Rituximab for the Treatment of Early Rheumatoid Arthritis (RA)

• Status: Terminated
• Trial end date: 2009-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, pain, stiffness, damage, and ultimately loss of joint function. Scientists estimate that about 1.3 million people (0.6 percent) of the U.S. adult population have RA. Current therapies target the immune system early in the disease process before joint damage occurs, and include drugs such as methotrexate (MTX) and tumor necrosis factor (TNF)-blocking agents. Rituximab is a disease-modifying antirheumatic drug (DMARD) recently approved by the FDA for use in combination with MTX for treatment of moderately to severely active RA in patients who have had an inadequate response to TNF-blocking agents, in an effort to try to slow the course of the disease. This study will examine the effects of rituximab on the immune response and disease activity in participants with early RA who have not been treated with any disease-modifying agent. In addition, the safety and tolerability of rituximab in this population will be examined.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Autoimmunity Centers of Excellence
• Treatments: Antibodies; Antibodies, Monoclonal; Immunoglobulins; Rituximab

Criteria

Inclusion Criteria:

• Diagnosis of RA, as defined by fulfilling at least four of seven American College of Rheumatology (ACR) criteria

• Positive for rheumatoid factor (RF) and/or anticyclic citrullinated peptide (CCP)

• The presence of arthritis symptoms for more than 6 weeks but less than 1 year

• Active RA, as defined by at least four swollen joints, at least four tender joints, and either an erythrocyte sedimentation rate (ESR) of greater than 30 mm/hr OR C-reactive protein level greater than 1.0 mg/dL (normal less than 0.4)

• Willing to adhere to the study requirements

• Willing to use acceptable effective forms of contraception

Exclusion Criteria:

• Allergy to methotrexate (MTX)

• Previous exposure to anti-CD20 monoclonal antibody (mAb) or other type(s) of mAb therapy

• Previous disease-modifying anti-rheumatic drugs (DMARD) therapy

• Previous use of a biologic agent

• Currently taking daily oral steroid doses of greater than 7.5 milligrams (mg)

• Receipt of intra-articular injections within 4 weeks prior to study entry

• Current peptic ulcer disease (PUD)

• Unwilling to stop drinking alcohol (ETOH)

• History of alcohol or substance abuse

• Active infection, or chronic or persistent infection that might worsen with immunosuppressive treatment (e.g., Human Immunodeficiency Virus [HIV], hepatitis B virus [HBV], hepatitis C virus [HCV], tuberculosis [TB])

• Interstitial lung disease observed by chest x-ray [chest radiograph]

• Known coronary artery disease or significant cardiac arrhythmias or severe congestive heart failure (New York Heart Association [NYHA] classes III or IV)

• Definitive diagnosis of another autoimmune rheumatologic disease (e.g., systemic lupus erythematosus [SLE], scleroderma, primary Sjögren's syndrome, primary vasculitis)

• History of immunoglobulin E (IgE)-mediated or non-IgE-mediated hypersensitivity or known anaphylaxis to mouse proteins

• History of cancer. Exception: participants with previous resected basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ Grade I cervical cancer within 5 years prior to study entry are not excluded from study eligibility

• History of positive purified protein derivative (PPD) test (i.e., positive tuberculosis [TB] test) without treatment for TB infection or chemoprophylaxis for TB exposure

• History of inflamed pancreas

• Live vaccine within 3 months of study entry

• Certain abnormal laboratory values

• Require certain medications

• Any psychiatric disorder that would prevent a participant from providing informed consent

• Any condition or treatment (including biologic therapies) that, in the opinion of the investigator, may place the participant at unacceptable risk during the study

• Pregnancy