Magnetic Resonance Image Verified Early Response to Certolizumab Pegol in Subjects With Active Rheumatoid Arthritis (RA) (MARVELOUS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma
ClinicalTrials.gov Identifier:
NCT01235598
First received: November 4, 2010
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

Phase IIIb study to determine early response to Certolizumab Pegol (CZP) with Magnetic Resonance Imaging (MRI) score Outcome Measures in Rheumatoid Arthritis (RA) Clinical Trials (OMERACT) RA MRI Scoring System (RAMRIS) in subjects with RA.


Condition Intervention Phase
Rheumatoid Arthritis
Other: Placebo
Biological: Certolizumab Pegol (CZP) 200 mg
Biological: Certolizumab Pegol (CZP) 400 mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 16-week Double-blind, Placebo-controlled (for Initial 2 Weeks) Randomized Period, Followed by a 24-week Open-label Extension to Assess Magnetic Resonance Image (MRI) - Verified Early Response to Certolizumab Pegol in Subjects With Active Rheumatoid Arthritis (RA)

Resource links provided by NLM:


Further study details as provided by UCB Pharma:

Primary Outcome Measures:
  • 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 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

    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.


  • 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 [ Time Frame: From Baseline to Week 8 ] [ Designated as safety issue: No ]

    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.


  • 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 [ Time Frame: From Baseline to Week 4 ] [ Designated as safety issue: No ]

    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.


  • 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 [ Time Frame: From Baseline to Week 2 ] [ Designated as safety issue: No ]

    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.


  • 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 [ Time Frame: From Baseline to Week 1 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Initiation Rate of Enhancement (IRE) [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Maximal Enhancement (ME) [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Number of Voxels (Nvox) With Plateau and Washout Pattern [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

    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.


  • Percentage of Subjects Achieving a Good European League Against Rheumatism (EULAR) Response at Week 16 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

    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

  • Percentage of Subjects Meeting the American College of Rheumatology 20 % Criteria (ACR20) at Week 16 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]
    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).

  • Percentage of Subjects Meeting the American College of Rheumatology 50 % Criteria (ACR50) at Week 16 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]
    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).

  • Percentage of Subjects Meeting the American College of Rheumatology 70 % Criteria (ACR70) at Week 16 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline to Week 16 in the Disease Activity Score-28 (C-Reactive Protein) (DAS28 (CRP)) Response [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Subjects Achieving Disease Activity Score 28 (DAS28 (CRP)) Remission Status (DAS28 (CRP) < 2.6) at Week 16 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 16 in Bone Mineral Density as Measured by Digital XRay (DXR) [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline to Week 16 in Tender Joint Count (TJC) [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 16 in Swollen Joint Count (SJC) [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 16 in Health Assessment Questionnaire - Disability Index (HAQ-DI) [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.

  • C-Reactive Protein (CRP) Ratio to Baseline at Week 16 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

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

    A ratio to Baseline < 1 indicates an improvement.


  • Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With European League Against Rheumatism (EULAR) Response at Week 16 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

    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.


  • 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 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

    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.


  • 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 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

    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.


  • 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 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

    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.


  • 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 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

    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.


  • 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 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]

    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.


  • 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) [ Time Frame: From Baseline to Week 1 ] [ Designated as safety issue: No ]

    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.


  • 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) [ Time Frame: From Baseline to Week 2 ] [ Designated as safety issue: No ]

    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.



Enrollment: 41
Study Start Date: December 2010
Study Completion Date: May 2013
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo followed by Certolizumab Pegol (CZP)
Placebo, saline solution for sc 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
Other: Placebo
Placebo provided for the first subcutaneous injection in single-use vials at Week 0 (2 vials required), then Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4 and 6, followed by Certolizumab Pegol (CZP) 200 mg every 2 weeks from Week 8 to Week 40
Other Name: PBO
Biological: Certolizumab Pegol (CZP) 200 mg
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
Other Names:
  • Cimzia®
  • CZP
  • CDP870
Biological: Certolizumab Pegol (CZP) 400 mg
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
Other Names:
  • Cimzia®
  • CZP
  • CDP870
Experimental: Certolizumab Pegol (CZP)
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
Biological: Certolizumab Pegol (CZP) 200 mg
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
Other Names:
  • Cimzia®
  • CZP
  • CDP870
Biological: Certolizumab Pegol (CZP) 400 mg
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
Other Names:
  • Cimzia®
  • CZP
  • CDP870

Detailed Description:

To identify the efficacy of Certolizumab Pegol (CZP) on synovitis in dynamic MRI parameters; to make the correlation between European League Against Rheumatism (EULAR), American College of Rheumatology (ACR)p, Disease Activity Score-28 (DAS 28) responses, and Digital XRay (DXR) assessment with reduction of synovitis.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with a diagnosis of adult-onset Rheumatoid Arthritis (RA) of at least 3 months duration but no longer than 15 years
  • Subjects with an active adult Rheumatoid Arthritis disease
  • Subjects who have been on Disease-Modifying Anti-Rheumatic Drug (DMARD) therapy for at least 12 weeks

Exclusion Criteria:

  • Subject must not have a secondary, non-inflammatory type of musculoskeletal condition (eg, osteoarthritis or fibromyalgia) that in the investigator's opinion is symptomatic enough to interfere with evaluation of the effect of study drug on the subject's primary diagnosis of Rheumatoid Arthritis (RA)
  • Subject must not have a diagnosis of any other inflammatory arthritis (eg, psoriatic arthritis or ankylosing spondylitis)
  • Subject must not have a history of an infected joint prosthesis at any time with prosthesis still in situ
  • Subject must not have received more than 1 biological agent
  • Subject must not have a history of lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease at any time
  • Subject with known Tuberculosis (TB) disease, high risk of acquiring TB infection or latent TB infection
  • Subject must not have a known hypersensitivity to any components of the investigational medicinal product
  • Subject must not have contraindications for Magnetic Resonance Image (MRI) and contrast agent
  • Subject must not have any other condition which, in the investigator's judgement, would make them unsuitable for inclusion in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01235598

Locations
Denmark
003
Frederiksberg, Denmark
002
Hellerup, Denmark
001
Hvidovre, Denmark
016
Slagelse, Denmark
Netherlands
012
Nijmegen, Netherlands
010
Utrecht, Netherlands
Poland
018
Warszawa, Poland
019
Warszawa, Poland
Sweden
008
Goteburg, Sweden
004
Malmoe, Sweden
Sponsors and Collaborators
UCB Pharma
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

Additional Information:
No publications provided

Responsible Party: UCB Pharma
ClinicalTrials.gov Identifier: NCT01235598     History of Changes
Other Study ID Numbers: RA0028, 2009-013758-33
Study First Received: November 4, 2010
Results First Received: September 26, 2013
Last Updated: February 7, 2014
Health Authority: Sweden: Medical Products Agency
Denmark: Danish Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by UCB Pharma:
Cimzia®
CDP870
CZP
Certolizumab Pegol
Rheumatoid Arthritis
MRI

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Certolizumab pegol
Immunoglobulin Fab Fragments
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014