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.

Hoffmann-La Roche0 sites378 target enrollmentFebruary 2006

ConditionsRheumatoid Arthritis

Interventionsrituximab [MabThera/Rituxan]

Drugsrituximab [MabThera/Rituxan]

Overview

Phase: Phase 3
Intervention: rituximab [MabThera/Rituxan]
Conditions: Rheumatoid Arthritis
Sponsor: Hoffmann-La Roche
Enrollment: 378
Primary Endpoint: Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20)
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

February 2006

End Date

March 2013

Last Updated

11 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

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.

Arms & Interventions

1

Intervention: rituximab [MabThera/Rituxan]

2

Intervention: rituximab [MabThera/Rituxan]

3

Intervention: rituximab [MabThera/Rituxan]

Outcomes

Primary Outcomes

Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20)

Time Frame: Week 48

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

Secondary Outcomes

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