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A Study to Evaluate the Effectiveness of Infliximab and Changes in Hand and Wrist Magnetic Resonance Imaging (MRI) in Participants With Active Rheumatoid Arthritis (RA) (P08136)

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ClinicalTrials.gov Identifier: NCT01313520
Recruitment Status : Completed
First Posted : March 11, 2011
Results First Posted : July 8, 2013
Last Update Posted : May 10, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Arthritis, Rheumatoid
Interventions Drug: Infliximab
Drug: Placebo
Enrollment 61
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description 3 mg/kg of Infliximab intravenous infusion saline via intravenous infusion
Period Title: Overall Study
Started 30 31
Completed 30 31
Not Completed 0 0
Arm/Group Title Infliximab Placebo Total
Hide Arm/Group Description 3 mg/kg of Infliximab intravenous infusion saline via intravenous infusion Total of all reporting groups
Overall Number of Baseline Participants 30 31 61
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants 31 participants 61 participants
50.3  (9.5) 50.1  (10.7) 50.2  (10.04)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 31 participants 61 participants
Female
28
  93.3%
28
  90.3%
56
  91.8%
Male
2
   6.7%
3
   9.7%
5
   8.2%
1.Primary Outcome
Title Change From Baseline in the Volume Transfer Rate From the Blood Plasma to the Enhancing Synovium (Ktrans)
Hide Description Dynamic Contrast Enhanced (DCE) Magnetic Resonance Imaging (MRI) was performed on one hand at baseline, and then at treatment week 14 to measure the rate constant of transfer of contrast (Ktrans).
Time Frame Baseline and week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated with infliximab or placebo
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
3 mg/kg of Infliximab intravenous infusion
saline via intravenous infusion
Overall Number of Participants Analyzed 30 31
Least Squares Mean (95% Confidence Interval)
Unit of Measure: min ^-1
-0.2
(-0.3 to -0.1)
0.1
(-0.0 to 0.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Infliximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.4 to -0.1
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Responders With a 20% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR20).
Hide Description ACR20 requires that both tender and swollen joint counts improve by at least 20% from baseline, as well as a 20% improvement in at least 3 other core measures from the following: pain, patient's and physician's global assessment, physical disability and C-reactive protein (CRP).
Time Frame Baseline and week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated with Infliximab or Placebo
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
3 mg/kg of Infliximab intravenous infusion
saline via intravenous infusion
Overall Number of Participants Analyzed 30 31
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of responders
56.7
(41.9 to 70.4)
32.3
(20.3 to 47.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Infliximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Responders With a 50% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR50).
Hide Description ACR50 requires that both tender and swollen joint counts improve by at least 50% from baseline, as well as a 50% improvement in at least 3 other core measures from the following: pain, patient's and physician's global assessment, physical disability and CRP.
Time Frame Baseline and week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated with Infliximab or placebo
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
3 mg/kg of Infliximab intravenous infusion
saline via intravenous infusion
Overall Number of Participants Analyzed 30 31
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of responders
20.0
(10.7 to 34.2)
0
(0 to 0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Infliximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Standardized Z-scores of Composite Endpoint Consisting of Clinical Disease Activity Measure DAS28 CRP + Ktrans.
Hide Description Clinical disease activity score (DAS28 CRP) is a composite index of the following: number of tender joints (28 joint count), number of swollen joints (28 joint count), Patient Global Assessment of Disease Status (GADP) on a 100 mm visual analog scale (VAS) and concentration of CRP. Ktrans is the volume transfer rate from the blood plasma to the enhancing synovium. The individual endpoints are standardized using z-scores, then the z-scores are averaged to create a composite endpoint by use of O'Brien's global statistic.
Time Frame Baseline and Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated with Infliximab or placebo
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
3 mg/kg of Infliximab intravenous infusion
saline via intravenous infusion
Overall Number of Participants Analyzed 30 31
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Z-score
-0.8
(-1.3 to -0.3)
0.8
(0.3 to 1.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Infliximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect Size
Estimated Value 1.40
Confidence Interval (2-Sided) 90%
0.92 to 1.87
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Standardized Z-scores of Composite Endpoint Consisting of Clinical Disease Activity Measure DAS28 CRP + Rheumatoid Arthritis MRI Score (RAMRIS) Synovitis + RAMRIS Osteitis.
Hide Description

DAS28 CRP is a composite index of the following: number of tender joints (28 joint count), number of swollen joints (28 joint count), GADP on a 100 mm VAS and concentration of CRP. RAMRIS Synovitis is an ordinal scoring system of hand synovitis that is scored from 0 to 3 in 8 locations, ranging from 0 to 24 total. RAMRIS Osteitis is an ordinal scoring system of hand osteitis that is scored from 0 to 3 in 25 locations, ranging from 0 to 75 total. The individual

endpoints are standardized using z-scores, then the z-scores are averaged to create a composite endpoint by use of O'Brien's global statistic.

Time Frame Baseline and Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated with Infliximab or placebo
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
3 mg/kg of Infliximab intravenous infusion
saline via intravenous infusion
Overall Number of Participants Analyzed 30 31
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Z-score
-0.7
(-1.3 to -0.2)
0.8
(0.2 to 1.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Infliximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect Size
Estimated Value 1.10
Confidence Interval (2-Sided) 90%
0.64 to 1.55
Estimation Comments [Not Specified]
6.Other Pre-specified Outcome
Title Change From Baseline in DAS28 CRP.
Hide Description DAS28 CRP is a composite index of the following: number of tender joints (28 joint count), number of swollen joints (28 joint count), GADP on a 100 mm VAS and concentration of serum CRP. Scores can range from 2-10; with higher values corresponding to higher disease activity, and lower values to better outcomes.
Time Frame Baseline and Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated with infliximab or placebo
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
3 mg/kg of Infliximab via intravenous infusion
saline via intravenous infusion
Overall Number of Participants Analyzed 30 31
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-1.8
(-2.2 to -1.5)
-0.8
(-1.2 to -0.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Infliximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments [Not Specified]
7.Other Pre-specified Outcome
Title Change From Baseline in RAMRIS Synovitis.
Hide Description RAMRIS Synovitis is an ordinal scoring system of hand synovitis that is scored from 0 to 3 in 8 locations. The scores can range from 0 to 24, with higher values corresponding to higher disease activity, and lower values to better outcomes.
Time Frame Baseline and Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated with infliximab or placebo
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
3 mg/kg of Infliximab via intravenous infusion
saline via intravenous infusion
Overall Number of Participants Analyzed 30 31
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.30  (4.25) 0.24  (1.98)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Infliximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method van Elteren test
Comments [Not Specified]
8.Other Pre-specified Outcome
Title Change From Baseline in RAMRIS Osteitis.
Hide Description RAMRIS Osteitis is an ordinal scoring system of hand osteitis that is scored from 0 to 3 in 25 locations. The scores can range from 0 to 75, with higher values corresponding to higher disease activity, and lower values to better outcomes.
Time Frame Baseline and Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Participants treated with infliximab or placebo. One participant in the placebo group missing a baseline value was not included in the analysis.
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
3 mg/kg of Infliximab via intravenous infusion
Saline via intravenous infusion
Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
-3.10  (5.04) 0.48  (3.22)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Infliximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method van Elteren test
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description 3 mg/kg of Infliximab intravenous infusion saline via intravenous infusion
All-Cause Mortality
Infliximab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Infliximab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/30 (0.00%)      0/31 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Infliximab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/30 (26.67%)      8/31 (25.81%)    
Cardiac disorders     
Palpitations  2/30 (6.67%)  2 0/31 (0.00%)  0
Gastrointestinal disorders     
Abdominal Pain  0/30 (0.00%)  0 2/31 (6.45%)  2
Musculoskeletal and connective tissue disorders     
Joint Swelling  4/30 (13.33%)  4 6/31 (19.35%)  6
Nervous system disorders     
Headache  2/30 (6.67%)  2 0/31 (0.00%)  0
1
Term from vocabulary, MedDRA 15.1
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.
The investigator agrees not to publish or publicly present any interim results of the trial without the prior written consent of the sponsor. The investigator further agrees to provide to sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor has the right to review and comment on publications, abstracts, slides and manuscripts and on the data analysis and presentation.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp.
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01313520    
Other Study ID Numbers: P08136
2011-000079-14 ( EudraCT Number )
First Submitted: February 25, 2011
First Posted: March 11, 2011
Results First Submitted: February 12, 2013
Results First Posted: July 8, 2013
Last Update Posted: May 10, 2017