Clinical trial NCT00299104: A Study to Evaluate Rituximab in Combination With Methotrexate in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
Official title: A Randomized, Phase 3, Controlled, Double-Blind, Parallel-Group, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate (MTX) Compared to MTX Alone, in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rituxan
MTX
RA
IMAGE
WA17047
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2006-03-06
Enrollment: 755
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase III, randomized, controlled, double-blind, parallel group, international study in approximately 750 patients with active Rheumatoid Arthritis (RA) who are naive to Methotrexate (MTX) therapy. Rheumatoid Factor (RF)-positive and RF-negative patients will be enrolled and will be allocated equally between 3 treatment arms.


Eligibility criteria: Inclusion criteria:

* Adult patients 18-80 years of age
* RA for ≥ 2 months;
* Receiving outpatient treatment
* Patients naive to, and considered to be candidates for, methotrexate treatment

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 rheumatoid arthritis, or RA before the age of 16
* Surgery within 12 weeks of study
* Previous treatment with any approved or investigational biologic agent for RA, an anti-alpha4-integrin antibody or co-stimulation modulator, or cell-depleting therapy
* Concurrent treatment with any biologic agent or DMARD other than methotrexate

Primary outcomes:
measure: Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52
timeFrame: Baseline and week 52
Secondary outcomes:
measure: Change From Baseline in Modified Sharp Erosion Score at Week 52
timeFrame: Baseline and week 52
measure: Percentage of Patients Without Radiographic Progression at Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Patients Without Radiographic Progression in Total Erosion Score at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 52
timeFrame: Baseline and week 52
measure: Change From Baseline in the Modified Total Sharp Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in the Total Erosion Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants Without Radiographic Progression at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52
timeFrame: Week 52
measure: Change From Baseline in the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Participants With American College of Rheumatology (ACR) ACR70 Response at Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Participants With DAS28-ESR Remission at Week 52
timeFrame: Week 52
measure: Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Week 52
timeFrame: Baseline, Week 52
measure: The Percentage of Participants With Major Clinical Response at Week 52
timeFrame: Week 52
measure: Percentage of Participants With DAS28-ESR Low Disease Activity at Week 52
timeFrame: Week 52
measure: Percentage of Participants With American College of Rheumatology (ACR) ACR20 Response at Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Participants With American College of Rheumatology (ACR) ACR90 Response at Week 52
timeFrame: Baseline, Week 52
measure: Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in the SF-36 Physical Health Component Summary Score at Week 52 and Week 104
timeFrame: Baseline, Week 52, Week 104
measure: Change From Baseline in the SF-36 Mental Health Component Summary Score at Week 52 and Week 104
timeFrame: Baseline, Weeks 52, Week 104
measure: Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Physical Health Component Score at Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Mental Health Component Score at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in the Modified Total Sharp Score at Week 104
timeFrame: Baseline, Week 104
measure: Change From Baseline in the Total Erosion Score at Week 104
timeFrame: Baseline, Week 104
measure: Percentage of Participants Without Radiographic Progression at Week 104
timeFrame: Baseline, Week 104
measure: Percentage of Participants Without Radiographic Progression in the Total Erosion Score at Week 104
timeFrame: Week 104
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 104
timeFrame: Baseline, Week 104
Other outcomes:
Locations:
Study officials:
affiliation: Genentech, Inc.
name: Arndt Schottelius, M.D.
role: STUDY_DIRECTOR
References:
citation: Tak PP, Rigby W, Rubbert-Roth A, Peterfy C, van Vollenhoven RF, Stohl W, Healy E, Hessey E, Reynard M, Shaw T. Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE. Ann Rheum Dis. 2012 Mar;71(3):351-7. doi: 10.1136/annrheumdis-2011-200170. Epub 2011 Oct 19.
citation: Rigby W, Ferraccioli G, Greenwald M, Zazueta-Montiel B, Fleischmann R, Wassenberg S, Ogale S, Armstrong G, Jahreis A, Burke L, Mela C, Chen A. Effect of rituximab on physical function and quality of life in patients with rheumatoid arthritis previously untreated with methotrexate. Arthritis Care Res (Hoboken). 2011 May;63(5):711-20. doi: 10.1002/acr.20419.
citation: Tak PP, Rigby WF, Rubbert-Roth A, Peterfy CG, van Vollenhoven RF, Stohl W, Hessey E, Chen A, Tyrrell H, Shaw TM; IMAGE Investigators. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011 Jan;70(1):39-46. doi: 10.1136/ard.2010.137703. Epub 2010 Oct 11.