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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00422383




Registration number
NCT00422383
Ethics application status
Date submitted
15/01/2007
Date registered
17/01/2007
Date last updated
4/05/2015

Titles & IDs
Public title
A Study of Retreatment With MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis (RA)
Scientific title
A Randomized, Double-blind Study to Evaluate the Effect of Various Re-treatment Regimens of MabThera in Combination With Methotrexate on Treatment Response in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate.
Secondary ID [1] 0 0
WA17044
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - rituximab [MabThera/Rituxan]
Treatment: Drugs - rituximab [MabThera/Rituxan]
Treatment: Drugs - rituximab [MabThera/Rituxan]

Experimental: 1 -

Experimental: 2 -

Experimental: 3 -


Treatment: Drugs: rituximab [MabThera/Rituxan]
500mg iv in days 1 and 15, and 500mg iv on days 168 and 182

Treatment: Drugs: rituximab [MabThera/Rituxan]
500mg iv on days 1 and 15, and 1000mg iv on days 168 and 182

Treatment: Drugs: rituximab [MabThera/Rituxan]
1000mg iv on days 1 and 15 and 1000mg iv (or placebo in UK)on days 168 and 182
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20)
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Percentage of Participants With ACR 50% Improvement Criteria (ACR50) Response at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Percentage of Participants With a ACR 70% Improvement Criteria (ACR70) Response at Week 48
Timepoint [2] 0 0
Week 48
Secondary outcome [3] 0 0
Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR): Adjusted Mean Change From BL at Week 48
Timepoint [3] 0 0
BL, Week 48
Secondary outcome [4] 0 0
Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category
Timepoint [4] 0 0
Week 48
Secondary outcome [5] 0 0
Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48
Timepoint [5] 0 0
BL, Week 48
Secondary outcome [6] 0 0
Short-Form 36 Health Survey (SF-36) Score
Timepoint [6] 0 0
BL, Week (Wk) 24 and 48
Secondary outcome [7] 0 0
Change in SF-36 Score From BL
Timepoint [7] 0 0
BL, Weeks 24 and 48
Secondary outcome [8] 0 0
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)
Timepoint [8] 0 0
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).
Secondary outcome [9] 0 0
Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL
Timepoint [9] 0 0
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).
Secondary outcome [10] 0 0
Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days
Timepoint [10] 0 0
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).
Secondary outcome [11] 0 0
Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL)
Timepoint [11] 0 0
BL
Secondary outcome [12] 0 0
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN)
Timepoint [12] 0 0
BL, Days 1 and 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [13] 0 0
Peripheral CD20+ B Cell Count in Cells/µL
Timepoint [13] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [14] 0 0
Peripheral CD22+ B Cell Count in Cells/µL
Timepoint [14] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [15] 0 0
Peripheral CD19+CD27+ B Cell Count in Cells/µL
Timepoint [15] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [16] 0 0
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL
Timepoint [16] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [17] 0 0
Peripheral CD3+ T Cell Count in Cells/µL
Timepoint [17] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [18] 0 0
Change From BL in Peripheral CD3+ T Cell Count
Timepoint [18] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [19] 0 0
Peripheral CD4+ T Cell Count in Cells/µL
Timepoint [19] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [20] 0 0
Change From BL in Peripheral CD4+ T Cell Count
Timepoint [20] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [21] 0 0
Peripheral CD8+ T Cell Count in Cells/µL
Timepoint [21] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [22] 0 0
Change From BL in Peripheral CD8+ Cell Count
Timepoint [22] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [23] 0 0
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL
Timepoint [23] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [24] 0 0
Change From BL in Peripheral CD16+56+ Cell Count
Timepoint [24] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [25] 0 0
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN
Timepoint [25] 0 0
BL, Weeks 24 and 48
Secondary outcome [26] 0 0
Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative
Timepoint [26] 0 0
BL, Weeks 8, 24, and 48
Secondary outcome [27] 0 0
Anti-Cyclic Citrullinated Peptide (CCP) Antibody Titers at BL in Units Per mL (U/mL)
Timepoint [27] 0 0
BL
Secondary outcome [28] 0 0
Change From BL in Anti-CCP Antibody Titers in U/mL
Timepoint [28] 0 0
Weeks 8, 24, and 48
Secondary outcome [29] 0 0
Percentage of Participants With Complement Component 3 (C3) Protein Level = LLN
Timepoint [29] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [30] 0 0
Change From BL in Complement C3 Protein Level in g/L
Timepoint [30] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [31] 0 0
Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L
Timepoint [31] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [32] 0 0
Percentage of Participants With Complement Component 4 (C4) Protein Level = LLN
Timepoint [32] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [33] 0 0
Change From BL in Complement C4 Protein Level in g/L
Timepoint [33] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [34] 0 0
Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L
Timepoint [34] 0 0
BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Secondary outcome [35] 0 0
Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers
Timepoint [35] 0 0
BL, Weeks 24 and 48
Secondary outcome [36] 0 0
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers
Timepoint [36] 0 0
BL, Weeks 24 and 48
Secondary outcome [37] 0 0
Percentage of Participants With Positive Recall Antigen Antibody Titers
Timepoint [37] 0 0
BL, Weeks 24 and 48

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2013
Sample size
Target
Accrual to date
Final
378
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
- Coffs Harbour
Recruitment hospital [2] 0 0
- Sydney
Recruitment hospital [3] 0 0
- Maroochydore
Recruitment hospital [4] 0 0
- Southport
Recruitment hospital [5] 0 0
- Malvern
Recruitment hospital [6] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [2] 0 0
2145 - Sydney
Recruitment postcode(s) [3] 0 0
4558 - Maroochydore
Recruitment postcode(s) [4] 0 0
4215 - Southport
Recruitment postcode(s) [5] 0 0
3144 - Malvern
Recruitment postcode(s) [6] 0 0
3168 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Gent
Country [2] 0 0
Brazil
State/province [2] 0 0
GO
Country [3] 0 0
Brazil
State/province [3] 0 0
SP
Country [4] 0 0
Canada
State/province [4] 0 0
British Columbia
Country [5] 0 0
Canada
State/province [5] 0 0
Manitoba
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
China
State/province [8] 0 0
Beijing
Country [9] 0 0
Finland
State/province [9] 0 0
Oulu
Country [10] 0 0
France
State/province [10] 0 0
Bois Guillaume
Country [11] 0 0
France
State/province [11] 0 0
Bordeaux
Country [12] 0 0
France
State/province [12] 0 0
Dijon
Country [13] 0 0
France
State/province [13] 0 0
Le Mans
Country [14] 0 0
France
State/province [14] 0 0
Lille
Country [15] 0 0
France
State/province [15] 0 0
Montpellier
Country [16] 0 0
France
State/province [16] 0 0
Nice
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
Germany
State/province [18] 0 0
Bad Nauheim
Country [19] 0 0
Germany
State/province [19] 0 0
Hamburg
Country [20] 0 0
Germany
State/province [20] 0 0
Heidelberg
Country [21] 0 0
Germany
State/province [21] 0 0
Herne
Country [22] 0 0
Germany
State/province [22] 0 0
Köln
Country [23] 0 0
Germany
State/province [23] 0 0
Osnabrück
Country [24] 0 0
Germany
State/province [24] 0 0
Ratingen
Country [25] 0 0
Hungary
State/province [25] 0 0
Debrecen
Country [26] 0 0
Hungary
State/province [26] 0 0
Eger
Country [27] 0 0
Italy
State/province [27] 0 0
Abruzzo
Country [28] 0 0
Italy
State/province [28] 0 0
Basilicata
Country [29] 0 0
Italy
State/province [29] 0 0
Emilia-Romagna
Country [30] 0 0
Italy
State/province [30] 0 0
Liguria
Country [31] 0 0
Italy
State/province [31] 0 0
Lombardia
Country [32] 0 0
Italy
State/province [32] 0 0
Piemonte
Country [33] 0 0
Italy
State/province [33] 0 0
Sicilia
Country [34] 0 0
Italy
State/province [34] 0 0
Toscana
Country [35] 0 0
Italy
State/province [35] 0 0
Veneto
Country [36] 0 0
Netherlands
State/province [36] 0 0
Amsterdam
Country [37] 0 0
Netherlands
State/province [37] 0 0
Leiden
Country [38] 0 0
Netherlands
State/province [38] 0 0
Nijmegen
Country [39] 0 0
New Zealand
State/province [39] 0 0
Auckland City
Country [40] 0 0
New Zealand
State/province [40] 0 0
Christchurch
Country [41] 0 0
New Zealand
State/province [41] 0 0
Timaru
Country [42] 0 0
Slovakia
State/province [42] 0 0
Kosice
Country [43] 0 0
Slovakia
State/province [43] 0 0
Piestany
Country [44] 0 0
South Africa
State/province [44] 0 0
Cape Town
Country [45] 0 0
South Africa
State/province [45] 0 0
Diepkloof
Country [46] 0 0
South Africa
State/province [46] 0 0
Pretoria
Country [47] 0 0
Spain
State/province [47] 0 0
Asturias
Country [48] 0 0
Spain
State/province [48] 0 0
Barcelona
Country [49] 0 0
Spain
State/province [49] 0 0
Burgos
Country [50] 0 0
Spain
State/province [50] 0 0
Leon
Country [51] 0 0
Spain
State/province [51] 0 0
Madrid
Country [52] 0 0
Spain
State/province [52] 0 0
Sevilla
Country [53] 0 0
Taiwan
State/province [53] 0 0
Kaohsiung
Country [54] 0 0
Taiwan
State/province [54] 0 0
Taichung
Country [55] 0 0
Taiwan
State/province [55] 0 0
Taoyuan
Country [56] 0 0
Thailand
State/province [56] 0 0
Bangkok
Country [57] 0 0
Thailand
State/province [57] 0 0
Chiang Mai
Country [58] 0 0
Thailand
State/province [58] 0 0
Khon Kaen
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Barnsley
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Birmingham
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Cambridge
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Glasgow
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Londonderry
Country [64] 0 0
United Kingdom
State/province [64] 0 0
London
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Manchester
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Middlesborough
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Northampton
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Nottingham
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Reading
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Truro
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Wigan
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00422383
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00422383