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