Oral CF101 Tablets Treatment in Patients With Rheumatoid Arthritis

A Phase IIB Study of the Efficacy and Safety of Daily CF101 in Patients With Active Rheumatoid Arthritis and Elevated Baseline Expression Levels of Peripheral Blood Mononuclear Cell A3 Adenosine Receptors

This trial will test the hypothesis that the administration of CF101, a novel anti-inflammatory agent, to patients with rheumatoid arthritis and high A3AR expression at baseline will relieve signs and symptoms of the disease.

This will be a multi-center, randomized, double-blind, parallel-group, placebo-controlled, study in which patients with active RA and high A3AR expression at baseline will be randomized to the addition of either CF101 1.0 mg or placebo given orally q12h for 12 weeks. Screening examinations will occur within 1 month prior to dosing. Washout of other disease-modifying antirheumatic drugs (DMARDs), including biological agents, will occur prior to dosing; if washout is necessary, patients must re-qualify for inclusion following the washout. Doses of nonsteroidal anti-inflammatory drugs (NSAIDS) and corticosteroids must be stable for >=1 month prior to dosing and remain so during protocol participation. Disease activity will be assessed using swollen and tender joint counts, physician and patient global assessments (by visual analog scale, VAS), patient reported pain (by VAS), a Health Assessment Questionnaire (HAQ) Disability Index (DI), Westergren erythrocyte sedimentation rate (ESR, Screening, Weeks 0 and12), and C-reactive protein (CRP) levels. Assessments will take place at Screening, Baseline (Week 0), and at Weeks 2, 4, 8, and 12.

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, 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 either: (c) Westergren ESR of >=28 mm/hour; OR (d) CRP level above the upper limit of normal for the central reference laboratory
• Elevated PBMC A3AR expression level, defined as >= 1.5-fold over a predetermined normal population standard, following the appropriate DMARD/biologic washout period (see Exclusion Criteria) but within 2 weeks of beginning dosing
• If taking a nonsteroidal anti-inflammatory agent (NSAID), dose has been stable for at least 1 month prior to the A3AR Qualification Visit, 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 A3AR Qualification Visit, and will remain unchanged during protocol participation
• In the Investigator's opinion, the ability to understand the nature of the study and any hazards of participation, and to communicate satisfactorily with the Investigator and to participate in, and to comply with, the requirements of the entire protocol
• Negative screening serum pregnancy test for female patients of childbearing potential
• Females of childbearing potential must utilize, throughout the course of the trial, 2 methods of contraception deemed adequate by the Investigator (for example, oral contraceptive pills plus a barrier method)
• All aspects of the protocol explained and written informed consent obtained

Exclusion Criteria:

• Receipt of any of the following for at least a 1 month washout period prior to the A3AR Qualification Visit: methotrexate, sulfasalazine, oral or injectable gold, azathioprine, minocycline, penicillamine, anakinra
• Receipt of etanercept for at least a 6 week washout period prior to the A3AR Qualification Visit
• Receipt of chloroquine, hydroxychloroquine, cyclosporine, infliximab, golimumab or adalimumab for at least a 2 month washout period prior to the A3AR Qualification Visit
• Receipt of leflunomide for at least a 2 month washout period prior to the A3AR Qualification Visit, unless patient has undergone cholestyramine washout at least 1 month prior to testing
• Receipt of cyclophosphamide for at least a 6 month period prior to the A3AR Qualification Visit
• Receipt of rituximab at any previous time
• Previous failure to respond to methotrexate or any anti-rheumatic biological agent
• 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 the A3AR Qualification Visit
• Change in oral corticosteroid dose level during the 1 month prior to the A3AR Qualification Visit
• Receipt of parenteral or intra-articular corticosteroids during the 1 month prior to the A3AR Qualification Visit