Clinical trial NCT01332994: A Study of RoActemra/Actemra and, if Initially Inadequately Responded to RoActemra/Actemra, Followed by MabThera/Rituxan in Patients With Rheumatoid Arthritis
Official title: Efficacy and Safety Study of a Sequential Therapy of Tocilizumab (TCZ) and, if Initially Inadequately Responded to Tocilizumab (TCZ), Followed by Rituximab (RTX) in DMARD-IR Patients With Rheumatoid Arthritis (MIRAI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-04-11
Enrollment: 519
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This open-label, multi-center, two-arm, uncontrolled and non-randomized study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with rheumatoid arthritis. Patients will receive 8 mg/kg RoActemra/Actemra intravenously every 4 weeks for 12 weeks and - if adequately responded - for further 12 weeks. Patients, who show an inadequate clinical response after the first 12 weeks to RoActemra/Actemra, will receive 1 g MabThera/Rituxan (rituximab) intravenously at Week 16 and 18. The anticipated time of study treatment is 32 weeks.


Eligibility criteria: Inclusion Criteria:

* Adult patients \>/=18 years of age
* Body weight \< /=130kg
* Active rheumatoid arthritis of at least 6 months duration, diagnosed according to the American College of Rheumatology (ACR) criteria of 1987
* Disease Activity Score (DAS28) of \>3.2
* Inadequate clinical response to a stable dose of traditional Disease-Modifying Anti-Rheumatic Drugs (DMARD)
* Have received permitted DMARDs, one or more; current DMARD therapy must have been at stable dose for at least 4 weeks prior to baseline

Exclusion Criteria:

* Prior treatment with TNF-inhibitors or other biologic DMARD
* Major surgery (including joint surgery) within eight weeks prior to baseline or planned major surgery within the study duration
* Functional class IV (American College of Rheumatology classification)
* Rheumatic autoimmune disease other than rheumatoid arthritis
* History of or current inflammatory joint disease other than rheumatoid arthritis

Primary outcomes:
measure: Percentage of Participants Achieving Remission at Week 16 According to DAS28
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants Achieving Remission According to DAS28 at Weeks 4, 8, and 12
timeFrame: Weeks 4, 8, and 12
measure: Percentage of Participants Achieving Remission According to DAS28 at Weeks 16, 20, 24, and 28 Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Weeks 16, 20, 24, and 28
measure: Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Week 32
measure: Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Nonresponding Participants Treated With Rituximab
timeFrame: Week 32
measure: Percentage of Participants Achieving Low Disease Activity Score (LDAS) According to DAS28
timeFrame: Week 16
measure: Percentage of Participants Achieving LDAS According to DAS28 Among Among Nonresponding Participants Treated With Rituximab
timeFrame: Week 32
measure: Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Weeks 4, 8, and 12
timeFrame: Baseline and Weeks 4, 8, and 12
measure: Percentage of Participants Achieving a Clinically Relevant Reduction in DAS28 From Week 16 to Week 32 Among Nonresponding Participants Treated With Rituximab
timeFrame: Weeks 16 and 32
measure: DAS28 Scores During and After Treatment
timeFrame: Baseline and Weeks 4, 8, 12, 16
measure: DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, and 32
measure: DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab
timeFrame: Baseline and Weeks 4, 8, 12, 16, 24, and 32
measure: DAS28 Scores During Safety Follow-Up Among Nonresponding Participants Treated With Rituximab
timeFrame: Weeks 40, 48, 56, and 66
measure: Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16
timeFrame: Baseline and Weeks 4, 8, 12, and 16
measure: Percentage of Participants Achieving a Response According to EULAR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab
timeFrame: Weeks 16 and 32
measure: Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Baseline and Weeks 20, 24, 28, and 32
measure: Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16
timeFrame: Baseline and Weeks 4, 8, 12, and 16
measure: Percentage of Participants Achieving a Response According to ACR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab
timeFrame: Weeks 16 and 32
measure: Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Baseline and Weeks 20, 24, 28, and 32
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16
timeFrame: Baseline and Weeks 4, 8, 12, and 16
measure: Change From Week 16 to 32 in CDAI and SDAI Scores Among Nonresponding Participants Treated With Rituximab
timeFrame: Weeks 16 and 32
measure: Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Baseline and Weeks 20, 24, 28, and 32
measure: Change From Baseline in Hemoglobin at Weeks 4, 8, 12, and 16
timeFrame: Baseline and Weeks 4, 8, 12, and 16
measure: Change From Baseline in CRP at Weeks 4, 8, 12, and 16
timeFrame: Baseline and Weeks 4, 8, 12, and 16
measure: Change From Baseline in ESR at Weeks 4, 8, 12, and 16
timeFrame: Baseline and Weeks 4, 8, 12, and 16
measure: Change in Hemoglobin From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab
timeFrame: Weeks 16 and 32
measure: Change in CRP From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab
timeFrame: Weeks 16 and 32
measure: Change in ESR From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab
timeFrame: Weeks 16 and 32
measure: Change From Baseline in Hemoglobin at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Baseline and Weeks 20, 24, 28, and 32
measure: Change From Baseline in CRP at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Baseline and Weeks 20, 24, 28, and 32
measure: Change From Baseline in ESR at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Baseline and Weeks 20, 24, 28, and 32
measure: Percentage of Participants Withdrawing From the Study for Insufficient Therapeutic Response
timeFrame: Baseline to Week 16
measure: Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission
timeFrame: Baseline
measure: Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Baseline
measure: Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab
timeFrame: Baseline
measure: Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission
timeFrame: Baseline and Week 16
measure: Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Baseline and Weeks 16, 24, and 32
measure: Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab
timeFrame: Baseline and Weeks 16, 32, 40, 48, and 66
measure: Mean Number of Work Days Missed Per Week
timeFrame: Baseline and Week 16
measure: Quality of Life as Assessed Using Short Form 36 (SF-36)
timeFrame: Baseline and Week 16
measure: Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16
timeFrame: Baseline and Week 16
measure: Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Weeks 16 and 32
measure: Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab
timeFrame: Weeks 16 and 32
measure: Quality of Life as Assessed Using HAQ-DI
timeFrame: Baseline and Week 16
measure: Change From Baseline in Quality of Life as Assessed Using HAQ-DI at Week 16
timeFrame: Baseline and Week 16
measure: Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Weeks 16 and 32
measure: Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Nonresponding Participants Treated With Rituximab
timeFrame: Weeks 16 and 32
measure: Percentage of Participants Achieving a Response According to HAQ-DI Criteria
timeFrame: Baseline and Week 16
measure: Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT)
timeFrame: Baseline and Week 16
measure: Change From Baseline in Quality of Life as Assessed Using FACIT at Week 16
timeFrame: Baseline and Week 16
measure: Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Participants Treated With 8 Courses of Tocilizumab
timeFrame: Weeks 16 and 32
measure: Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Nonresponding Participants Treated With Rituximab
timeFrame: Weeks 16 and 32
Other outcomes:
Locations:
city: Aachen
country: Germany
city: Bad Aibling
country: Germany
city: Bad Bramstedt
country: Germany
city: Bad Nauheim
country: Germany
city: Bad Staffelstein
country: Germany
city: Bayreuth
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Blaubeuren
country: Germany
city: Bonn
country: Germany
city: Bruchhausen-Vilsen
country: Germany
city: Chemnitz
country: Germany
city: Donaueschingen
country: Germany
city: Dresden
country: Germany
city: Dresden
country: Germany
city: Dresden
country: Germany
city: Dresden
country: Germany
city: Düsseldorf
country: Germany
city: Düsseldorf
country: Germany
city: Erfurt
country: Germany
city: Essen
country: Germany
city: Frankfurt Am Main
country: Germany
city: Freiburg
country: Germany
city: Giessen
country: Germany
city: Gommern
country: Germany
city: Goslar
country: Germany
city: Greifswald
country: Germany
city: Göttingen
country: Germany
city: Halle
country: Germany
city: Halle
country: Germany
city: Halle
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Heidelberg
country: Germany
city: Herne
country: Germany
city: Hildesheim
country: Germany
city: Hofheim
country: Germany
city: Jena
country: Germany
city: Kiel
country: Germany
city: Köln
country: Germany
city: Köln
country: Germany
city: Köln
country: Germany
city: Leipzig
country: Germany
city: Leipzig
country: Germany
city: Lingen
country: Germany
city: Ludwigsfelde
country: Germany
city: Mainz
country: Germany
city: Muenchen
country: Germany
city: Mönchengladbach
country: Germany
city: München
country: Germany
city: München
country: Germany
city: Naumburg
country: Germany
city: Naunhof
country: Germany
city: Neuss
country: Germany
city: Neuss
country: Germany
city: Nienburg
country: Germany
city: Olsberg
country: Germany
city: Osnabrück
country: Germany
city: Plochingen
country: Germany
city: Potsdam
country: Germany
city: Ratingen
country: Germany
city: Regensburg
country: Germany
city: Rendsburg
country: Germany
city: Rheine
country: Germany
city: Rostock
country: Germany
city: Saarbruecken
country: Germany
city: Sendenhorst
country: Germany
city: Stuttgart
country: Germany
city: Stuttgart
country: Germany
city: Traunstein
country: Germany
city: Trier
country: Germany
city: Tübingen
country: Germany
city: Ulm
country: Germany
city: Wiesbaden
country: Germany
city: Wuerzburg
country: Germany
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: