Randomized, Double-Blind, Placebo-Controlled, Multicenter, Exploratory Phase II Study to Compare Three Dose Regimens of GLPG0259 vs Placebo, in Combination with Methotrexate, Administered for 12 Weeks to Subjects with Active Rheumatoid Arthritis and an Inadequate Response to Methotrexate

1) 18-70 years of age on the day of signing informed consent
2) Fulfill the 1987 revised ACR criteria for the classification of RA, but must not be wheelchair or bed bound ( functional class IV)
3.Have active RA as shown by five or more swollen joints (from the 66-joint count), five or more tender joints (from 68-joint count), and a serum C-reactive protein (CRP) >=1.5 mg/dL;
4.Have received methotrexate for six months or longer and at a stable dose of 7.5 to 25 mg/week for >=12 weeks prior to screening and willing to continue on this regimen for the duration of the study;
5.If taking oral steroids, these should be at a dose <=10 mg/day of prednisone or prednisone equivalent and stable for at least four weeks prior to screening;
6.If taking non-steroidal anti-inflammatory drugs (NSAIDs), these must be at a stable dose for at least two weeks prior to screening;
7.The results of the following laboratory tests performed at the central laboratory at screening must be within the limits specified below:
a. Hemoglobin >=8.5 g/dL (International System of Units [SI]: >=85 g/L);
b. White blood cells >=3.0 x 103 cells/mm3 (SI: >=3.0 x109 cells/L);
c. Neutrophils >=1.5 x 103 cells/mm3 (SI: >=1.5 x109 cells/L);
d. Platelets >=100 x 103 cells/mm3 (SI: >=100 x109 cells/L);
e. Serum ALT and aspartate aminotransferase (AST) <=1.5 x ULN;
f. Total bilirubin level <=1.25 x ULN; and
8.Female subjects must have a negative pregnancy test unless they are surgically sterile or have been post-menopausal for at least one year (12 consecutive months without menses);
9.Women of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for at least 12 weeks after the last dose of study drug. Women who have had a complete surgical hysterectomy or are postmenopausal are exempt from this requirement. Medically acceptable forms of birth control include oral contraceptives, injectable or implantable methods, intrauterine devices, tubal ligation (if performed more than one year before screening), or double barrier contraception. Sexually active men must agree to use a medically acceptable form of contraception during the study and continue its use for at least 12 weeks after the last dose of study drug; and
10.Able and willing to sign the informed consent prior to screening evaluations and agree to schedule of assessments.

1. Treatment with DMARDs other than background methotrexate, including oral or injectable gold,sulfasalazine, hydroxychloroquine, azathioprine, or D penicillamine within four weeks prior to screening, cyclosporine within eight weeks prior to screening, and leflunomide within three months prior to screening;
2.Current or previous RA treatment with a biological agent, with the exception of biologics administered in a clinical study setting more than six months prior to screening (12 months for rituximab or other B cell depleting agents);
3.Previous treatment at any time with a cytotoxic agent, other than methotrexate, before screening. These agents include, but are not limited to, chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents;
4.Receipt of an intra-articular or parenteral corticosteroid injection within four weeks prior to screening;
5.Current regular use of aspirin or any other anti-coagulant medication;
6.Known hypersensitivity to study drug ingredients or a significant allergic reaction to any drug as determined by the Investigator, such as anaphylaxis, requiring hospitalization;
7.Positive serology for human immunodeficiency virus (HIV)1 or 2 or hepatitis B or C, or any history of HIV or hepatitis from any cause with the exception of hepatitis A;
8.History of any inflammatory rheumatological disorders other than RA;
9.Have undergone surgical treatments for RA including synovectomy and arthroplasty within three months prior to screening and/or a joint surgery is planned within the next months;
10.Symptoms of clinically significant illness other than RA (including but not limited to cardiopulmonary, renal, metabolic, hematologic, or psychiatric disorders) within three months prior to screening;
11.History of active infections requiring intravenous antibiotics within the past four weeks;
12.History of malignancy within the past five years (except for basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been treated with no evidence of recurrence);
13.History of tuberculosis (TB) infection as determined by:
a.a positive diagnostic TB test result (defined as a positive QuantiFERON TB Gold test), and
b.a chest radiograph (both posterior-anterior and lateral views), taken within three months prior to screening and read by a qualified radiologist, with evidence of current active TB or old inactive TB.
14.Administration of a live vaccine within four weeks prior to screening;
15.Participation in any investigational drug/device clinical study within four weeks prior to screening, in biological agents clinical studies within six months prior to screening, and B cell-depleting agent clinical studies within 12 months prior to screening;
16.History within the previous two years or current evidence of drug or alcohol abuse;
17.Pregnant or lactating women; and
18.Any condition or circumstances which in the opinion of the Investigator may make a subject unlikely or unable to complete the study or comply with study procedures and requirements, or may pose a risk to the subject*s safety.