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Trial record 3 of 9 for:    "Synovitis" | "Folate"

A Rheumatoid Arthritis Study to Assess Early Response to Abatacept+MTX as Defined by Improvement of Synovitis Measures by Power Doppler Ultrasonography

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ClinicalTrials.gov Identifier: NCT00767325
Recruitment Status : Completed
First Posted : October 7, 2008
Results First Posted : June 21, 2013
Last Update Posted : July 2, 2013
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Rheumatoid Arthritis
Interventions Drug: Abatacept
Drug: Methotrexate
Enrollment 104
Recruitment Details  
Pre-assignment Details A total of 164 participants were screened; 104 were enrolled in the study and received open-label treatment with abatacept.
Arm/Group Title Abatacept, 10 mg/kg
Hide Arm/Group Description All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Period Title: Overall Study
Started 104
Completed 89
Not Completed 15
Reason Not Completed
Lack of Efficacy             2
Adverse Event             7
Lost to Follow-up             3
No longer met study criteria             2
Missed visit due to family reasons             1
Arm/Group Title Abatacept, 10 mg/kg
Hide Arm/Group Description All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Overall Number of Baseline Participants 104
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 104 participants
56.4  (14.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants
Female
87
  83.7%
Male
17
  16.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 104 participants
American Indian or Alaska Native 1
Asian 1
Native Hawaiian or Other Pacific Islander 0
Black or African American 0
White 101
Other 1
Tender joint count  
Mean (Standard Deviation)
Unit of measure:  Joints
Number Analyzed 104 participants
19.5  (12.5)
Duration of rheumatoid arthritis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 104 participants
7.3  (9.1)
Swollen joint count  
Mean (Standard Deviation)
Unit of measure:  Joints
Number Analyzed 104 participants
13.0  (7.6)
DAS 28-CRP score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 104 participants
5.2888  (1.105)
[1]
Measure Description: DAS28-CRP=Disease Activity Score 28 using C-Reactive Protein. The DAS28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient’s global assessment of health (ranging from very good to very bad). These measures are then fed into a complex mathematical formula to produce the overall DAS (greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
Global PDUS (MCP 2-5) score (n=96)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 104 participants
12.6  (4.1)
[1]
Measure Description: Power Doppler ultrasonography (PDUS) assessed synovial inflammation of metacarpophalangeal (MCP) joints (2-5) in both hands. Total PDUS score=sum of joints measured. Grade (Gr) 0, or normal=normal joint (no synovial hypertrophy(SH), no Doppler signal [[DS]); Gr 1 or minimal (min)=min synovitis (min SH with ≤Gr 1 Gr 2 or no DS); moderate (mod)=mod synovitis (mod SH with ≤Gr 2 Doppler signal or min SH and Gr 2 DS); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 DS or min or mod SH and Gr 3 DS). Total possible score range: 8 to 24 (8*1, 8*3) for 2 hands. Higher grade=more severe disease.
1.Primary Outcome
Title Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis)
Hide Description LOCF=last observation carried forward. PDUS assessed the degree of synovial inflammation of the MCP joints (2nd to 5th) of both hands and was performed at approximately the same time of day for each participant. Total PDUS scores are independent of the presence and grade of joint effusion and are evaluated as follows: Grade 0 or normal=normal joint (no synovial hypertrophy, no Doppler signal); Grade 1 or minimal=minimal synovitis (minimal synovial hypertrophy, with ≤Grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate synovial hypertrophy with ≤Grade 2 Doppler signal or minimal synovial hypertrophy and Grade 2 Doppler signal; Grade 3 or severe=severe synovitis (severe synovial hypertrophy with ≤Grade 3 Doppler signal or minimal or moderate synovial hypertrophy and Grade 3 Doppler signal). Each joint is rated 1 to 3, for a total possible score ranging from 8 to 24 (8*1, 8*3) for 2 hands. Higher grade/score=more severe disease. Change=score Day x - baseline score.
Time Frame Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 infusion of study drug and who had baseline and at least 1 postbaseline efficacy measurements available. Excludes 8 participants with PDUS values from 1 site that experienced technical and quality issues with PDUS scoring and compliance.
Arm/Group Title Abatacept, 10 mg/kg
Hide Arm/Group Description:
All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Overall Number of Participants Analyzed 96
Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
Day 7 (n=86)
-0.7
(-1.2 to -0.1)
Day 15 (n=94)
-1.3
(-2.0 to -0.7)
Day 29 (n=95)
-2.4
(-3.2 to -1.7)
Day 43 (n=95)
-2.9
(-3.7 to -2.1)
Day 57 (n=95)
-3.2
(-4.0 to -2.4)
Day 85 (n=95)
-3.8
(-4.7 to -2.9)
Day 113 (n=95)
-4.5
(-5.4 to -3.5)
Day 141 (n=95)
-4.8
(-5.8 to -3.8)
Day 169 (n=95)
-4.8
(-5.8 to -3.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept, 10 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.2 to -0.1
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.282
Estimation Comments Day 7
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Abatacept, 10 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-2.0 to -0.7
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.308
Estimation Comments Day 15
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Abatacept, 10 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-3.2 to -1.7
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.383
Estimation Comments Day 29
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Abatacept, 10 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.9
Confidence Interval (2-Sided) 95%
-3.7 to -2.1
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.384
Estimation Comments Day 43
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Abatacept, 10 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-4.0 to -2.4
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.393
Estimation Comments Day 57
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Abatacept, 10 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.8
Confidence Interval (2-Sided) 95%
-4.7 to -2.9
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.454
Estimation Comments Day 85
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Abatacept, 10 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.5
Confidence Interval (2-Sided) 95%
-5.4 to -3.5
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.472
Estimation Comments Day 113
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Abatacept, 10 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-5.8 to -3.8
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.492
Estimation Comments Day 141
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Abatacept, 10 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-5.8 to -3.9
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.473
Estimation Comments Day 169
2.Primary Outcome
Title Earliest Time Point at Which Improvement of Core Component of the Global PDUS in the MCP (2-5) Joints of Both Hands Was Assessed
Hide Description MCP=metacarpophalangeal; PDUS=power Doppler ultrasonography. Time point at which early signs of Global PDUS improvement were observed=earliest time point for which 0 was not included in the 95% confidence interval for the mean changes from baseline in Global PDUS (MCP 2-5) score at that and all later time points. Total PDUS scores are independent of the presence and grade of joint effusion: Grade (Gr) 0 or normal=normal joint (no synovial hypertrophy [SH], no Doppler signal); Gr 1 or minimal=minimal synovitis (minimal SH, with ≤Gr 1 Doppler signal); Gr 2 or moderate=moderate synovitis (moderate SH, with ≤Gr 2 Doppler signal or minimal SH and grade 2 Doppler signal); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 Doppler signal or minimal or moderate SH and Gr 3 Doppler signal). Each joint is rated 1 to 3, for a total possible score ranging from 8 to 24 (8*1, 8*3) for the 2 hands. Higher Gr/score=more severe disease.
Time Frame Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 infusion of study drug and who had baseline and at least 1 postbaseline efficacy measurements available. Excludes 8 participants with PDUS values from 1 site that experienced technical and quality issues with PDUS scoring and compliance.
Arm/Group Title Abatacept, 10 mg/kg
Hide Arm/Group Description:
All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Overall Number of Participants Analyzed 96
Measure Type: Number
Unit of Measure: Day
7
3.Secondary Outcome
Title Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis)
Hide Description PDUS=power Doppler ultrasonography; MCP=metacarpophalangeal; LOCF=last observation carried forward. PDUS was used to assess the degree of synovial inflammation of the MCP joints (2nd to 5th) of both hands and was performed at approximately the same time of day for each participant. PDUS scores are independent of the presence and grade of joint effusion and are evaluated as follows: Grade 0 or normal=normal joint (no synovial hypertrophy, no Doppler signal); Grade 1 or minimal=minimal synovitis (minimal synovial hypertrophy, with ≤Grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate synovial hypertrophy with ≤Grade 2 Doppler signal or minimal synovial hypertrophy and grade 2 Doppler signal); Grade 3 or severe=severe synovitis (severe synovial hypertrophy with ≤ Grade 3 Doppler signal or minimal or 1-3, for a total possible score ranging from 8 to 24 (8*1, 8*3) for the 2 hands. Higher grade/score=more severe disease. Change=score Day X-baseline score.
Time Frame Days 7, 15, 29, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 infusion of study drug and who had baseline and at least 1 postbaseline efficacy measurements available. Excludes 8 participants with PDUS values from 1 site that experienced technical and quality issues with PDUS scoring and compliance.
Arm/Group Title Abatacept, 10 mg/kg
Hide Arm/Group Description:
All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Overall Number of Participants Analyzed 96
Mean (Standard Error)
Unit of Measure: Units on a scale
Synovial hypertrophy (n=86): Day 7 -0.6  (0.297)
Synovial hypertrophy (n=94): Day 15 -1.0  (0.306)
Synovial hypertrophy (n=95): Day 29 -2.1  (0.377)
Synovial hypertrophy (n=95): Day 169 -4.5  (0.449)
Doppler signal: Day 7 (n=86) -0.9  (0.305)
Doppler signal: Day 15 (n=94) -1.9  (0.296)
Doppler signal: Day 29 (n=95) -2.2  (0.350)
Doppler signal: Day 169 (n=95) -4.8  (0.457)
Joint effusion: Day 7 (n=86) 0.1  (0.237)
Joint effusion: Day 15 (n=94) 0.1  (0.243)
Joint effusion: Day 29 (n=95) -0.8  (0.294)
Joint effusion: Day 169 (n=95) -1.9  (0.351)
4.Secondary Outcome
Title Number of Early (Days 7 to 113) Global PDUS MCP 2-5 Scores or Global PDUS Component MCP 2-5 Scores Associated With an Acceptable Predictability of Clinical Response at Day 169, As Assessed by DAS28-CRP
Hide Description MCP=metacarpophalangeal; PDUS=power Doppler ultrasonography; DAS=Disease Activity Score;CRP=C-reactive protein. Receiver Operator Characteristics (ROC) analysis assessed predicatability. ROC curve analyses performed; area under the curve of ≥0.7 was considered acceptable for prediction. Clinical response defined as: Clinically Meaningful Improvement=drop from baseline of ≥1.2 in DAS28-CRP; Remission=DAS28-CRP score <2.6; Low Disease Activity=≤3.2. PDUS scores: Grade (Gr) 0 or normal=normal joint (no synovial hypertrophy [SH], no Doppler signal); Gr 1 or minimal=minimal synovitis (minimal SH, with ≤Gr 1 Doppler signal); Gr 2 or moderate=moderate synovitis (moderate SH with ≤Gr 2 Doppler signal or minimal SH and Gr 2 Doppler signal); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 Doppler signal or minimal or moderate SH and Gr 3 Doppler signal). Each joint rated 1-3, for a total possible score ranging from 8-24 (8*1, 8*3)for the 2 hands. Higher gr/score=more severe disease.
Time Frame Days 1 to 169
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 infusion of study drug and who had baseline and at least 1 postbaseline efficacy measurements available. Excludes 8 participants with PDUS values from 1 site that experienced technical and quality issues with PDUS scoring and compliance.
Arm/Group Title Abatacept, 10 mg/kg
Hide Arm/Group Description:
All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Overall Number of Participants Analyzed 96
Measure Type: Number
Unit of Measure: Scores
Clinically meaningful improvement 0
Remission 0
Low disease activity 0
5.Secondary Outcome
Title Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.
Time Frame Days 1 to 169 to 56 days following last infusion
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 infusion of study drug.
Arm/Group Title Abatacept, 10 mg/kg
Hide Arm/Group Description:
All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Overall Number of Participants Analyzed 104
Measure Type: Number
Unit of Measure: Participants
Deaths 0
SAEs 6
Treatment-related SAEs 2
Discontinuations due to SAEs 1
AEs 62
Treatment-related AEs 22
Discontinuations due to AEs 6
6.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) of Interest
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Infusion reaction: acute=1 hour or less after start of dosing; periinfusional=24 hours or less after start of dosing.
Time Frame Days 1 to 169 to 56 days following last infusion
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 infusion of study drug.
Arm/Group Title Abatacept, 10 mg/kg
Hide Arm/Group Description:
All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Overall Number of Participants Analyzed 104
Measure Type: Number
Unit of Measure: Participants
Infections 20
Malignancy 1
Autoimmune disorders (prespecified) 2
Infusion reactions (prespecified): Acute 4
Infusion reactions (prespecified): Periinfusional 10
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Aba 10 mg/kg
Hide Arm/Group Description [Not Specified]
All-Cause Mortality
Aba 10 mg/kg
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Aba 10 mg/kg
Affected / at Risk (%)
Total   6/104 (5.77%) 
Cardiac disorders   
Atrial fibrillation  1  1/104 (0.96%) 
Infections and infestations   
Bursitis infective  1  1/104 (0.96%) 
Nervous system disorders   
Dementia  1  1/104 (0.96%) 
Reproductive system and breast disorders   
Endometriosis  1  1/104 (0.96%) 
Respiratory, thoracic and mediastinal disorders   
Pulmonary fistula  1  1/104 (0.96%) 
Pleural effusion  1  1/104 (0.96%) 
Vascular disorders   
Hypertension  1  1/104 (0.96%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Aba 10 mg/kg
Affected / at Risk (%)
Total   15/104 (14.42%) 
Infections and infestations   
Nasopharyngitis  1  7/104 (6.73%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  9/104 (8.65%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Power Doppler ultrasonography values from 1 site (8 participants were excluded due to technical and quality issues with PDUS scoring and compliance issues.)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00767325     History of Changes
Other Study ID Numbers: IM101-179
First Submitted: October 6, 2008
First Posted: October 7, 2008
Results First Submitted: March 13, 2013
Results First Posted: June 21, 2013
Last Update Posted: July 2, 2013