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.
This study has been completed.
Information provided by (Responsible Party):
First received: July 17, 2007
Last updated: May 16, 2016
Last verified: May 2016
This single arm study will evaluate the safety and efficacy of MabThera in participants with active rheumatoid arthritis who have had an inadequate response to prior treatment with DMARDs and/or anti-TNF alpha agent. Participants will be treated with MabThera 1000 milligrams (mg) intravenously (IV) on days 1 and 15. Participants were followed every 8 weeks to complete 24 weeks of follow-up. After completion of the Week 24 visit, the participants were followed every 3 months for up to 18 months for an overall study duration of 24 months (104 weeks). After week 36, eligible participants who achieve moderate or good response according to the European League Against Rheumatism (EULAR) response criteria will receive re-treatment with MabThera. Participants will receive concomitant treatment with DMARDs, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics throughout the study period. The anticipated time on study treatment is 2 years, and the target sample size is 200 participants.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
Resource links provided by NLM:
U.S. FDA Resources
Further study details as provided by Hoffmann-La Roche:
Primary Outcome Measures:
- 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) ] [ Designated as safety issue: No ]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.
Secondary Outcome Measures:
- Mean Change From Baseline in Disease Activity Score Based on 28 Joints (DAS 28) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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.
|Study Start Date:||June 2005|
|Study Completion Date:||November 2012|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Drug: Rituximab [MabThera/Rituxan]
1000 mg IV on days 1 and 15
Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00503425
Please refer to this study by its ClinicalTrials.gov identifier: NCT00503425
|Ashkelon, Israel, 78306|
|Beer Sheva, Israel, 8410101|
|Beer Yaakov, Israel, 6093000|
|Hadera, Israel, 38100|
|Haifa, Israel, 3109601|
|Haifa, Israel, 3339419|
|Haifa, Israel, 34362|
|Holon, Israel, 58100|
|Jerusalem, Israel, 91240|
|Kfar Saba, Israel, 44281|
|Naharia, Israel, 22100|
|Nahariya, Israel, 22100|
|Nazareth, Israel, 16100|
|Petach Tikva, Israel, 4941492|
|Rehovot, Israel, 76100|
|Tel Aviv, Israel, 6423906|
Sponsors and Collaborators
|Study Director:||Clinical Trials||Hoffmann-La Roche|