Back to resultsExtension Study to Assess the Efficacy and Safety of Repeat Treatment With Rituximab (MabThera) in Participants With Active Rheumatoid Arthritis (RA)
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Rituximab
Methotrexate
Methylprednisolone
Folic Acid
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- participants with active RA
- completed 24 weeks of treatment in WA16291 or WA17043
- eligible for re-treatment, based on clinical symptoms (Disease Activity Score in 28 joints >=2.6)
- females of childbearing potential using reliable contraception
Exclusion Criteria:
- participants who participated in rituximab studies WA16291 or WA17043 but withdrew into the safety follow-up phases of these trials
- previous rituximab non-responders
- current treatment with any other disease-modifying drug (apart from methotrexate), or any anti-tumor necrosis factor alfa, anti-interleukin-1, or other biologic therapies
- participants with known active infection of any kind
- evidence of any new or uncontrolled concomitant disease or development of any new contraindications which would preclude repeat treatment with rituximab
- history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- female participants who are pregnant or breastfeeding
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rituximab
Arm Description
Participants will receive rituximab 1 gram intravenously (IV) on Days 1 and 15 of each course of retreatment. In addition, participants will receive methotrexate 10-25 milligrams per week (mg/week) orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid greater than or equal to (>=) 5 mg/week or equivalent. Participants will receive retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment will be based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab will be continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever is sooner.
Outcomes
Primary Outcome Measures
Percentage of Participants With an American College of Rheumatology 20 (ACR20) Response After First Course
A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in tender joint count (TJC) and swollen joint count (SJC) (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [visual analog scale (VAS): 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR]). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With ACR20 Response After Second Course
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With ACR20 Response After Third Course
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With ACR20 Response After Fourth Course
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With ACR20 Response After Fifth Course
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With ACR20 Response After Sixth Course
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With ACR20 Response After Seventh Course
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Secondary Outcome Measures
Percentage of Participants With ACR50 and ACR70 Response
A participant had an ACR50 and ACR70 response if there was at least a 50% or 70% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of disease activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (CRP or ESR). The ACR50 and ACR70 responses were compared to Baseline in the precursor studies WA16291 or WA17043.
American College of Rheumatology Index of Improvement (ACRn) Response
The ACRn is calculated for each participant by taking the lowest percentage improvement in (1) SJC or (2) TJC or (3) the median of the remaining 5 components of the ACR response (patient's assessment of disease activity; patient's global assessment of pain; physician's assessment of disease activity; participant's assessment of physical function; an acute phase reactant value [either CRP or ESR]). The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA. ACRn scores were calculated considering the original baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With Low Disease Activity and Clinical Remission Based on DAS28-ESR
DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (millimeters per hour [mm/hour]), and Patient's Global Assessment of Disease Activity (VAS: 0=no disease activity to 100=maximum disease activity). DAS28-ESR = 0.56*square root (sqrt)(TJC28) + 0.28*sqrt(SJC28) + 0.70*natural logarithm (ln) (ESR) + 0.014*Patient's Global Assessment of Disease Activity. Total score range: 0-10, higher score=more disease activity. DAS28-ESR <= 3.2 implied low disease activity (LDA) and DAS28-ESR <2.6 = clinical remission.
Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate'
DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and Physician's Global Assessment of Disease Activity (VAS: 0=no disease activity to 100=maximum disease activity). DAS28-ESR = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014*Patient's Global Assessment of Disease Activity. The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (>) 1.2 with a DAS28 score less than or equal to (≤) 3.2; moderate responders had a change from baseline >1.2 with a DAS28 score >3.2 to less than or equal to (≤) 5.1 or a change from baseline >0.6 to ≤1.2 with a DAS28 score ≤5.1.
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at 24 Weeks Following Each Course
The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Participants completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.
Change From Baseline in Total Rheumatoid Factors (RF) at 24 Weeks Following Each Course
Percentage of Participants Who Discontinued Treatment Due to Insufficient Response
Time Since Last Treatment Course
Time since last treatment course = The last day of the last dose of rituximab to date of last contact. Date of last contact is the last available date of efficacy, complete medication start date, laboratory, adverse event assessments, early withdrawal visit, date of last contact, or date of death.
Full Information
NCT ID
NCT02093026
First Posted
March 19, 2014
Last Updated
January 23, 2017
Sponsor
Hoffmann-La Roche
Collaborators
Genentech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02093026
Brief Title
Extension Study to Assess the Efficacy and Safety of Repeat Treatment With Rituximab (MabThera) in Participants With Active Rheumatoid Arthritis (RA)
Official Title
An Open-label Study of the Efficacy and Safety of Re-treatments With Rituximab (MabThera®/Rituxan®) in Patients With Active Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
August 2002 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
Collaborators
Genentech, Inc.
4. Oversight
5. Study Description
Brief Summary
This study will assess the long-term safety and efficacy of repeat treatment courses of rituximab, in combination with methotrexate in a disease-modifying anti-rheumatic drug (DMARD) inadequate responder population of participants who were previously randomized into studies WA16291 (NCT02693210) or WA17043/U2644g (NCT00074438). The study permits multiple re-treatments until the protocol-defined end-of-treatment date (31 December 2011). Participants will then enter a safety follow-up (SFU) period of at least 48 weeks. This will provide at least 7 years follow-up data on all participants initially randomized into WA16291 or WA17043/U2644g. Approximately 600 participants will potentially be eligible to enter this open label extension study from their respective feeder studies.
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 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
465 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab
Arm Type
Experimental
Arm Description
Participants will receive rituximab 1 gram intravenously (IV) on Days 1 and 15 of each course of retreatment. In addition, participants will receive methotrexate 10-25 milligrams per week (mg/week) orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid greater than or equal to (>=) 5 mg/week or equivalent. Participants will receive retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment will be based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab will be continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever is sooner.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
MabThera, Rituxan
Intervention Description
Participants will receive rituximab 1 gram IV on Days 1 and 15 of each course of retreatment.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Participants will receive methotrexate 10-25 mg/week orally or parenterally.
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Intervention Description
Participants will receive methylprednisolone 100 mg IV 30 minutes prior to each rituximab infusion.
Intervention Type
Drug
Intervention Name(s)
Folic Acid
Intervention Description
Participants will receive folic acid >= 5 mg/week or equivalent.
Primary Outcome Measure Information:
Title
Percentage of Participants With an American College of Rheumatology 20 (ACR20) Response After First Course
Description
A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in tender joint count (TJC) and swollen joint count (SJC) (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [visual analog scale (VAS): 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR]). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Time Frame
24 weeks after first course of rituximab (up to approximately 26 weeks)
Title
Percentage of Participants With ACR20 Response After Second Course
Description
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Time Frame
24 weeks after second course of rituximab (median duration of 90.9 weeks)
Title
Percentage of Participants With ACR20 Response After Third Course
Description
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Time Frame
24 weeks after third course of rituximab (median duration of 162.9 weeks)
Title
Percentage of Participants With ACR20 Response After Fourth Course
Description
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Time Frame
24 weeks after fourth course of rituximab (median duration of 232 weeks)
Title
Percentage of Participants With ACR20 Response After Fifth Course
Description
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Time Frame
24 weeks after fifth course of rituximab (median duration of 297.3 weeks)
Title
Percentage of Participants With ACR20 Response After Sixth Course
Description
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Time Frame
24 weeks after sixth course of rituximab (median duration of 354.4 weeks)
Title
Percentage of Participants With ACR20 Response After Seventh Course
Description
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Time Frame
24 weeks after seventh course of rituximab (median duration of 406.7 weeks)
Secondary Outcome Measure Information:
Title
Percentage of Participants With ACR50 and ACR70 Response
Description
A participant had an ACR50 and ACR70 response if there was at least a 50% or 70% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of disease activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (CRP or ESR). The ACR50 and ACR70 responses were compared to Baseline in the precursor studies WA16291 or WA17043.
Time Frame
24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Title
American College of Rheumatology Index of Improvement (ACRn) Response
Description
The ACRn is calculated for each participant by taking the lowest percentage improvement in (1) SJC or (2) TJC or (3) the median of the remaining 5 components of the ACR response (patient's assessment of disease activity; patient's global assessment of pain; physician's assessment of disease activity; participant's assessment of physical function; an acute phase reactant value [either CRP or ESR]). The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA. ACRn scores were calculated considering the original baseline in the precursor studies WA16291 or WA17043.
Time Frame
24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Title
Percentage of Participants With Low Disease Activity and Clinical Remission Based on DAS28-ESR
Description
DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (millimeters per hour [mm/hour]), and Patient's Global Assessment of Disease Activity (VAS: 0=no disease activity to 100=maximum disease activity). DAS28-ESR = 0.56*square root (sqrt)(TJC28) + 0.28*sqrt(SJC28) + 0.70*natural logarithm (ln) (ESR) + 0.014*Patient's Global Assessment of Disease Activity. Total score range: 0-10, higher score=more disease activity. DAS28-ESR <= 3.2 implied low disease activity (LDA) and DAS28-ESR <2.6 = clinical remission.
Time Frame
24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Title
Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate'
Description
DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and Physician's Global Assessment of Disease Activity (VAS: 0=no disease activity to 100=maximum disease activity). DAS28-ESR = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014*Patient's Global Assessment of Disease Activity. The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (>) 1.2 with a DAS28 score less than or equal to (≤) 3.2; moderate responders had a change from baseline >1.2 with a DAS28 score >3.2 to less than or equal to (≤) 5.1 or a change from baseline >0.6 to ≤1.2 with a DAS28 score ≤5.1.
Time Frame
24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Title
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at 24 Weeks Following Each Course
Description
The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Participants completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.
Time Frame
24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Title
Change From Baseline in Total Rheumatoid Factors (RF) at 24 Weeks Following Each Course
Time Frame
24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Title
Percentage of Participants Who Discontinued Treatment Due to Insufficient Response
Time Frame
First, second, third, fourth, fifth, sixth, and seventh course of rituximab (up to a median of approximately 2, 62, 124, 186, 248, 310, and 372 weeks, respectively)
Title
Time Since Last Treatment Course
Description
Time since last treatment course = The last day of the last dose of rituximab to date of last contact. Date of last contact is the last available date of efficacy, complete medication start date, laboratory, adverse event assessments, early withdrawal visit, date of last contact, or date of death.
Time Frame
Baseline up to 10 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
participants with active RA
completed 24 weeks of treatment in WA16291 or WA17043
eligible for re-treatment, based on clinical symptoms (Disease Activity Score in 28 joints >=2.6)
females of childbearing potential using reliable contraception
Exclusion Criteria:
participants who participated in rituximab studies WA16291 or WA17043 but withdrew into the safety follow-up phases of these trials
previous rituximab non-responders
current treatment with any other disease-modifying drug (apart from methotrexate), or any anti-tumor necrosis factor alfa, anti-interleukin-1, or other biologic therapies
participants with known active infection of any kind
evidence of any new or uncontrolled concomitant disease or development of any new contraindications which would preclude repeat treatment with rituximab
history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
female participants who are pregnant or breastfeeding
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
Peoria
State/Province
Arizona
ZIP/Postal Code
85381
Country
United States
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
City
Long Beach
State/Province
California
ZIP/Postal Code
92813
Country
United States
City
Rancho Mirage
State/Province
California
ZIP/Postal Code
92270
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92108
Country
United States
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80920
Country
United States
City
Aventura
State/Province
Florida
ZIP/Postal Code
33180
Country
United States
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33334
Country
United States
City
Largo
State/Province
Florida
ZIP/Postal Code
33773
Country
United States
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
City
Boise
State/Province
Idaho
ZIP/Postal Code
83702
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
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
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55416
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
City
Voorhees
State/Province
New Jersey
ZIP/Postal Code
08043
Country
United States
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
City
Plainview
State/Province
New York
ZIP/Postal Code
11803
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
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
City
Winston Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
City
Beachwood
State/Province
Ohio
ZIP/Postal Code
44122
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
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74104
Country
United States
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74135
Country
United States
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
City
Glendale
State/Province
Wisconsin
ZIP/Postal Code
53217
Country
United States
City
Wausau
State/Province
Wisconsin
ZIP/Postal Code
54401
Country
United States
City
Maroochydore
State/Province
Queensland
ZIP/Postal Code
4558
Country
Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6979
Country
Australia
City
Gent
ZIP/Postal Code
9000
Country
Belgium
City
Curtiba
State/Province
PR
ZIP/Postal Code
80030-110
Country
Brazil
City
Campinas
State/Province
SP
ZIP/Postal Code
13083-888
Country
Brazil
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
04026-000
Country
Brazil
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1L7
Country
Canada
City
St John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1A 5E8
Country
Canada
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4V2
Country
Canada
City
Praha
ZIP/Postal Code
128 50
Country
Czech Republic
City
Heinola
ZIP/Postal Code
18120
Country
Finland
City
Helsinki
ZIP/Postal Code
00290
Country
Finland
City
Köln
ZIP/Postal Code
50924
Country
Germany
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
City
Ratingen
ZIP/Postal Code
40882
Country
Germany
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
City
Haifa
ZIP/Postal Code
3339419
Country
Israel
City
Modena
State/Province
Emilia-Romagna
ZIP/Postal Code
41100
Country
Italy
City
Udine
State/Province
Friuli-Venezia Giulia
ZIP/Postal Code
33100
Country
Italy
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20157
Country
Italy
City
Mexico City
ZIP/Postal Code
06726
Country
Mexico
City
Mexico City
ZIP/Postal Code
10700
Country
Mexico
City
Mexico
ZIP/Postal Code
44620
Country
Mexico
City
Monterrey
ZIP/Postal Code
64460
Country
Mexico
City
Auckland City
ZIP/Postal Code
0620
Country
New Zealand
City
Auckland
ZIP/Postal Code
2025
Country
New Zealand
City
Bialystok
ZIP/Postal Code
15-351
Country
Poland
City
Lublin
ZIP/Postal Code
20-022
Country
Poland
City
Poznan
ZIP/Postal Code
61-545
Country
Poland
City
Warszawa
ZIP/Postal Code
02-637
Country
Poland
City
Wroclaw
ZIP/Postal Code
50-556
Country
Poland
City
Merida
State/Province
Badajoz
ZIP/Postal Code
06800
Country
Spain
City
Santiago de Compostela
State/Province
La Coruña
ZIP/Postal Code
15706
Country
Spain
City
La Laguna
State/Province
Tenerife
ZIP/Postal Code
38320
Country
Spain
City
Madrid
ZIP/Postal Code
28006
Country
Spain
City
Madrid
ZIP/Postal Code
28007
Country
Spain
City
Madrid
ZIP/Postal Code
28046
Country
Spain
City
Sevilla
ZIP/Postal Code
41014
Country
Spain
City
Göteborg
ZIP/Postal Code
413 45
Country
Sweden
City
Stockholm
ZIP/Postal Code
171 76
Country
Sweden
City
Birmingham
ZIP/Postal Code
B29 6JD
Country
United Kingdom
City
Cambridge
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
City
Cannock
ZIP/Postal Code
WS11 5XY
Country
United Kingdom
City
Leeds
ZIP/Postal Code
LS7 4SA
Country
United Kingdom
City
Stoke-on-trent
ZIP/Postal Code
ST6 7AG
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Extension Study to Assess the Efficacy and Safety of Repeat Treatment With Rituximab (MabThera) in Participants With Active Rheumatoid Arthritis (RA)
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