A Study to Evaluate the Safety and Efficacy of MabThera (Rituximab) in Combination With Methotrexate (MTX) in Participants With Active Rheumatoid Arthritis Who Failed on Anti-Tumor Necrosis Factor Alpha Therapy

Roche

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Other: Placebo; Drug: Methotrexate; Drug: MabThera/Rituxan

Study type: Interventional

Funder types: Industry

Identifiers

NCT00468546

102-20 (Other Identifier)

WA17042

Details and patient eligibility

About

This study will assess the safety and efficacy of rituximab combined with MTX in participants with active rheumatoid arthritis (RA) who have had an inadequate response to anti-Tumor Necrosis (TNF) alpha therapy. The anticipated time in the study is up to 2 years and the target sample size is 500 participants. Eligible participants may receive re-treatment with rituximab under a separate protocol WA17531.

Enrollment: 520 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult participants 18-80 years of age with active RA for at least 6 months;
• Received treatment for RA on an outpatient basis and experienced an inadequate response or intolerance to treatment with at least 1 anti-TNF alpha therapy (etanercept, infliximab or adalimumab);
• Must have received MTX for a minimum of 12 weeks, with the last 4 weeks, prior to screening at a stable dose;
• Participants with swollen joint count (SJC) and tender joint count (TJC) of at least 8 joints at screening and at randomization;
• Radiographic evidence of at least 1 joint with a definite erosion due to RA;
• Participants of reproductive potential must be using reliable contraceptive methods.

Exclusion criteria

• Bone or joint surgery within 8 weeks prior to screening or joint surgery planned within 24 weeks of randomization;
• Class IV functional status of RA;
• Previous treatment within 6 months with intravenous gamma globulin, or the Prosorba column;
• Intraarticular or parenteral corticosteroids within 4 weeks prior to screening visit;
• With a live vaccine within 4 weeks prior to randomization;
• Previous treatment with rituximab or other cell-depleting therapies;
• Concurrent treatment with any disease-modifying anti-rheumatic drug (except for MTX) or any anti-TNF alfa factor or other biologic therapy;
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies;
• Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders;
• Known contraindications to receiving rituximab;
• Known active bacterial, viral, fungal, mycobacterial or other infection;
• History of recurrent significant infection or history of recurrent bacterial infections;
• Primary or secondary immunodeficiency (history of, or currently active);
• History of cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that have been excised and cured);
• Women who are pregnant or breast-feeding;
• History of alcohol, drug or chemical abuse within 6 months prior to screening;
• Neuropathies and neurovasculopathies which might interfere with pain evaluation;
• Participants with poor peripheral venous access;
• Intolerance or contraindications to oral or intravenous corticosteroids.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

520 participants in 2 patient groups, including a placebo group

Placebo Plus Methotrexate

Placebo Comparator group

Description:

Participants will be administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg per os (p.o.) or parenterally once a week up to 24 weeks and will be followed up to Week 104.

Treatment:

Drug: Methotrexate

Other: Placebo

Rituximab plus Methotrexate

Experimental group

Description:

Participants will be administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and will be followed up to Week 104.

Treatment:

Drug: Methotrexate

Drug: MabThera/Rituxan