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

NCT00468546 | Completed Phase 3 Results

• 2 other identifiers: WA17042102-20
• Study Type: interventional
• Target: 520
• Locations: 11 countries
• Sites: 115

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With American College of Rheumatology 20 Response at Week 24

  American College of Rheumatology (ACR) 20 response is defined as \>= 20% improvement (reduction) in score compared with baseline for both tender joint count (TJC)-68 joints and swollen joint count (SJC)-66 joints, as well as for 3 of the additional 5 ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) ranging from score 0 (no pain) to 100 (unbearable pain); Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS ranging score 0 (no disease activity) to 100 (maximum disease activity); Health Assessment Questionnaire (HAQ):8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do) for a total possible score of 0 (best) to 3 (worst); and acute-phase reactant, either C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR).

  Week 24

Secondary Outcomes (11)

• Number of Participants With an ACR 50 Response at Week 24

  Week 24

• Number of Participants With ACR 70 Response at Week 24

  Week 24

• Mean Change From Baseline in Disease Activity Score of 28 Joints at Week 24

  From Baseline (Day 1) to Week 24

• Percentage of Participants With DAS28 Low Disease Activity and DAS28 Remission at Week 24

  Week 24

• Number of Participants With Good, Moderate, or no European League Against Rheumatism Responses at Week 24

  Week 24

Study Arms (2)

Placebo Plus Methotrexate

PLACEBO COMPARATOR

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.

Drug: Methotrexate; Other: Placebo

Rituximab plus Methotrexate

EXPERIMENTAL

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.

Drug: MabThera/Rituxan; Drug: Methotrexate

Interventions

MabThera/Rituxan DRUG

1

Rituximab plus Methotrexate

Methotrexate DRUG

2

Placebo Plus Methotrexate; Rituximab plus Methotrexate

Placebo OTHER

3

Placebo Plus Methotrexate

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Biogen: collaborator

Study Sites (115)

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Birmingham, Alabama, 35294, United States

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Mesa, Arizona, 85208, United States

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Paradise Valley, Arizona, 85253, United States

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Tucson, Arizona, 85724, United States

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Little Rock, Arkansas, 72205, United States

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Fullerton, California, 92835, United States

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La Jolla, California, 92037, United States

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Los Angeles, California, 90045, United States

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Los Angeles, California, 90048, United States

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Palo Alto, California, 94304, United States

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Pasadena, California, 91105, United States

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Rancho Mirage, California, 92270, United States

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Santa Maria, California, 93454, United States

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Upland, California, 91786, United States

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Danbury, Connecticut, 06810, United States

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Boca Raton, Florida, 33486, United States

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Delray Beach, Florida, 33484, United States

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Fort Lauderdale, Florida, 33334, United States

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Jupiter, Florida, 33458, United States

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Largo, Florida, 33773, United States

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Orlando, Florida, 32806, United States

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Boise, Idaho, 83702, United States

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Coeur d'Alene, Idaho, 83814, United States

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Meridian, Idaho, 83642, United States

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Chicago, Illinois, 60612, United States

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Chicago, Illinois, 60637, United States

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Indianapolis, Indiana, 46202-5149, United States

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Indianapolis, Indiana, 46260, United States

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Shreverport, Louisiana, 71103, United States

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Baltimore, Maryland, 21224, United States

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Boston, Massachusetts, 02215, United States

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Kalamazoo, Michigan, 49048, United States

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Lansing, Michigan, 48910, United States

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Rochester, Minnesota, 55905, United States

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St Louis, Missouri, 63110, United States

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St Louis, Missouri, 63141, United States

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Albany, New York, 12206, United States

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Manhasset, New York, 11030, United States

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New York, New York, 10003, United States

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Rochester, New York, 14618, United States

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Smithtown, New York, 11787, United States

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Chapel Hill, North Carolina, 27599-7600, United States

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Durham, North Carolina, 27710, United States

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Greenville, North Carolina, 27834, United States

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Cincinnati, Ohio, 45267-0563, United States

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Cleveland, Ohio, 44195, United States

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Dayton, Ohio, 45402, United States

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Mayfield, Ohio, 44143, United States

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Oklahoma City, Oklahoma, 73103, United States

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Oklahoma City, Oklahoma, 73109, United States

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Tulsa, Oklahoma, 74135, United States

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Duncansville, Pennsylvania, 16635, United States

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Philadelphia, Pennsylvania, 19140, United States

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Philadelphia, Pennsylvania, 19141, United States

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Philadelphia, Pennsylvania, 19152, United States

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Amarillo, Texas, 79124, United States

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Dallas, Texas, 75231, United States

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Dallas, Texas, 75246, United States

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Houston, Texas, 77074, United States

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Waco, Texas, 76708, United States

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Salt Lake City, Utah, 84132, United States

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Burlington, Vermont, 05401, United States

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Seattle, Washington, 98101, United States

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Seattle, Washington, 98104, United States

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Spokane, Washington, 99204, United States

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Madison, Wisconsin, 53717, United States

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Madison, Wisconsin, 53792, United States

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Brussels, 1070, Belgium

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Liège, 4000, Belgium

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Calgary, Alberta, T2N 4Z6, Canada

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Edmonton, Alberta, T6G 2S2, Canada

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Vancouver, British Columbia, V5Z 1L7, Canada

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Hamilton, Ontario, L8N 2B6, Canada

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London, Ontario, N6A 4V2, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5G 1X5, Canada

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Le Kremlin-Bicêtre, 94275, France

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Montpellier, 34295, France

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Paris, 75679, France

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Rouen, 76031, France

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Strasbourg, 67098, France

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Toulouse, 31059, France

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Tours, 37044, France

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Berlin, 10117, Germany

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Dresden, 01067, Germany

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Leipzig, 04103, Germany

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Ratingen, 40882, Germany

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Würzburg, 97080, Germany

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Cork, Ireland

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Dublin, 4, Ireland

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Haifa, 3109601, Israel

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Haifa, 3339419, Israel

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Jerusalem, 9112001, Israel

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Petah Tikva, 4941492, Israel

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Ramat Gan, 5262000, Israel

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Tel Aviv, 6423906, Israel

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Udine, Friuli Venezia Giulia, 33100, Italy

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Arenzano, Liguria, 16011, Italy

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Genoa, Liguria, 16132, Italy

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Brescia, Lombardy, 25123, Italy

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Milan, Lombardy, 20157, Italy

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Pisa, Tuscany, 56100, Italy

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Amsterdam, 1105 AZ, Netherlands

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Drammen, 3004, Norway

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Lillehammer, 2609, Norway

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Oslo, 0370, Norway

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Tromsø, 9038, Norway

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Cannock, WS11 5XY, United Kingdom

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Leeds, LS7 4SA, United Kingdom

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London, E11 1NR, United Kingdom

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Manchester, M41 5SL, United Kingdom

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Metropolitan Borough of Wirral, CH49 5PE, United Kingdom

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Newcastle upon Tyne, NE7 7DN, United Kingdom

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Related Publications (2)

• 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.

  PMID: 22127691 DERIVED

• 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.

  PMID: 18512710 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Roche Trial Information Hotline
• Organization: F. Hoffmann-La Roche AG

global.trial_information@roche.com

+41 616878333

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2007
• First Posted: May 2, 2007
• Study Start: May 1, 2003
• Primary Completion: January 1, 2005
• Study Completion: July 1, 2012
• Last Updated: October 25, 2016
• Results First Posted: October 25, 2016

Record last verified: 2016-08

Locations

CA (7); NO (4); IL (6); GB (6); FR (7); IT (6); IE (2); BE (4); NL (1); US (67); DE (5)