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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

This study has been completed.
Sponsor:
Collaborator:
Biogen
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00468546
First received: April 30, 2007
Last updated: September 1, 2015
Last verified: September 2015
  Purpose
This study will assess the safety and efficacy of rituximab combined with MTX in participants with active RA who have had an inadequate response to anti-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.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: MabThera/Rituxan
Drug: Methotrexate
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-controlled, Double-blind, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Alpha Therapies

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With American College of Rheumatology 20 (ACR20) Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants With an ACR50 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Percentage of Participants With ACR70 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change from Baseline in Disease Activity Score of 28 Joints (DAS28) at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Percentage of Participants With DAS28 Low Disease Activity and DAS28 Remission at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change from Baseline in the ACR Core Set (SJC, TJC, Participant's and Physician's Global Assessments, Health Assessment Questionnaire [HAQ], Pain, C-Reactive Protein [CRP], and Erythrocye Sedimentation Rate [ESR]) Scores at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change From Baseline of Short Form 36 (SF-36) Total Scores at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change From Baseline in the Physical and Mental Component Scores of SF-36 at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change From Baseline in the Genant-modified Sharp Total Score at Weeks 24, 56, and 104 [ Time Frame: Weeks 24, 56 and 104 ] [ Designated as safety issue: No ]
  • Change From Baseline in the Genant-modified Sharp Erosion Score at Weeks 24, 56, and 104 [ Time Frame: Weeks 24, 56, and 104 ] [ Designated as safety issue: No ]
  • Change From Baseline in the Genant-modified Sharp Joint Space Narrowing Score at Weeks 24, 56, and 104 [ Time Frame: Weeks 24, 56, and 104 ] [ Designated as safety issue: No ]

Enrollment: 522
Study Start Date: July 2003
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Plus Methotrexate
Placebo will be administered by intravenous infusion on Days 1 and 15.
Drug: Methotrexate
2
Other: Placebo
3
Experimental: Rituximab plus Methotrexate
Rituximab 1000 milligrams (mg) will be administered by intravenous infusion on Days 1 and 15.
Drug: MabThera/Rituxan
1
Drug: Methotrexate
2

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00468546

  Show 115 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Biogen
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00468546     History of Changes
Other Study ID Numbers: WA17042  102-20 
Study First Received: April 30, 2007
Last Updated: September 1, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Rituximab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 26, 2016