A Study of MabThera (Rituximab) in Participants With Rheumatoid Arthritis Who Have Had an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARD) and/or Anti-Tumor Necrosis Factor (Anti-TNF) Therapy.
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|ClinicalTrials.gov Identifier: NCT00503425|
Recruitment Status : Completed
First Posted : July 18, 2007
Results First Posted : June 23, 2016
Last Update Posted : August 15, 2017
|Condition or disease||Intervention/treatment||Phase|
|Rheumatoid Arthritis||Drug: Rituximab [MabThera/Rituxan]||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||215 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open Label Study to Assess the Safety and Effect on Disease Activity of MabThera in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Prior Treatment With DMARDs and/or One Anti-TNF Alpha Agent|
|Actual Study Start Date :||June 30, 2005|
|Actual Primary Completion Date :||May 26, 2013|
|Actual Study Completion Date :||May 26, 2013|
Drug: Rituximab [MabThera/Rituxan]
1000 mg IV on days 1 and 15
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to study withdrawal or follow-up (Approximately 104 weeks) ]An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants with non-serious AEs was exclusive of SAEs.
- Mean Change From Baseline in Disease Activity Score Based on 28 Joints (DAS 28) at Week 24 [ Time Frame: Baseline, Week 24 ]DAS28 score is a measure of participant's disease activity calculated using tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], participant's global assessment of disease activity (PGH) [visual analog scale (VAS): 0=no disease activity to 100=maximum disease activity] and erythrocyte sedimentation rate (ESR). DAS28 was calculated according to following formula: 0.56 multiplied by (*) square root (√) of TJC] plus (+) [0.28*√SJC]+[0.70*the natural logarithm (ln) ESR]+[0.014*PGH]. Total possible score of 0 to approximately 10, where higher scores represented higher disease activity. Scores below 2.6 indicated clinical remission, score of less than or equals to (</=) 3.2 indicated low disease activity, score of </=5.1 indicated moderate disease activity, scores above 5.1 indicated high or severe disease. Rituximab was administered as needed during episodes of inflammation for up to 5 courses. Change from baseline in DAS28 to Week 24 was reported for all 5 courses.
- Percentage of Participants Whose DAS28 Improved by Greater Than (>) 1.2 at Week 24 [ Time Frame: Week 24 ]DAS28 score is a measure of participant's disease activity calculated using TJC28, SJC28, PGH [VAS: 0=no disease activity to 100=maximum disease activity] and ESR. DAS28 was calculated according to following formula: [0.56*√TJC] + [0.28*√SJC] + [0.70*ln ESR] + [0.014*PGH]. Total possible score of 0 to approximately 10, where higher scores represented higher disease activity. Scores below 2.6 indicated clinical remission, score of </= 3.2 indicated low disease activity, score of </= 5.1 indicated moderate disease activity, and scores above 5.1 indicated high or severe disease. Rituximab was administered as needed during episodes of inflammation for up to 5 courses. Change from baseline in DAS28 to Week 24 was reported for all 5 courses. Participants whose DAS28 score improved by 1.2 score were reported.
- Percentage of Participants With EULAR DAS 28 Response at Week 24 [ Time Frame: Week 24 ]Clinical response was assessed according to EULAR categorical DAS28 response criteria, which defined clinically meaningful improvement at Week 24. EULAR response was based on change from baseline (COB) in DAS28 score and also on actual DAS28 score, at Week 24. DAS28 score= participant's disease activity calculated using TJC28, SJC28, PGH [VAS: 0=no disease activity to 100=maximum disease activity] and ESR. DAS28 was calculated by following formula: 0.56*√TJC+(0.28*√SJC)+(0.70*ln ESR)+(0.014*PGH). Total possible score=0-10, higher scores represented higher disease activity. Scores below 2.6: clinical remission, </=3.2: low disease activity, </=5.1: moderate disease activity, above 5.1: severe disease. EULAR Good response: DAS28</=3.2; COB<-1.2. Moderate response: DAS28</=3.2 or >3.2 to </=5.1 or >5.1; COB <-1.2 or <-0.6 to greater than or equal to (>/=)-1.2. No response: DAS28 </=3.2 or > 3.2 to </=5.1 or >5.1; COB <-0.6 to >/=-1.2 or >/=-0.6. EULAR response was reported for 5 courses.
- Change From Baseline in Bone Density Score at Weeks 48 and 104 [ Time Frame: Baseline, Weeks 48 and 104 (End of treatment) ]Bone density or bone mineral density (BMD) is the amount of bone mineral in bone tissue. BMD test results are compared to the ideal or peak BMD of a healthy 30-year-old adult, and results are provided as T-score. A score of 0 means BMD is equal to the norm for a healthy young adult. Differences between observed BMD and that of the healthy young adult norm are measured in units called standard deviations (SDs). The more standard deviations below 0, indicated as negative numbers, lower the BMD higher the risk of fracture. SD + 1 to -1 indicates normal BMD; SD between -1 to -2.5 indicates low bone mass, SD -2.5 or lower indicates osteoporosis. Change in bone density was measured in participants who were not treated with biphosphonates by Dual Energy X-Ray Absorptiometry. Change in bone density was assessed at baseline and at Weeks 48 and 104. Change from baseline in bone density score was reported for all 5 courses.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00503425
|Ashkelon, Israel, 78306|
|Soroka Medical Center; Reumatology|
|Beer Sheva, Israel, 8410101|
|Assaf Harofe; Dept of Medicine B|
|Beer Yaakov, Israel, 6093000|
|Hillel Yaffe MC; Internal C - Rheumatology|
|Hadera, Israel, 38100|
|Rambam Medical Center; Rheumatology|
|Haifa, Israel, 3109601|
|Bnei Zion Medical Center; Rheumatology|
|Haifa, Israel, 3339419|
|Carmel Hospital; Rheumatology Dept|
|Haifa, Israel, 34362|
|Wolfson Hospital; Rheumatology|
|Holon, Israel, 58100|
|Hadassah Mount Scopus Hospital; Rheumatology|
|Jerusalem, Israel, 91240|
|Meir Medical Center; Internal Dept A|
|Kfar Saba, Israel, 44281|
|Shaare Zedek Medical Center; Rheumatology Dept|
|Naharia, Israel, 22100|
|Nahariya Hospital; Rheumatology Dept|
|Nahariya, Israel, 22100|
|EMMS Nazareth; Internal Department A|
|Nazareth, Israel, 16100|
|Beilinson Medical Center; Rheumatology|
|Petach Tikva, Israel, 4941492|
|Kaplan Medical Center; Reumatology|
|Rehovot, Israel, 76100|
|Sourasky / Ichilov Hospital; Rheumatology|
|Tel Aviv, Israel, 6423906|
|Study Director:||Clinical Trials||Hoffmann-La Roche|