Back to resultsA Study to Evaluate the Safety and Efficacy of MabThera (Rituximab) in Combination With Methotrexate (MTX) in Participants With Active Rheumatoid Arthritis Who Failed on Anti-Tumor Necrosis Factor Alpha Therapy
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
MabThera/Rituxan
Methotrexate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Adult participants 18-80 years of age with active RA for at least 6 months;
- Received treatment for RA on an outpatient basis and experienced an inadequate response or intolerance to treatment with at least 1 anti-TNF alpha therapy (etanercept, infliximab or adalimumab);
- Must have received MTX for a minimum of 12 weeks, with the last 4 weeks, prior to screening at a stable dose;
- Participants with swollen joint count (SJC) and tender joint count (TJC) of at least 8 joints at screening and at randomization;
- Radiographic evidence of at least 1 joint with a definite erosion due to RA;
- Participants of reproductive potential must be using reliable contraceptive methods.
Exclusion Criteria:
- Bone or joint surgery within 8 weeks prior to screening or joint surgery planned within 24 weeks of randomization;
- Class IV functional status of RA;
- Previous treatment within 6 months with intravenous gamma globulin, or the Prosorba column;
- Intraarticular or parenteral corticosteroids within 4 weeks prior to screening visit;
- With a live vaccine within 4 weeks prior to randomization;
- Previous treatment with rituximab or other cell-depleting therapies;
- Concurrent treatment with any disease-modifying anti-rheumatic drug (except for MTX) or any anti-TNF alfa factor or other biologic therapy;
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies;
- Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders;
- Known contraindications to receiving rituximab;
- Known active bacterial, viral, fungal, mycobacterial or other infection;
- History of recurrent significant infection or history of recurrent bacterial infections;
- Primary or secondary immunodeficiency (history of, or currently active);
- History of cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that have been excised and cured);
- Women who are pregnant or breast-feeding;
- History of alcohol, drug or chemical abuse within 6 months prior to screening;
- Neuropathies and neurovasculopathies which might interfere with pain evaluation;
- Participants with poor peripheral venous access;
- Intolerance or contraindications to oral or intravenous corticosteroids.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo Plus Methotrexate
Rituximab plus Methotrexate
Arm Description
Participants will be administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg per os (p.o.) or parenterally once a week up to 24 weeks and will be followed up to Week 104.
Participants will be administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and will be followed up to Week 104.
Outcomes
Primary Outcome Measures
Number of Participants With American College of Rheumatology 20 Response at Week 24
American College of Rheumatology (ACR) 20 response is defined as >= 20% improvement (reduction) in score compared with baseline for both tender joint count (TJC)-68 joints and swollen joint count (SJC)-66 joints, as well as for 3 of the additional 5 ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) ranging from score 0 (no pain) to 100 (unbearable pain); Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS ranging score 0 (no disease activity) to 100 (maximum disease activity); Health Assessment Questionnaire (HAQ):8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do) for a total possible score of 0 (best) to 3 (worst); and acute-phase reactant, either C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR).
Secondary Outcome Measures
Number of Participants With an ACR 50 Response at Week 24
ACR 50 response is defined as a >= 50% improvement (reduction) in score compared with baseline for both TJC -68 joints and SJC -66 joints, as well as for 3 of the additional 5 ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a VAS ranging from score '0'=no pain to score '100'=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS ranging from score '0'=no disease activity to score '100'=maximum disease activity; HAQ : Health Assessment Questionnaire (HAQ):which included 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do), where the sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst); and acute-phase reactant, either CRP or ESR.
Number of Participants With ACR 70 Response at Week 24
ACR 70 response is defined as a >= 70% improvement (reduction) in score compared with baseline for both TJC -68 joints and SJC -66 joints, as well as for 3 of the additional 5 ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a VAS ranging from score '0'=no pain to score '100'=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS ranging from score '0'=no disease activity to score '100'=maximum disease activity; HAQ : Health Assessment Questionnaire (HAQ):which included 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do), where the sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst); and acute-phase reactant, either CRP or ESR.
Mean Change From Baseline in Disease Activity Score of 28 Joints at Week 24
The disease activity score (DAS28) is an evaluation index of rheumatoid arthritis. The DAS28 applies a mathematical formula based on the following parameters: 1. TJC-28 joints, 2. SJC -28 joints, 3. ESR or CRP measurement, 4. Participant's judgement on his own overall health (global health [GH]) status expressed by a VAS (0 [no disease activity] to 100 [maximum disease activity]). The mathematical formula is 0.56 × √28TJC + 0.28 × √28SJC + 0.7 x loge ESR + 0.014 × GH. The DAS28 scale ranges from score of 0 to 10, where lower scores indicate best disease control and higher scores indicate worsening of disease. Change from Baseline = difference between the score at Week 24 and the score at Baseline.
Percentage of Participants With DAS28 Low Disease Activity and DAS28 Remission at Week 24
The DAS28 is an evaluation index of RA. The DAS28 applies a mathematical formula based on the following parameters: 1. TJC- 28 joints, 2. SJC- 28 joints, 3. ESR or CRP measurement, 4. Participant's judgement on his own overall health status (GH) expressed by a visual analogue scale VAS (0 [no disease activity] to 100 [maximum disease activity]). The mathematical formula is 0.56 × √28TJC + 0.28 × √28SJC + 0.7 x loge ESR + 0.014 × GH. The DAS28 scale ranges from score of 0 to 10. A participant was categorized as having low disease activity, if participant's DAS28 score was <= 3.2, and was categorized as having clinical remission if participant's DAS28 score was < 2.6.
Number of Participants With Good, Moderate, or no European League Against Rheumatism Responses at Week 24
European League Against Rheumatism (EULAR) response is defined based on the DAS28 score and the EULAR response criteria (Van Gestel et al, 1996 and 1999). The DAS28 scale ranges from score of 0 to 10, where lower scores indicate best disease control and higher scores indicate worsening of disease. At a given visit, participants with a DAS28 score of < 3.2 are considered good responders if the change from baseline in their DAS28 score is >1.2. Participants with a DAS28 score >= 3.2 to 5.1 are considered moderate responders if the change from baseline in their DAS28 score is <=1.2 to >=0.6. Participants with DAS28 score >5.1 are considered non-responders if the change from baseline in their DAS28 score is <=1.2 to >=0.6.
Percentage Change From Baseline in the ACR Core Set (SJC, TJC, Patient's and Physician's Global Assessments, Health Assessment Questionnaire, Pain, C-Reactive Protein, and Erythrocyte Sedimentation Rate) Score
Percentage change in the scores of the following parameters of ACR core set relative to respective baseline scores in both study arms was analyzed : SJC (28 and 66 joints) and TJC (28 and 66 joints), patient's global assessment and physician's global assessment based on disease activity (both are expressed by VAS [0 = no disease activity to 100 = maximum disease activity]), HAQ (based on HAQ disability index [HAQDI]) which included 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do), where the sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst), pain assessment using a VAS ranging from score 0 (no pain) to 100 (unbearable pain), CRP concentration, and ESR.
Mean Change From Baseline of Short Form 36 Total Scores at Week 24
The Short Form (SF)-36 determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual daily activities because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems since last month; 7) limitations in usual work (house hold and outside) due to emotional problems 8) current and 1 year past status of health 9) general mental health. Transforming and standardizing these domains leads to the calculation of the physical component summary and mental component summary measures. Scores on each item were summed and averaged (range 0 [worst] to 100 [best]); increase in score from baseline indicated improvement. Change from Baseline = difference between the score at Week 24 and the score at Baseline.
Number of Participants With Categorical Change From Baseline in the Physical Component Scores of SF-36
The SF-36 determined participants' overall quality of life by assessing :1) limitations in physical functioning due to health problems; 2) limitations in usual daily activities because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems since last month; 7) limitations in usual work (house hold and outside) due to emotional problems 8) current and 1 year past status of health 9) general mental health. Scores on physical component were summed and averaged (range 0 [worst] to 100 [best]); If participants' had shown change from baseline in physical health component score >5.42, it was considered as improved; score between -5.42 to 5.42 was considered as unchanged, and score < -5.42 was considered as worsened. Change from Baseline = difference between the score of physical component at Week 24 and the score at Baseline.
Number of Participants With Change From Baseline in the Mental Component Scores of SF-36
The SF-36 determined participants' overall quality of life by assessing :1) limitations in physical functioning due to health problems; 2) limitations in usual daily activities because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems since last month; 7) limitations in usual work (house hold and outside) due to emotional problems 8) current and 1 year past status of health 9) general mental health. Scores on mental component were summed and averaged (range = 0 [worst]-100 [best]); increase from baseline indicated improvement. If participants' had shown change from baseline in mental health score >6.33, it was considered as improved; scores between -6.33 to 6.33 was considered unchanged, and score <-6.33 was considered as worsened. Change from Baseline = difference between the mental component score at Week 24 and the score at Baseline.
Mean Change From Baseline in the Genant-modified Sharp Joint Space Narrowing Score, Genant-modified Sharp Total Score, and Erosion Score
The Genant-modified Sharp scoring system assesses structural damage due to rheumatoid arthritis in radiographs. A score for erosions of 0-3.5 (8 gradations) is assigned for 14 joints in each hand and wrist, and 6 joints in each foot. Joint space narrowing scores of 0-4 (9 gradations) are assigned to 13 joints in each hand and 6 joints in each foot. The maximum erosion score is 40 x 3.5 = 140. The maximum joint space narrowing score is 38 x 4.0 = 152. Both the erosion and joint space narrowing scores are normalized to 145 and are added together for a maximum total Genant-modified Sharp score of 290. For all the three radiograph assessment, the minimum score is 0. A higher score indicates more damage and a negative change score indicates improvement. The change in score is to be calculated as: Change from Baseline = difference between the score at Weeks 24, 56, or 104 and the score at Baseline.
Percentage of Participants Without Erosive Progression
The Genant-modified Sharp scoring system assesses structural damage due to rheumatoid arthritis in radiographs. A score for erosions of 0-3.5 (8 gradations) is assigned for 14 joints in each hand and wrist, and 6 joints in each foot. The maximum erosion score is 40 x 3.5 = 140 which is normalized to 145. The minimum score is 0 and the maximum score is 145. A higher score indicates more damage and negative change score indicates improvement.
Full Information
NCT ID
NCT00468546
First Posted
April 30, 2007
Last Updated
August 30, 2016
Sponsor
Hoffmann-La Roche
Collaborators
Biogen
1. Study Identification
Unique Protocol Identification Number
NCT00468546
Brief Title
A Study to Evaluate the Safety and Efficacy of MabThera (Rituximab) in Combination With Methotrexate (MTX) in Participants With Active Rheumatoid Arthritis Who Failed on Anti-Tumor Necrosis Factor Alpha Therapy
Official Title
A Randomized, Placebo-controlled, Double-blind, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Alpha Therapies
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
May 2003 (undefined)
Primary Completion Date
January 2005 (Actual)
Study Completion Date
July 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
Collaborators
Biogen
4. Oversight
5. Study Description
Brief Summary
This study will assess the safety and efficacy of rituximab combined with MTX in participants with active rheumatoid arthritis (RA) who have had an inadequate response to anti-Tumor Necrosis (TNF) alpha therapy. The anticipated time in the study is up to 2 years and the target sample size is 500 participants. Eligible participants may receive re-treatment with rituximab under a separate protocol WA17531.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
520 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo Plus Methotrexate
Arm Type
Placebo Comparator
Arm Description
Participants will be administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg per os (p.o.) or parenterally once a week up to 24 weeks and will be followed up to Week 104.
Arm Title
Rituximab plus Methotrexate
Arm Type
Experimental
Arm Description
Participants will be administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and will be followed up to Week 104.
Intervention Type
Drug
Intervention Name(s)
MabThera/Rituxan
Intervention Description
1
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
2
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
3
Primary Outcome Measure Information:
Title
Number of Participants With American College of Rheumatology 20 Response at Week 24
Description
American College of Rheumatology (ACR) 20 response is defined as >= 20% improvement (reduction) in score compared with baseline for both tender joint count (TJC)-68 joints and swollen joint count (SJC)-66 joints, as well as for 3 of the additional 5 ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) ranging from score 0 (no pain) to 100 (unbearable pain); Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS ranging score 0 (no disease activity) to 100 (maximum disease activity); Health Assessment Questionnaire (HAQ):8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do) for a total possible score of 0 (best) to 3 (worst); and acute-phase reactant, either C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR).
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Number of Participants With an ACR 50 Response at Week 24
Description
ACR 50 response is defined as a >= 50% improvement (reduction) in score compared with baseline for both TJC -68 joints and SJC -66 joints, as well as for 3 of the additional 5 ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a VAS ranging from score '0'=no pain to score '100'=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS ranging from score '0'=no disease activity to score '100'=maximum disease activity; HAQ : Health Assessment Questionnaire (HAQ):which included 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do), where the sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst); and acute-phase reactant, either CRP or ESR.
Time Frame
Week 24
Title
Number of Participants With ACR 70 Response at Week 24
Description
ACR 70 response is defined as a >= 70% improvement (reduction) in score compared with baseline for both TJC -68 joints and SJC -66 joints, as well as for 3 of the additional 5 ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a VAS ranging from score '0'=no pain to score '100'=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS ranging from score '0'=no disease activity to score '100'=maximum disease activity; HAQ : Health Assessment Questionnaire (HAQ):which included 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do), where the sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst); and acute-phase reactant, either CRP or ESR.
Time Frame
Week 24
Title
Mean Change From Baseline in Disease Activity Score of 28 Joints at Week 24
Description
The disease activity score (DAS28) is an evaluation index of rheumatoid arthritis. The DAS28 applies a mathematical formula based on the following parameters: 1. TJC-28 joints, 2. SJC -28 joints, 3. ESR or CRP measurement, 4. Participant's judgement on his own overall health (global health [GH]) status expressed by a VAS (0 [no disease activity] to 100 [maximum disease activity]). The mathematical formula is 0.56 × √28TJC + 0.28 × √28SJC + 0.7 x loge ESR + 0.014 × GH. The DAS28 scale ranges from score of 0 to 10, where lower scores indicate best disease control and higher scores indicate worsening of disease. Change from Baseline = difference between the score at Week 24 and the score at Baseline.
Time Frame
From Baseline (Day 1) to Week 24
Title
Percentage of Participants With DAS28 Low Disease Activity and DAS28 Remission at Week 24
Description
The DAS28 is an evaluation index of RA. The DAS28 applies a mathematical formula based on the following parameters: 1. TJC- 28 joints, 2. SJC- 28 joints, 3. ESR or CRP measurement, 4. Participant's judgement on his own overall health status (GH) expressed by a visual analogue scale VAS (0 [no disease activity] to 100 [maximum disease activity]). The mathematical formula is 0.56 × √28TJC + 0.28 × √28SJC + 0.7 x loge ESR + 0.014 × GH. The DAS28 scale ranges from score of 0 to 10. A participant was categorized as having low disease activity, if participant's DAS28 score was <= 3.2, and was categorized as having clinical remission if participant's DAS28 score was < 2.6.
Time Frame
Week 24
Title
Number of Participants With Good, Moderate, or no European League Against Rheumatism Responses at Week 24
Description
European League Against Rheumatism (EULAR) response is defined based on the DAS28 score and the EULAR response criteria (Van Gestel et al, 1996 and 1999). The DAS28 scale ranges from score of 0 to 10, where lower scores indicate best disease control and higher scores indicate worsening of disease. At a given visit, participants with a DAS28 score of < 3.2 are considered good responders if the change from baseline in their DAS28 score is >1.2. Participants with a DAS28 score >= 3.2 to 5.1 are considered moderate responders if the change from baseline in their DAS28 score is <=1.2 to >=0.6. Participants with DAS28 score >5.1 are considered non-responders if the change from baseline in their DAS28 score is <=1.2 to >=0.6.
Time Frame
Week 24
Title
Percentage Change From Baseline in the ACR Core Set (SJC, TJC, Patient's and Physician's Global Assessments, Health Assessment Questionnaire, Pain, C-Reactive Protein, and Erythrocyte Sedimentation Rate) Score
Description
Percentage change in the scores of the following parameters of ACR core set relative to respective baseline scores in both study arms was analyzed : SJC (28 and 66 joints) and TJC (28 and 66 joints), patient's global assessment and physician's global assessment based on disease activity (both are expressed by VAS [0 = no disease activity to 100 = maximum disease activity]), HAQ (based on HAQ disability index [HAQDI]) which included 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do), where the sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst), pain assessment using a VAS ranging from score 0 (no pain) to 100 (unbearable pain), CRP concentration, and ESR.
Time Frame
From Baseline (Day 1) to Week 24
Title
Mean Change From Baseline of Short Form 36 Total Scores at Week 24
Description
The Short Form (SF)-36 determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual daily activities because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems since last month; 7) limitations in usual work (house hold and outside) due to emotional problems 8) current and 1 year past status of health 9) general mental health. Transforming and standardizing these domains leads to the calculation of the physical component summary and mental component summary measures. Scores on each item were summed and averaged (range 0 [worst] to 100 [best]); increase in score from baseline indicated improvement. Change from Baseline = difference between the score at Week 24 and the score at Baseline.
Time Frame
From Baseline (Day 1) to Week 24
Title
Number of Participants With Categorical Change From Baseline in the Physical Component Scores of SF-36
Description
The SF-36 determined participants' overall quality of life by assessing :1) limitations in physical functioning due to health problems; 2) limitations in usual daily activities because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems since last month; 7) limitations in usual work (house hold and outside) due to emotional problems 8) current and 1 year past status of health 9) general mental health. Scores on physical component were summed and averaged (range 0 [worst] to 100 [best]); If participants' had shown change from baseline in physical health component score >5.42, it was considered as improved; score between -5.42 to 5.42 was considered as unchanged, and score < -5.42 was considered as worsened. Change from Baseline = difference between the score of physical component at Week 24 and the score at Baseline.
Time Frame
From Baseline (Day 1) to Week 24
Title
Number of Participants With Change From Baseline in the Mental Component Scores of SF-36
Description
The SF-36 determined participants' overall quality of life by assessing :1) limitations in physical functioning due to health problems; 2) limitations in usual daily activities because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems since last month; 7) limitations in usual work (house hold and outside) due to emotional problems 8) current and 1 year past status of health 9) general mental health. Scores on mental component were summed and averaged (range = 0 [worst]-100 [best]); increase from baseline indicated improvement. If participants' had shown change from baseline in mental health score >6.33, it was considered as improved; scores between -6.33 to 6.33 was considered unchanged, and score <-6.33 was considered as worsened. Change from Baseline = difference between the mental component score at Week 24 and the score at Baseline.
Time Frame
From Baseline (Day 1) to Week 24
Title
Mean Change From Baseline in the Genant-modified Sharp Joint Space Narrowing Score, Genant-modified Sharp Total Score, and Erosion Score
Description
The Genant-modified Sharp scoring system assesses structural damage due to rheumatoid arthritis in radiographs. A score for erosions of 0-3.5 (8 gradations) is assigned for 14 joints in each hand and wrist, and 6 joints in each foot. Joint space narrowing scores of 0-4 (9 gradations) are assigned to 13 joints in each hand and 6 joints in each foot. The maximum erosion score is 40 x 3.5 = 140. The maximum joint space narrowing score is 38 x 4.0 = 152. Both the erosion and joint space narrowing scores are normalized to 145 and are added together for a maximum total Genant-modified Sharp score of 290. For all the three radiograph assessment, the minimum score is 0. A higher score indicates more damage and a negative change score indicates improvement. The change in score is to be calculated as: Change from Baseline = difference between the score at Weeks 24, 56, or 104 and the score at Baseline.
Time Frame
From Baseline (Day 1) to Weeks (W) 24, 56, and 104
Title
Percentage of Participants Without Erosive Progression
Description
The Genant-modified Sharp scoring system assesses structural damage due to rheumatoid arthritis in radiographs. A score for erosions of 0-3.5 (8 gradations) is assigned for 14 joints in each hand and wrist, and 6 joints in each foot. The maximum erosion score is 40 x 3.5 = 140 which is normalized to 145. The minimum score is 0 and the maximum score is 145. A higher score indicates more damage and negative change score indicates improvement.
Time Frame
Up to Week 104
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult participants 18-80 years of age with active RA for at least 6 months;
Received treatment for RA on an outpatient basis and experienced an inadequate response or intolerance to treatment with at least 1 anti-TNF alpha therapy (etanercept, infliximab or adalimumab);
Must have received MTX for a minimum of 12 weeks, with the last 4 weeks, prior to screening at a stable dose;
Participants with swollen joint count (SJC) and tender joint count (TJC) of at least 8 joints at screening and at randomization;
Radiographic evidence of at least 1 joint with a definite erosion due to RA;
Participants of reproductive potential must be using reliable contraceptive methods.
Exclusion Criteria:
Bone or joint surgery within 8 weeks prior to screening or joint surgery planned within 24 weeks of randomization;
Class IV functional status of RA;
Previous treatment within 6 months with intravenous gamma globulin, or the Prosorba column;
Intraarticular or parenteral corticosteroids within 4 weeks prior to screening visit;
With a live vaccine within 4 weeks prior to randomization;
Previous treatment with rituximab or other cell-depleting therapies;
Concurrent treatment with any disease-modifying anti-rheumatic drug (except for MTX) or any anti-TNF alfa factor or other biologic therapy;
History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies;
Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders;
Known contraindications to receiving rituximab;
Known active bacterial, viral, fungal, mycobacterial or other infection;
History of recurrent significant infection or history of recurrent bacterial infections;
Primary or secondary immunodeficiency (history of, or currently active);
History of cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that have been excised and cured);
Women who are pregnant or breast-feeding;
History of alcohol, drug or chemical abuse within 6 months prior to screening;
Neuropathies and neurovasculopathies which might interfere with pain evaluation;
Participants with poor peripheral venous access;
Intolerance or contraindications to oral or intravenous corticosteroids.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Chair
Facility Information:
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
City
Mesa
State/Province
Arizona
ZIP/Postal Code
85208
Country
United States
City
Paradise Valley
State/Province
Arizona
ZIP/Postal Code
85253
Country
United States
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90045
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
City
Rancho Mirage
State/Province
California
ZIP/Postal Code
92270
Country
United States
City
Santa Maria
State/Province
California
ZIP/Postal Code
93454
Country
United States
City
Upland
State/Province
California
ZIP/Postal Code
91786
Country
United States
City
Danbury
State/Province
Connecticut
ZIP/Postal Code
06810
Country
United States
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
City
Delray Beach
State/Province
Florida
ZIP/Postal Code
33484
Country
United States
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33334
Country
United States
City
Jupiter
State/Province
Florida
ZIP/Postal Code
33458
Country
United States
City
Largo
State/Province
Florida
ZIP/Postal Code
33773
Country
United States
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
City
Boise
State/Province
Idaho
ZIP/Postal Code
83702
Country
United States
City
Coeur D'alene
State/Province
Idaho
ZIP/Postal Code
83814
Country
United States
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5149
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
City
Shreverport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49048
Country
United States
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48910
Country
United States
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
City
St Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
City
Albany
State/Province
New York
ZIP/Postal Code
12206
Country
United States
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
City
Rochester
State/Province
New York
ZIP/Postal Code
14618
Country
United States
City
Smithtown
State/Province
New York
ZIP/Postal Code
11787
Country
United States
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7600
Country
United States
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267-0563
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45402
Country
United States
City
Mayfield
State/Province
Ohio
ZIP/Postal Code
44143
Country
United States
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73109
Country
United States
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74135
Country
United States
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19141
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19152
Country
United States
City
Amarillo
State/Province
Texas
ZIP/Postal Code
79124
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
City
Waco
State/Province
Texas
ZIP/Postal Code
76708
Country
United States
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53717
Country
United States
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
City
Gent
ZIP/Postal Code
9000
Country
Belgium
City
Liege
ZIP/Postal Code
4000
Country
Belgium
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2S2
Country
Canada
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1L7
Country
Canada
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 2B6
Country
Canada
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4V2
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X5
Country
Canada
City
Le Kremlin Bicetre
ZIP/Postal Code
94275
Country
France
City
Montpellier
ZIP/Postal Code
34295
Country
France
City
Paris
ZIP/Postal Code
75679
Country
France
City
Rouen
ZIP/Postal Code
76031
Country
France
City
Strasbourg
ZIP/Postal Code
67098
Country
France
City
Toulouse
ZIP/Postal Code
31059
Country
France
City
Tours
ZIP/Postal Code
37044
Country
France
City
Berlin
ZIP/Postal Code
10117
Country
Germany
City
Dresden
ZIP/Postal Code
01067
Country
Germany
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
City
Ratingen
ZIP/Postal Code
40882
Country
Germany
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany
City
Cork
Country
Ireland
City
Dublin
ZIP/Postal Code
4
Country
Ireland
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
City
Haifa
ZIP/Postal Code
3339419
Country
Israel
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
City
Petach Tikva
ZIP/Postal Code
4941492
Country
Israel
City
Ramat Gan
ZIP/Postal Code
5262000
Country
Israel
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
City
Udine
State/Province
Friuli-Venezia Giulia
ZIP/Postal Code
33100
Country
Italy
City
Arenzano
State/Province
Liguria
ZIP/Postal Code
16011
Country
Italy
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
City
Brescia
State/Province
Lombardia
ZIP/Postal Code
25123
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20157
Country
Italy
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56100
Country
Italy
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
City
Drammen
ZIP/Postal Code
3004
Country
Norway
City
Lillehammer
ZIP/Postal Code
2609
Country
Norway
City
Oslo
ZIP/Postal Code
0370
Country
Norway
City
Tromsø
ZIP/Postal Code
9038
Country
Norway
City
Cannock
ZIP/Postal Code
WS11 5XY
Country
United Kingdom
City
Leeds
ZIP/Postal Code
LS7 4SA
Country
United Kingdom
City
London
ZIP/Postal Code
E11 1NR
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M41 5SL
Country
United Kingdom
City
Newcastle Upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
City
Wirral
ZIP/Postal Code
CH49 5PE
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
22127691
Citation
Lal P, Su Z, Holweg CT, Silverman GJ, Schwartzman S, Kelman A, Read S, Spaniolo G, Monroe JG, Behrens TW, Townsend MJ. Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment. Arthritis Rheum. 2011 Dec;63(12):3681-91. doi: 10.1002/art.30596.
Results Reference
derived
PubMed Identifier
18512710
Citation
Keystone E, Burmester GR, Furie R, Loveless JE, Emery P, Kremer J, Tak PP, Broder MS, Yu E, Cravets M, Magrini F, Jost F. Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti-tumor necrosis factor therapy. Arthritis Rheum. 2008 Jun 15;59(6):785-93. doi: 10.1002/art.23715.
Results Reference
derived
Learn more about this trial
A Study to Evaluate the Safety and Efficacy of MabThera (Rituximab) in Combination With Methotrexate (MTX) in Participants With Active Rheumatoid Arthritis Who Failed on Anti-Tumor Necrosis Factor Alpha Therapy
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