A Study to Evaluate Rituximab in Combination With Methotrexate in Methotrexate-Naive Patients With Active Rheumatoid Arthritis

NCT ID: NCT00299104

Last Updated: 2017-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 755 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2013-07-31

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Rituximab (0.5 g x 2) + Methotrexate

Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6

Group Type: EXPERIMENTAL

folate

Intervention Type: DRUG

Intravenous repeating dose

methotrexate

Intervention Type: DRUG

Oral or parenteral repeating dose

methylprednisolone

Intervention Type: DRUG

Intravenous repeating dose

rituximab

Intervention Type: DRUG

Intravenous repeating dose

Rituximab (1.0 g x 2) + Methotrexate

Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6

Group Type: EXPERIMENTAL

folate

Intervention Type: DRUG

Intravenous repeating dose

methotrexate

Intervention Type: DRUG

Oral or parenteral repeating dose

methylprednisolone

Intervention Type: DRUG

Intravenous repeating dose

rituximab

Intervention Type: DRUG

Intravenous repeating dose

Placebo + Methotrexate

Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8.

From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.

Group Type: PLACEBO_COMPARATOR

folate

Intervention Type: DRUG

Intravenous repeating dose

methotrexate

Intervention Type: DRUG

Oral or parenteral repeating dose

methylprednisolone

Intervention Type: DRUG

Intravenous repeating dose

placebo

Intervention Type: DRUG

Intravenous repeating dose

Interventions

folate

Intravenous repeating dose

Intervention Type: DRUG

methotrexate

Oral or parenteral repeating dose

Intervention Type: DRUG

methylprednisolone

Intravenous repeating dose

Intervention Type: DRUG

placebo

Intravenous repeating dose

Intervention Type: DRUG

rituximab

Intravenous repeating dose

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arndt Schottelius, M.D.

Role: STUDY_DIRECTOR

Genentech, Inc.

References

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.

Reference Type: DERIVED

PMID: 22012969 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21557525 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20937671 (View on PubMed)

Other Identifiers

WA17047

Identifier Type: -

Identifier Source: secondary_id

U3373g

Identifier Type: -

Identifier Source: org_study_id