TriangleNCT00422383 · CITED IN SOURCE DOCUMENTS
A Study of Retreatment With MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis (RA)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2015-05-04
This study will evaluate the efficacy and safety of various treatment and retreatment regimens of MabThera. All patients will receive concomitant methotrexate, 10-25mg once weekly either orally or parenterally. The anticipated time on study treatment is 2+ years, and the target sample size is 100-500 individuals.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20)
Percentage of Participants With ACR 50% Improvement Criteria (ACR50) Response at Week 48
Percentage of Participants With a ACR 70% Improvement Criteria (ACR70) Response at Week 48
Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR): Adjusted Mean Change From BL at Week 48
Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category
Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48
Short-Form 36 Health Survey (SF-36) Score
Change in SF-36 Score From BL
Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL)
Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL
Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days
Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL)
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN)
Peripheral CD20+ B Cell Count in Cells/µL
Peripheral CD22+ B Cell Count in Cells/µL
Peripheral CD19+CD27+ B Cell Count in Cells/µL
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL
Peripheral CD3+ T Cell Count in Cells/µL
Change From BL in Peripheral CD3+ T Cell Count
Peripheral CD4+ T Cell Count in Cells/µL
Change From BL in Peripheral CD4+ T Cell Count
Peripheral CD8+ T Cell Count in Cells/µL
Change From BL in Peripheral CD8+ Cell Count
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL
Change From BL in Peripheral CD16+56+ Cell Count
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN
Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative
Anti-Cyclic Citrullinated Peptide (CCP) Antibody Titers at BL in Units Per mL (U/mL)
Change From BL in Anti-CCP Antibody Titers in U/mL
Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN
Change From BL in Complement C3 Protein Level in g/L
Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L
Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN
Change From BL in Complement C4 Protein Level in g/L
Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L
Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers
Percentage of Participants With Positive Recall Antigen Antibody Titers
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * adult patients \>=18 years of age; * RA for \>=6 months; * receiving outpatient treatment; * inadequate response to methotrexate, having received and tolerated it for \>=12 weeks, with a stable dose for \>=4 weeks. Exclusion Criteria: * rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA; * inflammatory joint disease other than RA, or other systemic autoimmune disorder; * diagnosis of juvenile arthritis, or RA before the age of 16; * previous treatment with \>1 biologic agent, any cell-depleting therapies, or concurrent treatment with any biologic agent or DMARD other than methotrexate.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- intervention Names
- Drug: rituximab [MabThera/Rituxan]
- label
- 1
- type
- EXPERIMENTAL
- intervention Names
- Drug: rituximab [MabThera/Rituxan]
- label
- 2
- type
- EXPERIMENTAL
- intervention Names
- Drug: rituximab [MabThera/Rituxan]
- label
- 3
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- 1
- description
- 500mg iv in days 1 and 15, and 500mg iv on days 168 and 182
- name
- rituximab [MabThera/Rituxan]
- type
- DRUG
- arm Group Labels
- 2
- description
- 500mg iv on days 1 and 15, and 1000mg iv on days 168 and 182
- name
- rituximab [MabThera/Rituxan]
- type
- DRUG
- arm Group Labels
- 3
- description
- 1000mg iv on days 1 and 15 and 1000mg iv (or placebo in UK)on days 168 and 182
- name
- rituximab [MabThera/Rituxan]
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- DOUBLE
- who Masked
- PARTICIPANT
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 378
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- ACR20 defined as overall score of ≥20 in ACR number (ACRn) calculation. Overall score defined as lowest percent improvement from baseline (BL) of following 3 measures: tender joint count (TJC; 68 joints), swollen joint count (SJC: 66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (visual analog assessment \[VAS\]), Health Assessment Questionnaire (HAQ), and C-Reactive Protein (CRP). If CRP missing, erythrocyte sedimentation rate (ESR) was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. Last observation carried forward (LOCF) for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR20 set to Non-Responder if ACRn missing
- measure
- Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20)
- time Frame
- Week 48
- secondary Outcomes
- description
- ACR50 was defined as an overall score of 50 in the ACRn calculation. Overall score defined as lowest percent improvement from BL of following 3 measures: TJC (68 joints), SJC (66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (VAS), HAQ, and CRP. If CRP missing, ESR was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. LOCF for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR50 set to Non-Responder if ACRn missing.
- measure
- Percentage of Participants With ACR 50% Improvement Criteria (ACR50) Response at Week 48
- time Frame
- Week 48
- description
- ACR70 was defined as an overall score of 70 in the ACRn calculation. The Overall score defined as lowest percent improvement from BL of following 3 measures: TJC (68 joints), SJC (66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (VAS), HAQ, and CRP. If CRP missing, ESR was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. LOCF for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR70 set to Non-Responder if ACRn missing.
- measure
- Percentage of Participants With a ACR 70% Improvement Criteria (ACR70) Response at Week 48
- time Frame
- Week 48
- description
- DAS28 was calculated according to the following formula: DAS28 equals (=) \[0.56 multiplied by (\*) the square root (√) of TJC\] plus (+) \[0.28 \* √ of SJC\] + (0.70 \* the natural logarithm (ln) ESR in millimeters per hour (mm/h)\] + \[0.014 \* participant's global assessment of disease activity (GH)\]. DAS28-ESR ≥ 5.1 = high disease activity, DAS28-ESR less than or equal to (≤) 3.2 = low disease activity, DAS28-ESR less than (\<) 2.6 = remission.
- measure
- Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR): Adjusted Mean Change From BL at Week 48
- time Frame
- BL, Week 48
- description
- EULAR responses were categorized according to DAS28-ESR score. DAS28-ESR ≤ 3.2 at Week 48 and a change from BL to Week 48 \< -1.2 = good response, DAS28-ESR ≤ 3.2 or greater than (\>) 3.2 and ≤ 5.1 at Week 48 and a change from BL to Week 48 \< -0.6 and ≥ -1.2 = moderate response, DAS28-ESR \> 3.2 and ≤ 5.1 at Week 48 and a change from BL to Week 48 \< -1.2 = moderate response, DAS28-ESR \> 5.1 at Week 48 and a change from BL to Week 48 \< -1.2 = moderate response, DAS28-ESR ≤ 3.2 or \> 3.2 and ≤ 5.1 at Week 48 and a change from BL to Week 48 ≥ -0.6 = no response, DAS28-ESR \> 5.1 at Week 48 and a change from BL to Week 48 \< -0.6 and ≥ -1.2 or ≥ -0.6 = no response.
- measure
- Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category
- time Frame
- Week 48
- description
- FACIT-F scores were obtained from a 13 question self-administered participant questionnaire designed to measure the degree of fatigue experienced by participants in the previous 7 days. Participants responded to the questions using a value between 0 and 4, where 0 indicated "not at all" and 4 indicated "very much." 11 of the 13 questions were negatively stated; indicating the higher the score of the participant's response, the greater their fatigue. These questions were calculated as 4 minus the participants' response, so that a higher score indicated an improvement in health. The scores for the 2 positively stated questions were not changed. The participants' responses were summed to result in an overall score, which are scored 0 to 52 (52 = highest level of functioning). A positive change from BL indicated improvement.
- measure
- Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48
- time Frame
- BL, Week 48
- description
- SF-36 scores were obtained by scoring participants' responses to a 36 item questionnaire. SF-36 evaluated 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health from a range of 1 (better) to 5 (worst). The score for each section was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). These 8 aspects were summarized as physical and mental component scores.
- measure
- Short-Form 36 Health Survey (SF-36) Score
- time Frame
- BL, Week (Wk) 24 and 48
- description
- SF-36 scores were obtained by scoring participants' responses to a 36 item questionnaire. SF-36 evaluated 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health from a range of 1 (better) to 5 (worst). The score for each section was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). These 8 aspects were summarized as physical and mental component scores.
- measure
- Change in SF-36 Score From BL
- time Frame
- BL, Weeks 24 and 48
- description
- Cfirst values were estimated from rituximab serum concentrations by non-compartmental methods using the software WinNonlin Enterprise Version 5.2.
- measure
- Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL)
- time Frame
- Days 1 and 15 (before infusion and 30 minutes following infusion) and Weeks 4, 8, 16, 24, 26, 28, 32, 40, and 48 or early withdrawal and at Weeks 24 and 48 of safety follow-up (1 year period following the completion of study treatment).
- description
- Csecond values were estimated from rituximab serum concentrations by non-compartmental methods using the software WinNonlin Enterprise Version 5.2.
- measure
- Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL
- time Frame
- Days 1 and 15 (before infusion and 30 minutes following infusion) and Weeks 4, 8, 16, 24, 26, 28, 32, 40, and 48 or early withdrawal and at Weeks 24 and 48 of safety follow-up (1 year period following the completion of study treatment).
- description
- t1/2 values were estimated from rituximab serum concentrations by non-compartmental methods using the software WinNonlin Enterprise Version 5.2.
- measure
- Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days
- time Frame
- Days 1 and 15 (before infusion and 30 minutes following infusion) and Weeks 4, 8, 16, 24, 26, 28, 32, 40, and 48 or early withdrawal and at Weeks 24 and 48 of safety follow-up (1 year period following the completion of study treatment).
- description
- Surface expression of CD19 was assessed by fluorescence-activated cell sorting (FACS) analysis as a marker of absolute B lymphocyte count.
- measure
- Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL)
- time Frame
- BL
- description
- Surface expression of CD19 was assessed by FACS analysis as a marker of absolute B lymphocyte count. The LLN was defined as \< 80 cells/µL.
- measure
- Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN)
- time Frame
- BL, Days 1 and 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Full study description
- brief Summary
- This study will evaluate the efficacy and safety of various treatment and retreatment regimens of MabThera. All patients will receive concomitant methotrexate, 10-25mg once weekly either orally or parenterally. The anticipated time on study treatment is 2+ years, and the target sample size is 100-500 individuals.
Source references
- references
- citation
- Rubbert-Roth A, Tak PP, Zerbini C, Tremblay JL, Carreno L, Armstrong G, Collinson N, Shaw TM; MIRROR Trial Investigators. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR). Rheumatology (Oxford). 2010 Sep;49(9):1683-93. doi: 10.1093/rheumatology/keq116. Epub 2010 May 12.
- pmid
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Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice