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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00468546
• Other study ID #: WA17042
• Secondary ID: 102-20
• Status: Completed
• Phase: Phase 3
• First received: April 30, 2007
• Last updated: September 1, 2015
• Start date: July 2003
• Est. completion date: July 2011

Study information

• Verified date: September 2015
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 522
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• MabThera/Rituxan
1
• Methotrexate
2

Other:
• Placebo
3

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Biogen

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With American College of Rheumatology 20 (ACR20) Response at Week 24		Week 24	No
Secondary	Percentage of Participants With an ACR50 Response at Week 24		Week 24	No
Secondary	Percentage of Participants With ACR70 Response at Week 24		Week 24	No
Secondary	Change from Baseline in Disease Activity Score of 28 Joints (DAS28) at Week 24		Week 24	No
Secondary	Percentage of Participants With DAS28 Low Disease Activity and DAS28 Remission at Week 24		Week 24	No
Secondary	Percentage of Participants With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24		Week 24	No
Secondary	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		Week 24	No
Secondary	Change From Baseline of Short Form 36 (SF-36) Total Scores at Week 24		Week 24	No
Secondary	Change From Baseline in the Physical and Mental Component Scores of SF-36 at Week 24		Week 24	No
Secondary	Change From Baseline in the Genant-modified Sharp Total Score at Weeks 24, 56, and 104		Weeks 24, 56 and 104	No
Secondary	Change From Baseline in the Genant-modified Sharp Erosion Score at Weeks 24, 56, and 104		Weeks 24, 56, and 104	No
Secondary	Change From Baseline in the Genant-modified Sharp Joint Space Narrowing Score at Weeks 24, 56, and 104		Weeks 24, 56, and 104	No