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

NCT ID: NCT00468546

Last Updated: 2016-10-25

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

520 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-05-31

Study Completion Date

2012-07-31

Brief Summary

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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.

Detailed Description

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Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Study Groups

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Placebo Plus Methotrexate

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.

Group Type PLACEBO_COMPARATOR

Methotrexate

Intervention Type DRUG

2

Placebo

Intervention Type OTHER

3

Rituximab plus Methotrexate

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.

Group Type EXPERIMENTAL

MabThera/Rituxan

Intervention Type DRUG

1

Methotrexate

Intervention Type DRUG

2

Interventions

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MabThera/Rituxan

1

Intervention Type DRUG

Methotrexate

2

Intervention Type DRUG

Placebo

3

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biogen

INDUSTRY

Sponsor Role collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_CHAIR

Hoffmann-La Roche

Locations

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Birmingham, Alabama, United States

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Mesa, Arizona, United States

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Paradise Valley, Arizona, United States

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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Fullerton, California, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Palo Alto, California, United States

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Pasadena, California, United States

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Rancho Mirage, California, United States

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Santa Maria, California, United States

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Upland, California, United States

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Danbury, Connecticut, United States

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Boca Raton, Florida, United States

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Delray Beach, Florida, United States

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Fort Lauderdale, Florida, United States

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Jupiter, Florida, United States

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Largo, Florida, United States

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Orlando, Florida, United States

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Boise, Idaho, United States

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Coeur d'Alene, Idaho, United States

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Meridian, Idaho, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Indianapolis, Indiana, United States

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Shreverport, Louisiana, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Kalamazoo, Michigan, United States

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Lansing, Michigan, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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St Louis, Missouri, United States

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Albany, New York, United States

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Manhasset, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Smithtown, New York, United States

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Chapel Hill, North Carolina, United States

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Durham, North Carolina, United States

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Greenville, North Carolina, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Dayton, Ohio, United States

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Mayfield, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Duncansville, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Amarillo, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Waco, Texas, United States

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Salt Lake City, Utah, United States

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Burlington, Vermont, United States

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Seattle, Washington, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Madison, Wisconsin, United States

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Madison, Wisconsin, United States

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Brussels, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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Liège, , Belgium

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Hamilton, Ontario, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Le Kremlin-Bicêtre, , France

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Montpellier, , France

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Paris, , France

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Rouen, , France

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Strasbourg, , France

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Toulouse, , France

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Tours, , France

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Berlin, , Germany

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Dresden, , Germany

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Leipzig, , Germany

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Ratingen, , Germany

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Würzburg, , Germany

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Cork, , Ireland

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Dublin, , Ireland

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Haifa, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Udine, Friuli Venezia Giulia, Italy

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Arenzano, Liguria, Italy

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Genoa, Liguria, Italy

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Brescia, Lombardy, Italy

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Milan, Lombardy, Italy

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Pisa, Tuscany, Italy

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Amsterdam, , Netherlands

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Drammen, , Norway

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Lillehammer, , Norway

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Oslo, , Norway

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Tromsø, , Norway

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Cannock, , United Kingdom

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Leeds, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Metropolitan Borough of Wirral, , United Kingdom

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Newcastle upon Tyne, , United Kingdom

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Countries

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United States Belgium Canada France Germany Ireland Israel Italy Netherlands Norway United Kingdom

References

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Lal P, Su Z, Holweg CT, Silverman GJ, Schwartzman S, Kelman A, Read S, Spaniolo G, Monroe JG, Behrens TW, Townsend MJ. Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment. Arthritis Rheum. 2011 Dec;63(12):3681-91. doi: 10.1002/art.30596.

Reference Type DERIVED
PMID: 22127691 (View on PubMed)

Keystone E, Burmester GR, Furie R, Loveless JE, Emery P, Kremer J, Tak PP, Broder MS, Yu E, Cravets M, Magrini F, Jost F. Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti-tumor necrosis factor therapy. Arthritis Rheum. 2008 Jun 15;59(6):785-93. doi: 10.1002/art.23715.

Reference Type DERIVED
PMID: 18512710 (View on PubMed)

Other Identifiers

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102-20

Identifier Type: OTHER

Identifier Source: secondary_id

WA17042

Identifier Type: -

Identifier Source: org_study_id

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