Clinical trial NCT00422383: A Study of Retreatment With MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis (RA)
Official 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2007-01-17
Enrollment: 378
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20)
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With ACR 50% Improvement Criteria (ACR50) Response at Week 48
timeFrame: Week 48
measure: Percentage of Participants With a ACR 70% Improvement Criteria (ACR70) Response at Week 48
timeFrame: Week 48
measure: Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR): Adjusted Mean Change From BL at Week 48
timeFrame: BL, Week 48
measure: Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category
timeFrame: Week 48
measure: Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48
timeFrame: BL, Week 48
measure: Short-Form 36 Health Survey (SF-36) Score
timeFrame: BL, Week (Wk) 24 and 48
measure: Change in SF-36 Score From BL
timeFrame: BL, Weeks 24 and 48
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)
timeFrame: 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).
measure: Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL
timeFrame: 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).
measure: Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days
timeFrame: 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).
measure: Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL)
timeFrame: BL
measure: Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN)
timeFrame: BL, Days 1 and 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Peripheral CD20+ B Cell Count in Cells/µL
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Peripheral CD22+ B Cell Count in Cells/µL
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Peripheral CD19+CD27+ B Cell Count in Cells/µL
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Peripheral CD3+ T Cell Count in Cells/µL
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Change From BL in Peripheral CD3+ T Cell Count
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Peripheral CD4+ T Cell Count in Cells/µL
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Change From BL in Peripheral CD4+ T Cell Count
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Peripheral CD8+ T Cell Count in Cells/µL
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Change From BL in Peripheral CD8+ Cell Count
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Change From BL in Peripheral CD16+56+ Cell Count
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN
timeFrame: BL, Weeks 24 and 48
measure: Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative
timeFrame: BL, Weeks 8, 24, and 48
measure: Anti-Cyclic Citrullinated Peptide (CCP) Antibody Titers at BL in Units Per mL (U/mL)
timeFrame: BL
measure: Change From BL in Anti-CCP Antibody Titers in U/mL
timeFrame: Weeks 8, 24, and 48
measure: Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Change From BL in Complement C3 Protein Level in g/L
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Change From BL in Complement C4 Protein Level in g/L
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L
timeFrame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
measure: Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers
timeFrame: BL, Weeks 24 and 48
measure: Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers
timeFrame: BL, Weeks 24 and 48
measure: Percentage of Participants With Positive Recall Antigen Antibody Titers
timeFrame: BL, Weeks 24 and 48
Other outcomes:
Locations:
city: Coffs Harbour
country: Australia
state: New South Wales
city: Sydney
country: Australia
state: New South Wales
city: Maroochydore
country: Australia
state: Queensland
city: Southport
country: Australia
state: Queensland
city: Malvern
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Gent
country: Belgium
city: Goiania
country: Brazil
state: GO
city: Sao Paulo
country: Brazil
state: SP
city: Penticton
country: Canada
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: London
country: Canada
state: Ontario
city: Newmarket
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Trois-rivieres
country: Canada
state: Quebec
city: Beijing
country: China
city: Beijing
country: China
city: Oulu
country: Finland
city: Bois Guillaume
country: France
city: Bordeaux
country: France
city: Dijon
country: France
city: Le Mans
country: France
city: Lille
country: France
city: Montpellier
country: France
city: Nice
country: France
city: Paris
country: France
city: Bad Nauheim
country: Germany
city: Hamburg
country: Germany
city: Heidelberg
country: Germany
city: Herne
country: Germany
city: Köln
country: Germany
city: Osnabrück
country: Germany
city: Ratingen
country: Germany
city: Debrecen
country: Hungary
city: Eger
country: Hungary
city: Coppito
country: Italy
state: Abruzzo
city: Potenza
country: Italy
state: Basilicata
city: Ferrara
country: Italy
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
state: Emilia-Romagna
city: Arenzano
country: Italy
state: Liguria
city: Genova
country: Italy
state: Liguria
city: Pieve Di Coriano
country: Italy
state: Lombardia
city: Torino
country: Italy
state: Piemonte
city: Palermo
country: Italy
state: Sicilia
city: Pisa
country: Italy
state: Toscana
city: Prato
country: Italy
state: Toscana
city: Siena
country: Italy
state: Toscana
city: Valeggio sul Mincio
country: Italy
state: Veneto
city: Amsterdam
country: Netherlands
city: Leiden
country: Netherlands
city: Nijmegen
country: Netherlands
city: Auckland City
country: New Zealand
city: Christchurch
country: New Zealand
city: Timaru
country: New Zealand
city: Kosice
country: Slovakia
city: Piestany
country: Slovakia
city: Piestany
country: Slovakia
city: Cape Town
country: South Africa
city: Diepkloof
country: South Africa
city: Pretoria
country: South Africa
city: Gijon
country: Spain
state: Asturias
city: Barcelona
country: Spain
city: Burgos
country: Spain
city: Leon
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Taoyuan
country: Taiwan
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Khon Kaen
country: Thailand
city: Barnsley
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Londonderry
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Middlesborough
country: United Kingdom
city: Northampton
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Reading
country: United Kingdom
city: Truro
country: United Kingdom
city: Wigan
country: United Kingdom
city: Wirral
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
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.