A Study of the Safety and Efficacy of Rituximab in Patients With Moderate to Severe Rheumatoid Arthritis Receiving Methotrexate

NCT ID: NCT00243412

Last Updated: 2011-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2009-02-28

Brief Summary

This was a Phase II, randomized, double-blind, multicenter study designed to evaluate the safety and efficacy of rituximab, administered at two different regimens for 2 years, in patients with moderate to severe active rheumatoid arthritis (RA) receiving stable doses of methotrexate (MTX).

Conditions

Rheumatoid Arthritis

Study Design

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

Study Groups

Arm A: 500 mg Rituximab

Rituximab: 1000 mg intravenous (IV) on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18).

Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion.

Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant).

Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).

Group Type: EXPERIMENTAL

folate

Intervention Type: DRUG

Minimum of 1 mg/day oral (or folinic acid 5 mg/week)

methotrexate

Intervention Type: DRUG

15-25 mg/week oral or parenteral (10-14 mg/week if intolerant)

methylprednisolone

Intervention Type: DRUG

100 mg intravenous (IV) prior to each rituximab infusion (For Arm B, for the Months 6 and 18 cycles, IV saline was administered prior to each placebo infusion)

Rituximab

Intervention Type: DRUG

500 mg or 1000 mg IV\*2.

Arm B: 1000 mg Rituximab

Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12.) For the Month 6 and 18 cycles, rituximab or placebo was administered.

Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion.

Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant).

Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).

Group Type: EXPERIMENTAL

folate

Intervention Type: DRUG

Minimum of 1 mg/day oral (or folinic acid 5 mg/week)

methotrexate

Intervention Type: DRUG

15-25 mg/week oral or parenteral (10-14 mg/week if intolerant)

methylprednisolone

Intervention Type: DRUG

100 mg intravenous (IV) prior to each rituximab infusion (For Arm B, for the Months 6 and 18 cycles, IV saline was administered prior to each placebo infusion)

Placebo

Intervention Type: DRUG

To maintain the blind, patients in Arm B (Rituximab 1000 mg) received placebo infusions at Months 6 and 18.

Rituximab

Intervention Type: DRUG

500 mg or 1000 mg IV\*2.

Interventions

folate

Minimum of 1 mg/day oral (or folinic acid 5 mg/week)

Intervention Type: DRUG

methotrexate

15-25 mg/week oral or parenteral (10-14 mg/week if intolerant)

Intervention Type: DRUG

methylprednisolone

100 mg intravenous (IV) prior to each rituximab infusion (For Arm B, for the Months 6 and 18 cycles, IV saline was administered prior to each placebo infusion)

Intervention Type: DRUG

Placebo

To maintain the blind, patients in Arm B (Rituximab 1000 mg) received placebo infusions at Months 6 and 18.

Intervention Type: DRUG

Rituximab

500 mg or 1000 mg IV\*2.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of RA for at least 6 months.
• Inadequate response to MTX
• Use of folate
• If female and of childbearing potential, have a negative serum pregnancy test within 8 weeks prior to first rituximab infusion

Exclusion Criteria

• Diagnosis of juvenile idiopathic arthritis (also known as juvenile rheumatoid arthritis) and/or RA before age 16
• Any surgical procedure, including bone/joint surgery or planned surgery within 8 weeks prior to screening or within 16 weeks of Week 1 (Day 1) visit
• Inflammatory arthritis other than RA (e.g., inflammatory bowel disease, systemic lupus erythematosus (SLE), or psoriatic arthritis)
• Functional Class IV as defined by the American College of Rheumatology (ACR) classification of functional status in RA
• Use of disease-modifying anti-rheumatic drugs (DMARDs) other than MTX within 4 weeks prior to randomization (8 weeks prior for infliximab, adalimumab, or leflunomide)
• Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
• Previous treatment with Tysabri<TM> (natalizumab)
• Previous treatment with rituximab
• Previous treatment with any cell-depleting therapies, including investigational agents
• Treatment with IV &-globulin or Prosorba(R) Column within the previous 6 months
• Use of intra-articular or parenteral corticosteroids within 4 weeks prior to screening visit
• Receipt of a vaccine within 4 weeks prior to Day 1 infusion
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Primary or secondary immunodeficiency (history of or active)
• Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, renal, hepatic, endocrine, gastrointestinal, or pulmonary disease, including any pulmonary or other condition that would preclude subject participation over the ensuing 2 years
• Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds)
• History of recurrent significant infection or any significant episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
• History of significant cytopenias or other bone marrow disorders
• History of cancer, including solid tumors and hematologic malignancies (except basal cell and squamous cell carcinoma of the skin that have been excised and cured)
• Pregnant or nursing (breast feeding) women
• Lack of peripheral venous access
• Chronic daily use of narcotic analgesics
• History of alcohol, drug, or chemical abuse within 6 months prior to screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Reiss, Pharm.D.

Role: STUDY_DIRECTOR

Genentech, Inc.

Other Identifiers

U3377g

Identifier Type: -

Identifier Source: org_study_id