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

Genentech

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: rituximab; Drug: methylprednisolone; Drug: folate; Drug: placebo; Drug: methotrexate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00299104

WA17047

U3373g

Details and patient eligibility

About

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.

Enrollment: 755 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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755 participants in 3 patient groups, including a placebo group

Rituximab (0.5 g x 2) + Methotrexate

Experimental group

Description:

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

Treatment:

Drug: folate

Drug: rituximab

Drug: methylprednisolone

Drug: methotrexate

Rituximab (1.0 g x 2) + Methotrexate

Experimental group

Description:

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

Treatment:

Drug: folate

Drug: rituximab

Drug: methylprednisolone

Drug: methotrexate

Placebo + Methotrexate

Placebo Comparator group

Description:

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.

Treatment:

Drug: folate

Drug: placebo

Drug: methylprednisolone

Drug: methotrexate