Oral CF101 Tablets and Methotrexate Treatment in Rheumatoid Arthritis Patients

Inclusion Criteria:

• Males and females ages 18-75 years

• Meet the criteria of the American College of Rheumatology for RA (Arnett FC et al.Arthritis Rheum 1988;31:315-324; refer to Appendix 1. diagnostic criteria forRheumatoid Arthritis)

• 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 either: (c) Westergren ESR of >=28mm/hour; OR (d) CRP level above the upper limit of normal for the central referencelaboratory

• Treatment with weekly oral or parenteral methotrexate for >=6 months prior to baseline

• Methotrexate route of administration has been unchanged for >=2 months prior tobaseline

• Dose of methotrexate has been stable at 15-25 mg/week for >=2 months, and is expectedto remain stable throughout the study; the stable dose of methotrexate mayalternatively be 10-12.5 mg/week if documented toxicity has precluded a higher dose

• If taking hydroxychloroquine or chloroquine, administration duration has been for >=3months and dose has been stable for >=2 months prior to baseline

• If taking a nonsteroidal anti-inflammatory agent (NSAID), dose has been stable for atleast 1 month prior to baseline, and will remain unchanged during protocolparticipation

• If taking an oral corticosteroid, dose is <10 mg/day prednisone or equivalent, hasbeen stable for at least 1 month prior to the stabilization period, and will remainstable through the stabilization and entire treatment and follow-up period

• Negative screening serum pregnancy test for female patients of childbearing potential

• Females of childbearing potential must utilize, throughout the course of the trial, 2methods of contraception deemed adequate by the Investigator (for example, oralcontraceptive pills plus a barrier method)

Exclusion Criteria:

• Receipt of any of the following for at least a 1 month stabilization period prior todosing: 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 priorto dosing

• Receipt of leflunomide for at least a 2 month period prior to screening, unlesspatient 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

• Participation in a previous trial CF101 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, thestabilization period vChange in hydroxychloroquine or chloroquine dose level duringthe 2 months prior to, or during, the stabilization period

• Receipt of parenteral or intra-articular corticosteroids during the 1 month prior to,or during, the stabilization period

• Significant cardiac arrhythmia or conduction block, congestive heart failure, or anyother evidence of clinically significant heart disease; other clinically significantfindings on screening electrocardiogram (ECG)

• Hemoglobin level <9.0 gm/dL at the screening visit

• Platelet count <125,000/mm3 at the screening visit

• White blood cell count <3000/mm3 at the screening visit

• Serum creatinine level outside the central laboratory's normal limits at the screeningvisit

• Liver aminotransferase (ALT and/or AST) levels greater than 1.25 times the centrallaboratory's upper limit of normal at the screening visit

• Significant acute or chronic medical or psychiatric illness that, in the judgment ofthe Investigator, could compromise patient safety, limit the patient's ability tocomplete the study, and/or compromise the objectives of the study