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Trial record 1 of 1 for:    ra0028
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Magnetic Resonance Image Verified Early Response to Certolizumab Pegol in Subjects With Active Rheumatoid Arthritis (RA) (MARVELOUS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01235598
Recruitment Status : Completed
First Posted : November 5, 2010
Results First Posted : February 5, 2014
Last Update Posted : March 12, 2014
Sponsor:
Information provided by (Responsible Party):
UCB Pharma

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Other: Placebo
Biological: Certolizumab Pegol (CZP) 200 mg
Biological: Certolizumab Pegol (CZP) 400 mg
Enrollment 41
Recruitment Details The Participant Flow refers to the Randomized Set (RS) population which consists of all subjects randomized into the study.
Pre-assignment Details The study population consists of subjects with a diagnosis of adult-onset Rheumatoid Arthritis of at least 3 months duration but not longer than 15 years. In addition, subjects must be on Disease Modifying Anti-Rheumatic Drugs (DMARD) therapy for at least 12 weeks with a stable dose / route of administration for at least 8 weeks prior to Baseline.
Arm/Group Title Placebo Followed by Certolizumab Pegol (CZP) Certolizumab Pegol (CZP)
Hide Arm/Group Description Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40 Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Period Title: Overall Study
Started 13 28 [1]
Completed 12 24
Not Completed 1 4
Reason Not Completed
Adverse Event             0             3
Lack of Efficacy             0             1
Withdrawal by Subject             1             0
[1]
One subject was randomized to the CZP Arm but never received an injection (due to pre-treatment AE)
Arm/Group Title Placebo Followed by Certolizumab Pegol (CZP) Certolizumab Pegol (CZP) Total
Hide Arm/Group Description Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40 Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40 Total of all reporting groups
Overall Number of Baseline Participants 13 27 40
Hide Baseline Analysis Population Description
The Baseline characteristics refer to the Safety Set (SS) population. The Safety Population includes all subjects enrolled who received at least 1 injection of study treatment.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 27 participants 40 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
11
  84.6%
21
  77.8%
32
  80.0%
>=65 years
2
  15.4%
6
  22.2%
8
  20.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 27 participants 40 participants
48.3  (14.4) 51.3  (12.6) 50.4  (13.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 27 participants 40 participants
Female
10
  76.9%
22
  81.5%
32
  80.0%
Male
3
  23.1%
5
  18.5%
8
  20.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 27 participants 40 participants
Poland 2 7 9
Denmark 6 11 17
Netherlands 1 3 4
Sweden 4 6 10
1.Primary Outcome
Title Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 16 Compared to Baseline for Certolizumab Pegol Arm
Hide Description

Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS):

Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.

Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-1.0  (2.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Certolizumab Pegol (CZP)
Comments A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses. Hypotheses were ordered and tested in that order, beginning with change from Baseline at Week 16, and continuing to earlier time points (Week 8, 4, 2, 1 in that order) only if the previous null hypothesis of zero difference was rejected (p <0.05). Hypothesis testing was stopped if and when a non-significant result was obtained.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.049
Comments Two-sided p-value is presented, with p < 0.05 as the threshold for statistical significance.
Method Permutation test with general scores
Comments [Not Specified]
Method of Estimation Estimation Parameter Median difference within group changes
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-3.0 to 0.0
Estimation Comments Hodges-Lehmann estimate of median difference and associated exact 95 % 2-sided confidence interval are provided.
2.Primary Outcome
Title Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 8 Compared to Baseline for Certolizumab Pegol Arm
Hide Description

Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS):

Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.

Time Frame From Baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-0.7  (2.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Certolizumab Pegol (CZP)
Comments A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses. Hypotheses were ordered and tested in that order, beginning with change from Baseline at Week 16, and continuing to earlier time points (Week 8, 4, 2, 1 in that order) only if the previous null hypothesis of zero difference was rejected (p < 0.05). Hypothesis testing was stopped if and when a non-significant result was obtained. Testing was stopped in the next step.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.206
Comments Two-sided p-value is presented, with p < 0.05 as the threshold for statistical significance. A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses.
Method Permutation test with general scores
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference within group changes
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-3.0 to 1.0
Estimation Comments Hodges-Lehmann estimate of median difference and associated exact 95 % 2-sided confidence interval are provided.
3.Primary Outcome
Title Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 4 Compared to Baseline for Certolizumab Pegol Arm
Hide Description

Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS):

Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.

Time Frame From Baseline to Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-0.4  (1.6)
4.Primary Outcome
Title Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 2 Compared to Baseline for Certolizumab Pegol Arm
Hide Description

Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS):

Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.

Time Frame From Baseline to Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-0.4  (1.6)
5.Primary Outcome
Title Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 1 Compared to Baseline for Certolizumab Pegol Arm
Hide Description

Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS):

Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.

Time Frame From Baseline to Week 1
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-0.6  (1.8)
6.Secondary Outcome
Title Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Initiation Rate of Enhancement (IRE)
Hide Description

Contrast enhancement can be quantified in terms of the dynamic MRI parameters initial rate of enhancement (IRE), maximum enhancement (ME), and number of voxels (Nvox) with Plateau and Washout pattern. These parameters are extracted by examining individual signal intensity versus time curves derived from defined regions of interest.

Nvox indicates the number of voxels showing enhancement patterns. It is representative of the size or volume of enhancement and representative of underlying inflammation. The higher the value, the higher the volume .

ME and IRE values quantify the intensity of signal within the enhancing voxels. The absolute values and changes from Baseline in the MRI parameters of IRE, ME, and Nvox of the selected hand and wrist were estimated at Weeks 1, 2, 4, 8, and 16.

The values presented are for Proximal Interphalangeal (PIP) and Metacarpophalangeal (MCP) joints combined. A negative value in IRE change from Baseline score indicates an improvement.

Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: percent per second
-0.0044  (0.0140)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Certolizumab Pegol (CZP)
Comments A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses. Hypotheses were ordered and tested in that order, beginning with change from Baseline at Week 16, and continuing to earlier time points (Week 8, 4, 2, 1 in that order) only if the previous null hypothesis of zero difference was rejected (p <0.05). Hypothesis testing was stopped if and when a non-significant result was obtained.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments Two-sided p-value is presented, with p <0.05 as the threshold for statistical significance. A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses.
Method Permutation test with general scores
Comments [Not Specified]
Method of Estimation Estimation Parameter Median difference within group changes
Estimated Value -0.0035
Confidence Interval (2-Sided) 95%
-0.0120 to 0.0025
Estimation Comments Hodges-Lehmann estimate of median difference and associated exact 95 % 2-sided confidence interval are provided.
7.Secondary Outcome
Title Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Maximal Enhancement (ME)
Hide Description

Contrast enhancement can be quantified in terms of the dynamic MRI parameters initial rate of enhancement (IRE), maximum enhancement (ME), and number of voxels (Nvox) with Plateau and Washout pattern. These parameters are extracted by examining individual signal intensity versus time curves derived from defined regions of interest.

Nvox indicates the number of voxels showing enhancement patterns. It is representative of the size or volume of enhancement and representative of underlying inflammation. The higher the value, the higher the volume .

ME and IRE values quantify the intensity of signal within the enhancing voxels. The absolute values and changes from Baseline in the MRI parameters of IRE, ME, and Nvox of the selected hand and wrist were estimated at Weeks 1, 2, 4, 8, and 16.

The values presented are for Proximal Interphalangeal (PIP) and Metacarpophalangeal (MCP) joints combined. A negative value in ME change from Baseline score indicates an improvement.

Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: percent change over pre-contrast
-0.0172  (0.4459)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Certolizumab Pegol (CZP)
Comments A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses. Hypotheses were ordered and tested in that order, beginning with change from Baseline at Week 16, and continuing to earlier time points (Week 8, 4, 2, 1 in that order) only if the previous null hypothesis of zero difference was rejected (p <0.05). Hypothesis testing was stopped if and when a non-significant result was obtained.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.865
Comments Two-sided p-value is presented, with p <0.05 as the threshold for statistical significance. A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses.
Method Permutation test with general scores
Comments [Not Specified]
Method of Estimation Estimation Parameter Median difference within group changes
Estimated Value -0.0690
Confidence Interval (2-Sided) 95%
-0.2010 to 0.1380
Estimation Comments Hodges-Lehmann estimate of median difference and associated exact 95 % 2-sided confidence interval are provided.
8.Secondary Outcome
Title Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Number of Voxels (Nvox) With Plateau and Washout Pattern
Hide Description

Contrast enhancement can be quantified in terms of the dynamic MRI parameters initial rate of enhancement (IRE), maximum enhancement (ME), and number of voxels (Nvox) with Plateau and Washout pattern. These parameters are extracted by examining individual signal intensity versus time curves derived from defined regions of interest.

Nvox indicates the number of voxels showing enhancement patterns. It is representative of the size or volume of enhancement and representative of underlying inflammation. The higher the value, the higher the volume .

ME and IRE values quantify the intensity of signal within the enhancing voxels. The absolute values and changes from Baseline in the MRI parameters of IRE, ME, and Nvox of the selected hand and wrist were estimated at Weeks 1, 2, 4, 8, and 16.

The values presented are for Proximal Interphalangeal (PIP) and Metacarpophalangeal (MCP) joints combined. A negative value in Nvox change from Baseline score indicates an improvement.

Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: voxels
-813.3  (1457.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Certolizumab Pegol (CZP)
Comments A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses. Hypotheses were ordered and tested in that order, beginning with change from Baseline at Week 16, and continuing to earlier time points (Week 8, 4, 2, 1 in that order) only if the previous null hypothesis of zero difference was rejected (p <0.05). Hypothesis testing was stopped if and when a non-significant result was obtained.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments Two-sided p-value is presented, with p <0.05 as the threshold for statistical significance. A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses.
Method Permutation test with general scores
Comments [Not Specified]
Method of Estimation Estimation Parameter Median difference within group changes
Estimated Value -421.5
Confidence Interval (2-Sided) 95%
-1542.5 to -47.0
Estimation Comments Hodges-Lehmann estimate of median difference and associated exact 95 % 2-sided confidence interval are provided.
9.Secondary Outcome
Title Percentage of Subjects Achieving a Good European League Against Rheumatism (EULAR) Response at Week 16
Hide Description

EULAR (European League Against Rheumatism) response: EULAR response is based upon current Disease Activity Score 28 (DAS28) level and corresponding change from Baseline in DAS28.

Good EULAR response is defined as: DAS28 C-Reactive Protein (CRP) ≤ 3.2 and decrease from Baseline by > 1.2; moderate response is defined as achievement of one of the following:

  • DAS28(CRP) ≤ 3.2 and decrease from Baseline > 0.6 and ≤ 1.2
  • DAS28(CRP) > 3.2 and ≤ 5.1 and decrease from Baseline > 0.6
  • DAS28(CRP) > 5.1 and decrease from Baseline > 1.2
Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
Arm/Group Title Certolizumab Pegol (CZP) Placebo Followed by Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Overall Number of Participants Analyzed 21 12
Measure Type: Number
Unit of Measure: percentage of subjects
Good Response 71.4 66.7
Moderate Response 23.8 25.0
No Response 4.8 8.3
10.Secondary Outcome
Title Percentage of Subjects Meeting the American College of Rheumatology 20 % Criteria (ACR20) at Week 16
Hide Description Subjects who meet the ACR20 criteria are those subjects with at least 20 % improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-Reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).
Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
Arm/Group Title Certolizumab Pegol (CZP) Placebo Followed by Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Overall Number of Participants Analyzed 22 12
Measure Type: Number
Unit of Measure: percentage of subjects
Response 86.4 75.0
No Response 13.6 25.0
11.Secondary Outcome
Title Percentage of Subjects Meeting the American College of Rheumatology 50 % Criteria (ACR50) at Week 16
Hide Description Subjects who meet the ACR50 criteria are those subjects with at least 50 % improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-Reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).
Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
Arm/Group Title Certolizumab Pegol (CZP) Placebo Followed by Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Overall Number of Participants Analyzed 22 12
Measure Type: Number
Unit of Measure: percentage of subjects
Response 68.2 58.3
No Response 31.8 41.7
12.Secondary Outcome
Title Percentage of Subjects Meeting the American College of Rheumatology 70 % Criteria (ACR70) at Week 16
Hide Description Subjects who meet the ACR70 criteria are those subjects with at least 70 % improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-Reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).
Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
Arm/Group Title Certolizumab Pegol (CZP) Placebo Followed by Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Overall Number of Participants Analyzed 22 12
Measure Type: Number
Unit of Measure: percentage of subjects
Response 45.5 58.3
No Response 54.5 41.7
13.Secondary Outcome
Title Change From Baseline to Week 16 in the Disease Activity Score-28 (C-Reactive Protein) (DAS28 (CRP)) Response
Hide Description DAS28[CRP] is a composite index and is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) C-reactive protein (CRP in mg/l), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.36 x lognat (CRP+1) + 0.014 x Global Assessment of Arthritis + 0.96 where 28 joints are examined and a lower score indicates less disease activity. A DAS(28) score of higher than 5.1 is indicative of high disease activity whereas a DAS score below 3.2 indicates low disease activity. A patient is considered to be in remission if they have a DAS28 lower than 2.6. A negative value in DAS28[CRP] change from Baseline indicates an improvement from Baseline.
Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
Arm/Group Title Certolizumab Pegol (CZP) Placebo Followed by Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Overall Number of Participants Analyzed 21 12
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.27  (0.86) -2.50  (1.23)
14.Secondary Outcome
Title Percentage of Subjects Achieving Disease Activity Score 28 (DAS28 (CRP)) Remission Status (DAS28 (CRP) < 2.6) at Week 16
Hide Description DAS28[CRP] is a composite index and is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) C-reactive protein (CRP in mg/l), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.36 x lognat (CRP+1) + 0.014 x Global Assessment of Arthritis + 0.96 where 28 joints are examined and a lower score indicates less disease activity. A DAS(28) score of higher than 5.1 is indicative of high disease activity whereas a DAS score below 3.2 indicates low disease activity. A patient is considered to be in remission if they have a DAS28 lower than 2.6.
Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication, and had a valid Baseline efficacy assessment and at least one valid post-Baseline efficacy assessment.
Arm/Group Title Certolizumab Pegol (CZP) Placebo Followed by Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Overall Number of Participants Analyzed 21 12
Measure Type: Number
Unit of Measure: percentage of subjects
Remission 57.1 58.3
No Remission 42.9 41.7
15.Secondary Outcome
Title Change From Baseline to Week 16 in Bone Mineral Density as Measured by Digital XRay (DXR)
Hide Description

Radiographic assessment of bone mineral density in one hand and wrist were conducted by Digital X Ray (DXR) using a standardized imaging methodology. The hand and wrist to be assessed by DXR were the same as for the Magnetic Resonance Images (MRIs). The same hand and wrist were used for all x rays. The evaluation of all DXRs was performed centrally.

A positive value in Bone Mineral Density change from Baseline indicates an improvement.

Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
Arm/Group Title Certolizumab Pegol (CZP) Placebo Followed by Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Overall Number of Participants Analyzed 20 11
Mean (Standard Deviation)
Unit of Measure: g/cm^2
-0.00606  (0.01185) -0.00630  (0.01032)
16.Secondary Outcome
Title Change From Baseline to Week 16 in Tender Joint Count (TJC)
Hide Description The joint assessment was carried out on 28 joints. Swelling and tenderness were graded on a 2-point scale (answered with Yes/No). "No" indicated "Not tender"; "Yes" indicated a positive tenderness response that was defined as a positive response to questioning (tender), spontaneous response elicited (tender and winced) or withdrawal by subject on examination (tender, winced, and withdrew)." If there were missing observations in the TJC, then the remaining observations were assessed and weighted by dividing by the number of non-missing joint counts and multiplying by 28. TJC ranges from 0 to 28 with 0 indicating no tender joints and 28 indicating tenderness in all joints. A negative value in TJC change from Baseline indicates an improvement.
Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
Arm/Group Title Certolizumab Pegol (CZP) Placebo Followed by Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Overall Number of Participants Analyzed 23 12
Mean (Standard Deviation)
Unit of Measure: units on a scale
-9.28  (5.85) -9.92  (8.55)
17.Secondary Outcome
Title Change From Baseline to Week 16 in Swollen Joint Count (SJC)
Hide Description The joint assessment was carried out on 28 joints. Swelling and tenderness were graded on a 2-point scale (answered with Yes/No). "No" indicated "None" swelling response and "Yes" indicated that there was "a detectable synovial thickening with or without loss of bony contours, or bulging synovial proliferation with or without cystic characteristics." If there were missing observations in the SJC, then the remaining observations were assessed and weighted by dividing by the number of non-missing joint counts and multiplying by 28. SJC ranges from 0 to 28 with 0 indicating no swollen joints and 28 indicating swelling in all joints. A negative value in SJC change from Baseline indicates an improvement.
Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
Arm/Group Title Certolizumab Pegol (CZP) Placebo Followed by Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Overall Number of Participants Analyzed 23 12
Mean (Standard Deviation)
Unit of Measure: units on a scale
-7.06  (4.67) -7.92  (5.81)
18.Secondary Outcome
Title Change From Baseline to Week 16 in Health Assessment Questionnaire - Disability Index (HAQ-DI)
Hide Description The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a subject reported questionnaire that provides an assessment of the impact of the disease and its treatment on physical function. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question the level of difficulty is scored from 0 to 3 where 0 = no difficulty, 1 = some difficulty, 2 = much difficulty and 3 = unable to do. A total score is computed from the item scores using the scoring rules provided by the author (Fries, 1980). The total score ranges from 0 to 3 with lower scores meaning lower disability. A negative value in HAQ-DI change from Baseline indicates an improvement.
Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
Arm/Group Title Certolizumab Pegol (CZP) Placebo Followed by Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Overall Number of Participants Analyzed 23 12
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-0.54  (0.49) -0.79  (0.49)
19.Secondary Outcome
Title C-Reactive Protein (CRP) Ratio to Baseline at Week 16
Hide Description

The C-Reactive Protein (CRP) is considered a marker of inflammation in subjects with Rheumatoid Arthritis.

A ratio to Baseline < 1 indicates an improvement.

Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication, and had a valid Baseline efficacy assessment and at least one valid post-Baseline efficacy assessment.
Arm/Group Title Certolizumab Pegol (CZP) Placebo Followed by Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Overall Number of Participants Analyzed 21 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.491
(0.179% to 0.947%)
0.219
(147.9%)
20.Secondary Outcome
Title Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With European League Against Rheumatism (EULAR) Response at Week 16
Hide Description

EULAR (European League Against Rheumatism) response: EULAR response is based upon current Disease Activity Score 28 (DAS28) level and corresponding change from Baseline in DAS28.

Good EULAR response is defined as: DAS28 C-Reactive Protein (CRP) ≤ 3.2 and decrease from Baseline by > 1.2; moderate response is defined as achievement of one of the following:

  • DAS28(CRP) ≤ 3.2 and decrease from Baseline > 0.6 and ≤ 1.2
  • DAS28(CRP) > 3.2 and ≤ 5.1 and decrease from Baseline > 0.6
  • DAS28(CRP) > 5.1 and decrease from Baseline > 1.2

A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with better EULAR responses.

Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication. Correlations between the change from Baseline in total synovitis score at Week 16 and the clinical efficacy variables are restricted to the Certolizumab Pegol (CZP) arm only.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 20
Measure Type: Number
Unit of Measure: Spearman rank correlation coefficient
-0.20
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Certolizumab Pegol (CZP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.394
Comments [Not Specified]
Method Spearman rank correlation
Comments [Not Specified]
21.Secondary Outcome
Title Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 20 % Criteria (ACR20) at Week 16
Hide Description

Subjects who meet the ACR20 criteria are those subjects with at least 20 % improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-Reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).

A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with an ACR20 response at Week 16.

Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication. Correlations between the change from Baseline in total synovitis score at Week 16 and the clinical efficacy variables are restricted to the Certolizumab Pegol (CZP) arm only.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: Spearman rank correlation coefficient
-0.11
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Certolizumab Pegol (CZP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.625
Comments [Not Specified]
Method Spearman rank correlation
Comments [Not Specified]
22.Secondary Outcome
Title Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 50 % Criteria (ACR50) at Week 16
Hide Description

Subjects who meet the ACR50 criteria are those subjects with at least 50 % improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-Reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).

A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with an ACR50 response at Week 16.

Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication. Correlations between the change from Baseline in total synovitis score at Week 16 and the clinical efficacy variables are restricted to the Certolizumab Pegol (CZP) arm only.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: Spearman rank correlation coefficient
-0.34
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Certolizumab Pegol (CZP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.128
Comments [Not Specified]
Method Spearman rank correlation
Comments [Not Specified]
23.Secondary Outcome
Title Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 70 % Criteria (ACR70) at Week 16
Hide Description

Subjects who meet the ACR70 criteria are those subjects with at least 70 % improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-Reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).

A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with an ACR70 response at Week 16.

Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication. Correlations between the change from Baseline in total synovitis score at Week 16 and the clinical efficacy variables are restricted to the Certolizumab Pegol (CZP) arm only.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: Spearman rank correlation coefficient
-0.08
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Certolizumab Pegol (CZP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.732
Comments [Not Specified]
Method Spearman rank correlation
Comments [Not Specified]
24.Secondary Outcome
Title Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With Disease Activity Score-28 (DAS28 (CRP)) Response at Week 16
Hide Description

The DAS28(CRP) was calculated using the tender joint count (TJC) and swollen joint count (SJC), C-Reactive Protein (CRP in mg/L) and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm).

A positive correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with reductions in DAS28(CRP) at Week 16.

Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication. Correlations between the change from Baseline in total synovitis score at Week 16 and the clinical efficacy variables are restricted to the Certolizumab Pegol (CZP) arm only.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 20
Measure Type: Number
Unit of Measure: Spearman rank correlation coefficient
0.19
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Certolizumab Pegol (CZP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.411
Comments [Not Specified]
Method Spearman rank correlation
Comments [Not Specified]
25.Secondary Outcome
Title Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With Changes in Hand Bone Mineral Density as Measured by Digital XRay (DXR) at Week 16
Hide Description

Radiographic assessment of bone mineral density in one hand and wrist were conducted by Digital X Ray (DXR) using a standardized imaging methodology. The hand and wrist to be assessed by DXR were the same as for the Magnetic Resonance Images (MRIs). The same hand and wrist were used for all x rays. The evaluation of all DXRs was performed centrally.

A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with increases in bone mineral density at Week 16.

Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication. Correlations between the change from Baseline in total synovitis score at Week 16 and the clinical efficacy variables are restricted to the Certolizumab Pegol (CZP) arm only.
Arm/Group Title Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: Spearman rank correlation coefficient
0.32
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Certolizumab Pegol (CZP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.208
Comments [Not Specified]
Method Spearman rank correlation
Comments [Not Specified]
26.Secondary Outcome
Title Change From Baseline for the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Synovitis Score at Week 1 Placebo (PBO) Versus Certolizumab Pegol (CZP)
Hide Description

Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS):

Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions (the distal radioulnar; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment.

A negative value in synovitis change from Baseline score indicates an improvement.

Time Frame From Baseline to Week 1
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication, and had a valid Baseline efficacy assessment and at least one valid post-Baseline efficacy assessment.
Arm/Group Title Placebo Followed by Certolizumab Pegol (CZP) Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 13 27
Mean (Standard Deviation)
Unit of Measure: scores on a scale
0.1  (1.0) -0.6  (1.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Followed by Certolizumab Pegol (CZP), Certolizumab Pegol (CZP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.254
Comments Two-sided p-value is presented, with p <0.05 as the threshold for statistical significance.
Method Wilcoxon Rank-Sum Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.0 to 0.0
Estimation Comments Hodges-Lehmann estimate of median difference and associated exact 95 % 2-sided confidence interval are provided.
27.Secondary Outcome
Title Change From Baseline for the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Synovitis Score at Week 2 Placebo (PBO) Versus Certolizumab Pegol (CZP)
Hide Description

Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS):

Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions (the distal radioulnar; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment.

A negative value in synovitis change from Baseline score indicates an improvement.

Time Frame From Baseline to Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication, and had a valid Baseline efficacy assessment and at least one valid post-Baseline efficacy assessment.
Arm/Group Title Placebo Followed by Certolizumab Pegol (CZP) Certolizumab Pegol (CZP)
Hide Arm/Group Description:
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
Overall Number of Participants Analyzed 13 27
Mean (Standard Deviation)
Unit of Measure: scores on a scale
0.2  (1.4) -0.4  (1.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Followed by Certolizumab Pegol (CZP), Certolizumab Pegol (CZP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.472
Comments Two-sided p-value is presented, with p <0.05 as the threshold for statistical significance.
Method Wilcoxon Rank-Sum Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-2.0 to 1.0
Estimation Comments Hodges-Lehmann estimate of median difference and associated exact 95 % 2-sided confidence interval are provided.
Time Frame Treatment Emergent Adverse Events (TEAEs) were reported from Baseline (Week 0) to the end of the study (Week 50).
Adverse Event Reporting Description Subjects that did not receive at least one dose of Certolizumab Pegol (CZP) were excluded. Only Treatment Emergent Adverse Events (TEAEs) occurring while receiving CZP are reported.
 
Arm/Group Title Certolizumab Pegol (CZP) at Any Time
Hide Arm/Group Description

Eligible subjects were allocated to the following study treatments in a 2:1 ratio:

  • Certolizumab Pegol (CZP) 400mg for subcutaneous injection (sc) at Weeks 0, 2, and 4, followed by CZP 200mg sc and placebo (saline solution) at Week 6 and CZP 200mg at Weeks 8, 10, 12, 14, and 16 or
  • Placebo (saline solution) at Day 0 and then CZP 400mg sc at Weeks 2, 4, and 6 followed by CZP 200mg sc at Weeks 8, 10, 12, 14, and 16
All-Cause Mortality
Certolizumab Pegol (CZP) at Any Time
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Certolizumab Pegol (CZP) at Any Time
Affected / at Risk (%) # Events
Total   4/40 (10.00%)    
Cardiac disorders   
Splinter haemorrhages * 1  1/40 (2.50%)  1
Coronary artery disease * 1  1/40 (2.50%)  1
Injury, poisoning and procedural complications   
Post procedural haemorrhage * 1  1/40 (2.50%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Bladder transitional cell carcinoma stage I * 1  1/40 (2.50%)  1
Bladder cancer * 1  1/40 (2.50%)  1
Nervous system disorders   
Sensory Loss * 1  1/40 (2.50%)  1
Surgical and medical procedures   
Tonsillectomy * 1  1/40 (2.50%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Certolizumab Pegol (CZP) at Any Time
Affected / at Risk (%) # Events
Total   26/40 (65.00%)    
Gastrointestinal disorders   
Nausea * 1  2/40 (5.00%)  2
General disorders   
Injection site pain * 1  3/40 (7.50%)  5
Injection site discolouration * 1  2/40 (5.00%)  5
Nodule * 1  2/40 (5.00%)  5
Injection site swelling * 1  2/40 (5.00%)  3
Fatigue * 1  2/40 (5.00%)  2
Pyrexia * 1  2/40 (5.00%)  2
Infections and infestations   
Nasopharyngitis * 1  8/40 (20.00%)  8
Urinary tract infection * 1  5/40 (12.50%)  5
Oral herpes * 1  4/40 (10.00%)  9
Viral infection * 1  4/40 (10.00%)  5
Influenza * 1  3/40 (7.50%)  3
Pharyngitis bacterial * 1  2/40 (5.00%)  5
Abscess * 1  2/40 (5.00%)  2
Pneumonia * 1  2/40 (5.00%)  2
Investigations   
Alanine aminotransferase increased * 1  3/40 (7.50%)  3
Aspartate aminotransferase increased * 1  2/40 (5.00%)  2
Hepatic enzyme increased * 1  2/40 (5.00%)  2
Metabolism and nutrition disorders   
Hypercholesterolaemia * 1  2/40 (5.00%)  2
Musculoskeletal and connective tissue disorders   
Tendonitis * 1  2/40 (5.00%)  3
Tendon pain * 1  2/40 (5.00%)  2
Nervous system disorders   
Headache * 1  4/40 (10.00%)  14
Dizziness * 1  3/40 (7.50%)  4
Paraesthesia * 1  2/40 (5.00%)  2
Renal and urinary disorders   
Haematuria * 1  2/40 (5.00%)  2
Respiratory, thoracic and mediastinal disorders   
Oropharyngeal pain * 1  6/40 (15.00%)  6
Cough * 1  4/40 (10.00%)  4
Skin and subcutaneous tissue disorders   
Rash * 1  2/40 (5.00%)  2
Vascular disorders   
Hypertension * 1  3/40 (7.50%)  3
Hot flush * 1  2/40 (5.00%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.0
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: UCB Clinical Trials Call Center
Organization: UCB
Phone: +1 877 822 9493
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Responsible Party: UCB Pharma
ClinicalTrials.gov Identifier: NCT01235598    
Other Study ID Numbers: RA0028
2009-013758-33 ( EudraCT Number )
First Submitted: November 4, 2010
First Posted: November 5, 2010
Results First Submitted: September 26, 2013
Results First Posted: February 5, 2014
Last Update Posted: March 12, 2014