Oral CF101 and Methotrexate Treatment in Rheumatoid Arthritis Patients

Inclusion Criteria: * Males and females ages 18-75 years * Meet the criteria of the American Rheumatism Association for RA (Arnett FC et al. Arthritis Rheum 1988;31:315-324, Appendix 1) * Not bed- or wheelchair-bound * Active RA, as indicated by the presence of (a) \>=6 swollen joints (28 joint count); AND (b) \>=6 tender joints (28 joint count); AND at least one of the following: (c) Westergren ESR of \>=28 mm/hour; OR (d) CRP level above the upper limit of normal for the central reference laboratory; OR (e) morning stiffness for \>=45 minutes * Treatment with weekly oral or parenteral methotrexate for \>=6 months prior to baseline * Methotrexate route of administration has been unchanged for \>=2 months prior to baseline * Dose of methotrexate has been stable at 15-25 mg/week for \>=2 months, and is expected to remain stable throughout the study; the stable dose of methotrexate may alternatively be 10-12.5 mg/week if documented toxicity has precluded a higher dose * If taking hydroxychloroquine, administration duration has been \>=3 months and dose has been stable for \>=2 months prior to baseline * If taking a nonsteroidal anti-inflammatory agent (NSAID), dose has been stable for at least 1 month prior to baseline, and will remain unchanged during protocol participation * If taking an oral corticosteroid, dose is \<=10 mg/day prednisone or equivalent, has been stable for at least 1 month prior to the washout period, and will remain stable through the washout and entire treatment and follow-up period * Absence of clinically significant findings, such as interstitial pneumonitis or active pulmonary infection, on chest X-ray taken within 6 months prior to screening Exclusion Criteria: * Receipt of any of the following for at least a 1 month washout period prior to dosing: sulfasalazine, oral or injectable gold, azathioprine, minocycline, penicillamine, anakinra * Receipt of etanercept for at least a 6 week period prior to dosing * Receipt of cyclosporine, infliximab or adalimumab for at least a 2 month period prior to dosing * Receipt of leflunomide for at least a 2 month period prior to screening, unless patient has undergone cholestyramine washout at least 1 month prior to dosing * Receipt of cyclophosphamide for at least a 6 month period prior to dosing * Receipt of rituximab at any previous time * Receipt of CF101 in a previous trial * Use of oral corticosteroids \>10 mg of prednisone, or equivalent, per day * Change in NSAID dose level for 1 month prior to dosing * Change in oral corticosteroid dose level during the 1 month prior to, or during, the washout period * Change in hydroxychloroquine dose level during the 2 months prior to, or during, the washout period * Receipt of parenteral or intra-articular corticosteroids during the 1 month prior to, or during, the washout period * Presence or history of uncontrolled asthma * Presence or history of uncontrolled arterial hypertension or symptomatic hypotension * Significant cardiac arrhythmia or conduction block, congestive heart failure, or any other evidence of clinically significant heart disease; other clinically significant findings on screening electrocardiogram (ECG) * Hemoglobin level \<9.0 gm/L * Platelet count \<125,000/mm3 * White blood cell count \<3000/mm3 * Serum creatinine level outside the laboratory's normal limits * Liver aminotransferase levels greater than 1.2 times the laboratory's upper limit of normal * Known or suspected immunodeficiency or human immunodeficiency virus positivity * Pregnancy, lactation, or inadequate contraception as judged by the Investigator