
(0.10)
|
| Day 113 (n=49, 39) |
0.02
(0.09)
|
0.25
(0.10)
|
| Day 141 (n=47, 40) |
0.32
(0.10)
|
0.29
(0.11)
|
| Day 169 (n=46, 36) |
0.13
(0.09)
|
0.26
(0.11)
|
| Day 197 (n=44, 38) |
0.09
(0.09)
|
0.22
(0.09)
|
| Day 225 (n=44, 38) |
0.25
(0.10)
|
0.29
(0.10)
|
| Day 253 (n=46, 37) |
0.23
(0.09)
|
0.14
(0.10)
|
| Day 281 (n=45, 38) |
0.18
(0.08)
|
0.05
(0.09)
|
| Day 309 (n=45, 37) |
0.07
(0.08)
|
0.09
(0.09)
|
| Day 337 (n=44, 36) |
0.26
(0.11)
|
0.29
(0.13)
|
| Day 365 (n=41, 35) |
0.39
(0.11)
|
0.16
(0.12)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 29 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference |
| Estimated Value | 0.18 | |
| Confidence Interval |
(2-Sided) 95% -0.11 to 0.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 57 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.09 | |
| Confidence Interval |
(2-Sided) 95% -0.34 to 0.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 85 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.08 | |
| Confidence Interval |
(2-Sided) 95% -0.37 to 0.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 113 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.23 | |
| Confidence Interval |
(2-Sided) 95% -0.50 to 0.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 141 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.03 | |
| Confidence Interval |
(2-Sided) 95% -0.26 to 0.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 169 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.13 | |
| Confidence Interval |
(2-Sided) 95% -0.41 to 0.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 197 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.12 | |
| Confidence Interval |
(2-Sided) 95% -0.38 to 0.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 225 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.32 to 0.25 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 253 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.08 | |
| Confidence Interval |
(2-Sided) 95% -0.19 to 0.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 281 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.13 | |
| Confidence Interval |
(2-Sided) 95% -0.12 to 0.38 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 309 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.03 | |
| Confidence Interval |
(2-Sided) 95% -0.27 to 0.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 337 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.03 | |
| Confidence Interval |
(2-Sided) 95% -0.37 to 0.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Day 365 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.23 | |
| Confidence Interval |
(2-Sided) 95% -0.09 to 0.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Change from Baseline = Post-baseline - Baseline value. | |
| Title | Percentage of Participants With 2 Consecutive DAS 28 CRP Scores ≥ 3.2 (Loss of Low Disease Activity Status) |
|---|---|
| Description | DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a VAS of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission). |
| Time Frame | After 12 months of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed= number of participants randomized. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study randomized to receive double-blind abatacept 10 mg/kg | All participants in the sub-study randomized to receive double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Number (95% Confidence Interval) [percentage of participants] |
22.4
38.6%
|
22.0
44%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | estimate of difference |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% -17.2 to 18.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Given Additional DMARD Therapy During Double-Blind Treatment |
|---|---|
| Description | Additional DMARD therapy is defined as a re-introduction of methotrexate (MTX), an increase of at least 2.5 mg of MTX, or the addition of at least 1 DMARD. |
| Time Frame | After 12 months of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed= number of participants randomized. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study randomized to receive double-blind abatacept 10 mg/kg | All participants in the sub-study randomized to receive double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Number (95% Confidence Interval) [percentage of participants] |
3.4
5.9%
|
12.0
24%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | estimate of difference |
| Estimated Value | -8.6 | |
| Confidence Interval |
(2-Sided) 95% -20.3 to 3.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who at Any Time During Double-Blind Treatment Were Given 2 or More Courses of High-Dose Steroids |
|---|---|
| Description | A course of high dose steroids is defined as a course of intramuscular, intravenous, or high dose oral corticosteroids (use of > 10 mg/day equivalent of prednisone for a minimum of 3 consecutive days or for those subjects who had continued use for long durations of time, each course was determined by 28 day intervals). |
| Time Frame | After 12 months of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed= number of participants randomized. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study randomized to receive double-blind abatacept 10 mg/kg | All participants in the sub-study randomized to receive double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
| Title | Time to Disease Relapse Through Month 12 (Kaplan-Meier Cumulative Percentage of Events of Disease Relapse) |
|---|---|
| Description | An event of disease relapse was defined as additional Disease-modifying antirheumatic drug (DMARD) therapy given, or 2 or more courses of high steroids given, or return to abatacept 10 mg/kg (rescue medication given), or DAS28 C-reactive protein (CRP) score >=3.2 at 2 consecutive visits. Time to disease relapse was evaluated using life tables (Kaplan-Meier Cumulative Percentage of Events of Disease Relapse). |
| Time Frame | Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed=number of participants randomized. n=number of participants at risk at the end of a specified month. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study randomized to receive double-blind abatacept 10 mg/kg | All participants in the sub-study randomized to receive double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Month 1 (n=55, 49) |
5.17
|
2.00
|
| Month 2 (n=52, 47) |
8.65
|
4.00
|
| Month 3 (n=51, 42) |
10.41
|
12.35
|
| Month 4 (n=50, 38) |
12.17
|
22.78
|
| Month 5 (n=47, 35) |
13.96
|
26.96
|
| Month 6 (n=42, 33) |
23.11
|
31.13
|
| Month 7 (n=41, 32) |
24.94
|
33.22
|
| Month 8 (n=40, 31) |
26.77
|
33.22
|
| Month 9 (n=38, 31) |
30.43
|
33.22
|
| Month 10 (n=37, 31) |
32.27
|
33.22
|
| Month 11 (n=37, 30) |
32.27
|
35.37
|
| Month 12 (n=36, 28) |
32.27
|
35.37
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | Through Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.870 | |
| Confidence Interval |
(2-Sided) 95% 0.45 to 1.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio determined by a Cox proportional hazards model with treatment as the only covariate. | |
| Title | Percentage of Participants Given Rescue Medication Therapy During Double-Blind Treatment |
|---|---|
| Description | All subjects in the sub-study randomized to receive double-blind abatacept 5 mg/kg or 10 mg/kg. Subjects rescued to open-label treatment received abatacept 10 mg/kg. |
| Time Frame | After 12 months of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed= number of participants randomized. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study randomized to receive double-blind abatacept 10 mg/kg | All participants in the sub-study randomized to receive double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Number (95% Confidence Interval) [percentage of participants] |
6.9
11.9%
|
8.0
16%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | estimate of difference |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -12.9 to 10.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Modified Therapy During Double-Blind Treatment |
|---|---|
| Description | Modified therapy=additional DMARD therapy, 2 or more courses of high dose steroids or rescue medication. Additional DMARD therapy=re-introduction of methotrexate (MTX), an increase of at least 2.5 mg of MTX, or the addition of at least 1 DMARD. A course of high dose steroids=a course of intramuscular, intravenous, or high dose oral corticosteroids (use of > 10 mg/day equivalent of prednisone for a minimum of 3 consecutive days or for those subjects who had continued use for long durations of time, each course was determined by 28 day intervals). Rescue medication=abatacept 10 mg/kg. |
| Time Frame | After 12 months of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed= number of participants randomized. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study randomized to receive double-blind abatacept 10 mg/kg | All participants in the sub-study randomized to receive double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Number (95% Confidence Interval) [percentage of participants] |
10.3
17.8%
|
18.0
36%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | estimate of difference |
| Estimated Value | -7.7 | |
| Confidence Interval |
(2-Sided) 95% -22.6 to 7.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Lost Remission Status |
|---|---|
| Description | Loss of remission is defined as DAS 28 CRP >=2.6. |
| Time Frame | After 12 months of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed= number of participants randomized. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study randomized to receive double-blind abatacept 10 mg/kg | All participants in the sub-study randomized to receive double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Number (95% Confidence Interval) [percentage of participants] |
53.4
92.1%
|
64.0
128%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (10 mg/kg), Abatacept (5 mg/kg) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | estimate of difference |
| Estimated Value | -10.6 | |
| Confidence Interval |
(2-Sided) 95% -31.1 to 10.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Steady-state Trough Serum Concentration (Cmin) of Abatacept During Double-Blind Treatment |
|---|---|
| Description | |
| Time Frame | Day 701 of the main study; sub-study Days 1, 85, 169, 253 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed= number of participants randomized; n =randomized participants with measurement at given time point. For the Day 701 measure, one apparent outlier sample was deleted.. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study randomized to receive double-blind abatacept 10 mg/kg | All participants in the sub-study randomized to receive double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Main Study Day 701 (n=41, 36) |
22992.0
(9722.1)
|
21713.5
(9520.5)
|
| Sub-Study Day 1 (n=46, 41) |
22213.0
(9275.8)
|
23620.7
(9648.0)
|
| Sub-Study Day 85 (n=47, 43) |
24919.5
(14516.2)
|
11922.1
(5681.8)
|
| Sub-Study Day 169 (n=48, 43) |
25725.7
(18500.5)
|
9959.2
(5045.0)
|
| Sub-Study Day 253 (n=47, 42) |
28524.7
(19989.9)
|
13516.2
(6564.6)
|
| Title | Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations During Double-Blind Treatment |
|---|---|
| Description | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Related AE/SAE=Certain, Probable, Possible, or Missing. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. |
| Time Frame | From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed = All treated participants during the double-blind period. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study treated with double-blind abatacept 10 mg/kg | All participants in the sub-study treated with double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Deaths |
0
0%
|
2.0
4%
|
| SAEs |
5.2
9%
|
6.0
12%
|
| Related SAEs |
1.7
2.9%
|
0
0%
|
| Discontinued due to SAEs |
0
0%
|
2.0
4%
|
| AEs |
65.5
112.9%
|
50.0
100%
|
| Related AEs |
20.7
35.7%
|
10.0
20%
|
| Discontinued due to AEs |
0
0%
|
2.0
4%
|
| Title | Percentage of Participants With Infection and Infestation AEs Reported During Double-Blind Treatment |
|---|---|
| Description | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Infection and Infestation AEs = any AE within the System Organ Class Infection and Infestation. |
| Time Frame | From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed = All treated participants during the double-blind period. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study treated with double-blind abatacept 10 mg/kg | All participants in the sub-study treated with double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Total Participants with Infection and Infestation |
37.9
65.3%
|
26.0
52%
|
| Upper Respiratory Tract Infection |
5.2
9%
|
12.0
24%
|
| Nasopharyngitis |
5.2
9%
|
6.0
12%
|
| Influenza |
5.2
9%
|
4.0
8%
|
| Bronchitis |
5.2
9%
|
2.0
4%
|
| Urinary Tract Infection |
3.4
5.9%
|
4.0
8%
|
| Onychomycosis |
3.4
5.9%
|
2.0
4%
|
| Pharyngitis |
3.4
5.9%
|
2.0
4%
|
| Rhinitis |
3.4
5.9%
|
2.0
4%
|
| Ear Infection |
3.4
5.9%
|
0
0%
|
| Vaginal Infection |
3.4
5.9%
|
0
0%
|
| Appendicitis |
1.7
2.9%
|
0
0%
|
| Furuncle |
1.7
2.9%
|
0
0%
|
| Pneumonia |
1.7
2.9%
|
0
0%
|
| Sinusitis Bacterial |
1.7
2.9%
|
0
0%
|
| Endocarditis |
0
0%
|
2.0
4%
|
| Fungal Skin Infection |
0
0%
|
2.0
4%
|
| Herpes Simplex |
0
0%
|
2.0
4%
|
| Labyrinthitis |
0
0%
|
2.0
4%
|
| Oral Herpes |
0
0%
|
2.0
4%
|
| Respiratory Tract Infection |
0
0%
|
2.0
4%
|
| Sinusitis |
0
0%
|
2.0
4%
|
| Title | Percentage of Participants With Malignant Neoplasms Reported During Double-Blind Treatment |
|---|---|
| Description | All neoplasms were assessed by medical review as to whether or not the event was malignant. |
| Time Frame | From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed = All treated participants during the double-blind period. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study treated with double-blind abatacept 10 mg/kg | All participants in the sub-study treated with double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
| Title | Percentage of Participants With Prespecified Acute Infusional Adverse Events (AIAEs) During Double-Blind Treatment, by Intensity |
|---|---|
| Description | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Acute Infusional AE= a subset of the peri-infusional AEs with onset during the first hour after the start of the study drug infusion. A total of 105 infusional events were prespecified in the protocol. |
| Time Frame | From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed = All treated participants during the double-blind period. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study treated with double-blind abatacept 10 mg/kg | All participants in the sub-study treated with double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Total Participants with AIAEs (mild) |
0
0%
|
2.0
4%
|
| Total Participants with AIAEs (moderate) |
0
0%
|
0
0%
|
| Total Participants with AIAEs (severe) |
0
0%
|
0
0%
|
| Total Participants with AIAEs (very severe) |
0
0%
|
0
0%
|
| Vascular Disorders - Hypertension (mild) |
0
0%
|
2.0
4%
|
| Vascular Disorders - Hypertension (moderate) |
0
0%
|
0
0%
|
| Vascular Disorders - Hypertension (severe) |
0
0%
|
0
0%
|
| Vascular Disorders - Hypertension (very severe) |
0
0%
|
0
0%
|
| Vascular Disorders - Hypertension (unknown) |
0
0%
|
0
0%
|
| Title | Percentage of Participants With Prespecified Peri-Infusional Adverse Events (PAIAEs) During Double-Blind Treatment, by Intensity |
|---|---|
| Description | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Peri-infusional AE=a pre-specified infusional AE occuring during the first 24 hours after the start of study drug infusion.A total of 105 infusional events were prespecified in the protocol. GDASC=General Disorders and Administration Site Conditions, RTMD=Respiratory, Thoracic and Mediastinal Disorders. |
| Time Frame | From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed = All treated participants during the double-blind period. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study treated with double-blind abatacept 10 mg/kg | All participants in the sub-study treated with double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Total Participants with PIAEs (mild) |
6.9
11.9%
|
4.0
8%
|
| Total Participants with PIAEs (moderate) |
1.7
2.9%
|
0
0%
|
| Total Participants with PIAEs (severe) |
0
0%
|
0
0%
|
| Total Participants with PIAEs (very severe) |
0
0%
|
0
0%
|
| Gastrointestinal Disorders, Nausea (mild) |
1.7
2.9%
|
0
0%
|
| Gastrointestinal Disorders, Nausea (moderate) |
0
0%
|
0
0%
|
| Gastrointestinal Disorders, Nausea (severe) |
0
0%
|
0
0%
|
| Gastrointestinal Disorders, Nausea (very severe) |
0
0%
|
0
0%
|
| Gastrointestinal Disorders, Vomiting (mild) |
1.7
2.9%
|
0
0%
|
| Gastrointestinal Disorders, Vomiting (moderate) |
0
0%
|
0
0%
|
| Gastrointestinal Disorders, Vomiting (severe) |
0
0%
|
0
0%
|
| Gastrointestinal Disorders, Vomiting (very severe) |
0
0%
|
0
0%
|
| Nervous System Disorders, Dizziness (mild) |
1.7
2.9%
|
0
0%
|
| Nervous System Disorders, Dizziness (moderate) |
0
0%
|
0
0%
|
| Nervous System Disorders, Dizziness (severe) |
0
0%
|
0
0%
|
| Nervous System Disorders, Dizziness (very severe) |
0
0%
|
0
0%
|
| Nervous System Disorders, Headache (mild) |
0
0%
|
0
0%
|
| Nervous System Disorders, Headache (moderate) |
1.7
2.9%
|
0
0%
|
| Nervous System Disorders, Headache (severe) |
0
0%
|
0
0%
|
| Nervous System Disorders, Headache (very severe) |
0
0%
|
0
0%
|
| GDASC, Malaise (mild) |
1.7
2.9%
|
0
0%
|
| GDASC, Malaise (moderate) |
0
0%
|
0
0%
|
| GDASC, Malaise (severe) |
0
0%
|
0
0%
|
| GDASC, Malaise (very severe) |
0
0%
|
0
0%
|
| GDASC, Chest Pain (mild) |
0
0%
|
2.0
4%
|
| GDASC, Chest Pain (moderate) |
0
0%
|
0
0%
|
| GDASC, Chest Pain (severe) |
0
0%
|
0
0%
|
| GDASC, Chest Pain (very severe) |
0
0%
|
0
0%
|
| RTMD, Asthma (mild) |
1.7
2.9%
|
0
0%
|
| RTMD, Asthma (moderate) |
0
0%
|
0
0%
|
| RTMD, Asthma (severe) |
0
0%
|
0
0%
|
| RTMD, Asthma (very severe) |
0
0%
|
0
0%
|
| RTMD, Cough (mild) |
1.7
2.9%
|
0
0%
|
| RTMD, Cough (moderate) |
0
0%
|
0
0%
|
| RTMD, Cough (severe) |
0
0%
|
0
0%
|
| RTMD, Cough (very severe) |
0
0%
|
0
0%
|
| Vascular Disorders, Hypertension (mild) |
0
0%
|
2.0
4%
|
| Vascular Disorders, Hypertension (moderate) |
0
0%
|
0
0%
|
| Vascular Disorders, Hypertension (severe) |
0
0%
|
0
0%
|
| Vascular Disorders, Hypertension (very severe) |
0
0%
|
0
0%
|
| Title | Percentage of Participants With Pre-specified Autoimmune Disorders (ADs) Reported During Double-Blind Treatment, by Intensity |
|---|---|
| Description | A total of 127 autoimmune disorders were prespecified in the protocol. MCTD=Musculoskeletal and Connective Tissue Disorders |
| Time Frame | From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed = All treated participants during the double-blind period. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study treated with double-blind abatacept 10 mg/kg | All participants in the sub-study treated with double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Total Participants with ADs (mild) |
0
0%
|
4.0
8%
|
| Total Participants with ADs (moderate) |
0
0%
|
0
0%
|
| Total Participants with ADs (severe) |
0
0%
|
0
0%
|
| Total Participants with ADs (very severe) |
0
0%
|
0
0%
|
| Eye Disorders - Episcleritis (mild) |
0
0%
|
2.0
4%
|
| Eye Disorders - Episcleritis (moderate) |
0
0%
|
0
0%
|
| Eye Disorders - Episcleritis (severe) |
0
0%
|
0
0%
|
| Eye Disorders - Episcleritis (very severe) |
0
0%
|
0
0%
|
| MCTDs - Sjogren's Syndrome (mild) |
0
0%
|
2.0
4%
|
| MCTDs - Sjogren's Syndrome (moderate) |
0
0%
|
0
0%
|
| MCTDs - Sjogren's Syndrome (severe) |
0
0%
|
0
0%
|
| MCTDs - Sjogren's Syndrome (very severe) |
0
0%
|
0
0%
|
| Title | Percentage of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During Double-Blind Treatment |
|---|---|
| Description | Not evaluated: high hemoglobin,high hematocrit,high erythrocytes,high neutrophils+bands(N+B),low monocytes,low basophils,low eosinophils,low alkaline phosphatase(ALP),low aspartate aminotransferase(AST),low alanine aminotransferase(ALT),low G-Glutamyl transferase(GGT),low total bilirubin,low blood urea nitrogen,low creatinine,high albumin,low uric acid,low urine protein,low urine glucose,low urine blood,low urine leukocyte esterase,low urine white blood cells,low red blood cells.Pre Rx=pretreatment,(*)Lymphocytes(c/uL):Low<.750x10^3,High>7.50x10^3.(*)Eosinophils:>.750x10^3 c/uL. |
| Time Frame | From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed = All treated participants during the double-blind period; n=number of participants with specific measure |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study treated with double-blind abatacept 10 mg/kg | All participants in the sub-study treated with double-blind abatacept 5 mg/kg |
| Measure Participants | 58 | 50 |
| Hemoglobin, Low: >3 g/dL ↓ from pre rx (n=51, 48) |
0
0%
|
0
0%
|
| Hematocrit, Low: <0.75 x pre rx (n=51, 48) |
0
0%
|
0
0%
|
| Erythrocytes, Low: <0.75 x pre rx (n=51, 48) |
0
0%
|
0
0%
|
| ALP, High: >2 x upper limit normal (ULN)(n=52, 47) |
0
0%
|
0
0%
|
| Total Calcium, Low: <0.8 x Lower LN(LLN)(n=52, 47) |
0
0%
|
0
0%
|
| Platelet Count, Low: <0.67 x LLN (n=51, 48) |
0
0%
|
0
0%
|
| Platelet Count, High: >1.5 x ULN (n=51, 48) |
0
0%
|
0
0%
|
| Leukocytes, Low: <0.75 x LLN (n=51, 48) |
0
0%
|
0
0%
|
| N+B (absolute), Low: < 1.00 x 10^3 c/uL (n=55, 49) |
0
0%
|
0
0%
|
| Lymphocytes (absolute), Low (*) (n=55, 49) |
1.8
3.1%
|
2.0
4%
|
| Lymphocytes (absolute), High (*) (n=55, 49) |
0
0%
|
0
0%
|
| Monocytes (absolute), High: >2000/mm^3 (n=55, 49) |
0
0%
|
0
0%
|
| Basophils (absolute), High: > 400/mm^3 (n=55, 49) |
0
0%
|
0
0%
|
| Eosinophils (absolute), High (*) (n=55, 49) |
5.5
9.5%
|
2.0
4%
|
| AST, High: >3 x ULN (n=52, 47) |
0
0%
|
0
0%
|
| ALT, High: >3 x ULN (n=52, 47) |
0
0%
|
0
0%
|
| GGT, High: >2 x ULN (n=52, 47) |
0
0%
|
0
0%
|
| Bilirubin Total, High: >1.5 x ULN (n=52, 46) |
0
0%
|
0
0%
|
| Blood Urea Nitrogen, High: >2 x pre rx (n=52, 47) |
0
0%
|
0
0%
|
| Serum Sodium, Low: <0.95 x LLN (n=52, 47) |
0
0%
|
0
0%
|
| Serum Sodium, High: >1.05 x ULN, (n=52, 47) |
0
0%
|
0
0%
|
| Serum Potassium, Low: <0.9 x LLN (n=52, 47) |
0
0%
|
0
0%
|
| Serum Potassium, High: >1.1 x ULN (n=52, 47) |
0
0%
|
2.1
4.2%
|
| Serum Chloride, Low: <0.9 x LLN (n=52, 47) |
0
0%
|
0
0%
|
| Serum Chloride, High: >1.1 x ULN, (n=52, 47) |
0
0%
|
0
0%
|
| Total Calcium, High: >1.2 x ULN (n=52, 47) |
0
0%
|
0
0%
|
| Inorganic Phosphorus, Low: <0.75 x LLN (n=52, 47) |
0
0%
|
0
0%
|
| Inorganic Phosphorus, High: >1.25 x ULN (n=52, 47) |
0
0%
|
0
0%
|
| Serum Glucose, Low: <65 mg/dL (n=55, 48) |
5.5
9.5%
|
6.3
12.6%
|
| Serum Glucose, High: >220 mg/dL (n=55, 48) |
3.6
6.2%
|
4.2
8.4%
|
| Total Protein, Low: <0.9 x LLN (n=52, 47) |
0
0%
|
0
0%
|
| Total Protein, High: >1.1 x ULN (n=52, 47) |
0
0%
|
0
0%
|
| Albumin, Low: <0.9 x LLN (n=52, 47) |
0
0%
|
0
0%
|
| Uric Acid, High: >1.5 x ULN (n=52, 47) |
0
0%
|
0
0%
|
| Urine Protein, High: >=2-4 (n=55, 47) |
1.8
3.1%
|
6.4
12.8%
|
| Urine Glucose, High: >=2-4 (n=55, 47) |
5.5
9.5%
|
0
0%
|
| Urine Blood, High: >=2-4 (n=55, 47) |
12.7
21.9%
|
10.6
21.2%
|
| Urine Leukocyte Esterase, High: >=2-4 (n=20, 16) |
15.0
25.9%
|
25.0
50%
|
| Urine White Blood Cells, High: >=2-4 (n=22, 14) |
45.5
78.4%
|
14.3
28.6%
|
| Urine Red Blood Cells, High: >=2-4 (n=22, 14) |
22.7
39.1%
|
28.6
57.2%
|
| Title | Clinically Significant Changes in Vital Signs and Physical Findings |
|---|---|
| Description | Clinical significance was determined by investigator. Parameters include blood pressure, heart rate, respiration rate, and temperature. |
| Time Frame | From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis was not done because clinically significant changes in vital signs and physical findings were reported as adverse events. |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study treated with double-blind abatacept 10 mg/kg | All participants in the sub-study treated with double-blind abatacept 5 mg/kg |
| Measure Participants | 0 | 0 |
| Title | Participants With Positive Antibody Responses to Abatacept (Electrochemiluminescence [ECL] Method) During Double-Blind Treatment |
|---|---|
| Description | A positive antibody response to Abatacept (measured by the ECL assay) is further classified as a positive response for either Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Possibly immunoglobulin (Ig)' or 'Ig and/or Junction Region' |
| Time Frame | After 12 months of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed= Number of participants with available immunogenicity measurements |
| Arm/Group Title | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Arm/Group Description | All participants in the sub-study treated with double-blind abatacept 10 mg/kg | All participants in the sub-study treated with double-blind abatacept 5 mg/kg |
| Measure Participants | 56 | 49 |
| CTLA4 and Possibly IG |
4
6.9%
|
1
2%
|
| IG and/or Junction Region |
0
0%
|
1
2%
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Abatacept 5mg/kg (ST) | Abatacept 10mg/kg (ST) | Abatacept 10mg/kg (Open-Label) | |||
| Arm/Group Description | ||||||
All Cause Mortality |
||||||
| Abatacept 5mg/kg (ST) | Abatacept 10mg/kg (ST) | Abatacept 10mg/kg (Open-Label) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Abatacept 5mg/kg (ST) | Abatacept 10mg/kg (ST) | Abatacept 10mg/kg (Open-Label) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/50 (6%) | 3/58 (5.2%) | 2/8 (25%) | |||
| Blood and lymphatic system disorders | ||||||
| Leukopenia | 1/50 (2%) | 0/58 (0%) | 0/8 (0%) | |||
| Neutropenia | 1/50 (2%) | 0/58 (0%) | 0/8 (0%) | |||
| Cardiac disorders | ||||||
| Cardiopulmonary Failure | 1/50 (2%) | 0/58 (0%) | 0/8 (0%) | |||
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 0/50 (0%) | 0/58 (0%) | 1/8 (12.5%) | |||
| Infections and infestations | ||||||
| Appendicitis | 0/50 (0%) | 1/58 (1.7%) | 0/8 (0%) | |||
| Endocarditis | 1/50 (2%) | 0/58 (0%) | 0/8 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Diabetes Mellitus Inadequate Control | 1/50 (2%) | 0/58 (0%) | 0/8 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Acquired Claw Toe | 0/50 (0%) | 1/58 (1.7%) | 0/8 (0%) | |||
| Osteoarthritis | 1/50 (2%) | 0/58 (0%) | 1/8 (12.5%) | |||
| Rheumatoid Arthritis | 2/50 (4%) | 0/58 (0%) | 0/8 (0%) | |||
| Renal and urinary disorders | ||||||
| Renal Failure Acute | 1/50 (2%) | 0/58 (0%) | 0/8 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pleurisy | 0/50 (0%) | 1/58 (1.7%) | 0/8 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Abatacept 5mg/kg (ST) | Abatacept 10mg/kg (ST) | Abatacept 10mg/kg (Open-Label) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/50 (34%) | 18/58 (31%) | 7/8 (87.5%) | |||
| Eye disorders | ||||||
| Conjunctivitis | 2/50 (4%) | 0/58 (0%) | 1/8 (12.5%) | |||
| Xerophtalmia | 0/50 (0%) | 0/58 (0%) | 1/8 (12.5%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal Distension | 1/50 (2%) | 0/58 (0%) | 1/8 (12.5%) | |||
| Abdominal Pain Upper | 0/50 (0%) | 0/58 (0%) | 1/8 (12.5%) | |||
| Diarrhoea | 1/50 (2%) | 0/58 (0%) | 2/8 (25%) | |||
| Hiatus Hernia | 0/50 (0%) | 0/58 (0%) | 1/8 (12.5%) | |||
| Vomiting | 0/50 (0%) | 1/58 (1.7%) | 1/8 (12.5%) | |||
| General disorders | ||||||
| Fatigue | 3/50 (6%) | 0/58 (0%) | 0/8 (0%) | |||
| Infections and infestations | ||||||
| Bronchitis | 1/50 (2%) | 3/58 (5.2%) | 0/8 (0%) | |||
| Influenza | 2/50 (4%) | 3/58 (5.2%) | 0/8 (0%) | |||
| Nasopharyngitis | 3/50 (6%) | 3/58 (5.2%) | 1/8 (12.5%) | |||
| Upper Respiratory Tract Infection | 6/50 (12%) | 3/58 (5.2%) | 1/8 (12.5%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back Pain | 3/50 (6%) | 0/58 (0%) | 0/8 (0%) | |||
| Osteoarthritis | 0/50 (0%) | 1/58 (1.7%) | 1/8 (12.5%) | |||
| Nervous system disorders | ||||||
| Headache | 2/50 (4%) | 3/58 (5.2%) | 0/8 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Fibrocystic Breast Disease | 0/50 (0%) | 0/58 (0%) | 1/8 (12.5%) | |||
| Vascular disorders | ||||||
| Hypertension | 4/50 (8%) | 2/58 (3.4%) | 1/8 (12.5%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
| Name/Title | BMS Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00989235
Other Study ID Numbers:
- IM101-023 LT (Sub study)
- Eudrac # 2002-000784-26
First Posted:
Oct 5, 2009
Last Update Posted:
Jun 21, 2011
Last Verified:
Jun 1, 2011