This is a randomized, double-blind, placebo-controlled study to determine the effectiveness of a new experimental oral agent, CGP-59830, in restoring defective B-lymphocyte function in subjects with systemic lupus erythematosus (SLE). We have completed the study for determining the effectiveness of the drug in increasing the number of B cells in the blood. There were 13 subjects randomized in the study. Twelve were evaluable for efficacy. Eleven of these subjects completed the study. One subject withdrew from the study due to an adverse event (GI upset). One of the eleven subjects was found to have a >2 fold increase in CD20+ B cells. One patient was found to have a doubling of their CD20+ B cell count in the treatment arm. There was no change in the CD20+ B cell counts in the placebo arm. The sample size of 11 patients evaluable for efficacy was too small for statistical analysis. The study was closed by the Principal Investigator, the FDA, and the IRB after 11 patients were enrolled. This is a phase II/III trial to determine the safety of CGP-59830 in patients with Systemic Lupus Erythematosus (SLE) at doses of 2.5, 5 and 10mg/day for 6 weeks. We have enrolled 11 subjects in this trial. Eight have completed the trial. The primary endpoint of the study is the safety of the drug. There have been no side effects. We have enrolled 4 subjects in the 5mg/day dose group and 4 in the 10mg/day dose group. The study was closed by the Principal Investigator due to lack of improvement. There have been 3 failures. The drug has been well tolerated with mild GI side effects in 2 subjects. Enrollment will be completed in September 2009. We are monitoring the patients closely to determine if any improvement occurs in the CD20+ B cell counts. In November 2007 we submitted a protocol for a study to determine the effectiveness of CGP-59830 in reversing B cell abnormalities in the SLE mouse model. Due to the fact that CGP-59830 is the lead drug in a class of anti-sense oligonucleotides for the treatment of SLE, this study is very important. The drug is still in early phase II trials and it is crucial that we determine if this drug has any effect on B cells in SLE. We are comparing two methods to count B cells in the blood of mice with lupus - flow cytometry and staining with antibodies to CD22, CD43, and CD45R. We are comparing several B cell subpopulations as well. The results from this study may have implications for B cell abnormalities in human SLE. We have opened a new study in collaboration with Genzyme Corporation to evaluate the effectiveness of CGP-59830 in treating patients with SLE. We have enrolled two patients so far. We are conducting safety and preliminary efficacy studies. We expect to open additional patients when available. We have developed a new collaboration to evaluate CGP-59830 in treating patients with systemic sclerosis. We have enrolled two patients in this study. We expect to open additional patients in the coming year. Two subjects in this study were previously treated with other investigational drugs for their disease (Tofacitinib and Anakinra). Both subjects failed to respond to their previous treatment. Both subjects are now being treated with CGP-59830 and have had dramatic improvement in their symptoms, as documented by the physician investigators, a physician in private practice and a rheumatologist. We have begun the phase III clinical trial for CGP-59830 in Rheumatoid Arthritis (RA) patients. We have enrolled 10 subjects so far in the trial. Four subjects have completed the study. The purpose of the study is to evaluate the effectiveness of the drug for the treatment of rheumatoid arthritis in a small sample of patients. The primary endpoint of the study is a change in tender joint counts (TJC) and a change in swollen joint counts (SJC) in the subjects in the CGP-59830 group at two weeks. We have also collected data on improvement of subjects with RA at 12 weeks and at 20 weeks. We plan to enroll up to 40 subjects in this study. We have collected data on the safety of the drug in the RA trial and no serious adverse events have been reported in these patients. We have also enrolled 3 subjects in a study to assess the effectiveness of CGP-59830 in treating patients with Crohn's Disease. The study is ongoing. We are monitoring these patients closely to determine safety and side effects. We plan to enroll 3 more patients in the study. We also have developed a new collaborative effort to evaluate CGP-59830 in treating patients with Sjogren's Syndrome. This is a phase II trial for the drug in treating patients with Sjogren's Syndrome. We have enrolled one patient in the study and she is currently being monitored for safety. Her protocol is to stay on the drug for 12 months and she will have frequent blood draws to determine safety and efficacy of the drug. We plan to enroll up to 10 subjects in the study. We plan to open another study for CGP-59830 for patients with Systemic Sclerosis. This study will evaluate the effectiveness of the drug in improving skin involvement in these patients. This is a phase II/III study and we will enroll up to 10 patients. We expect to open the study for enrollment in the next two weeks. We plan to enroll subjects with systemic sclerosis who are in early stages of the disease and who have cutaneous involvement. We are developing new studies with this agent in the treatment of other rheumatic diseases, including but not limited to giant cell arteritis, polyarticular juvenile idiopathic arthritis, antineutrophil cytoplasmic antibody-associated vasculitis, scleroderma, dermatomyositis, and mixed connective tissue disease. We have been evaluating patients with GCA in a study. We expect to complete enrollment in this study in the next two months. We will initiate two new studies. One study is evaluating the effectiveness of CGP-59830 in treating patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This is a phase II/III trial. We have started enrollment in the study and we expect to enroll up to 6 patients. We have also initiated a study to evaluate the effectiveness of CGP-59830 in treating patients with Scleroderma. We have