Repeat Dose Subcutaneous Rhumatoid Arthritis Efficacy Study

A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Subjects with a history of significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis, or Felty’s syndrome) 2. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening; current or chronic history of liver disease. 3. The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. 4. A positive test for HIV antibody or risk factors which predispose subject to HIV infection. 5. A positive test for syphilis according to local guidelines. 6. History of regular alcohol consumption within 6 months of the study defined as:

• an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine. 7. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, five half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) or planning to take any investigational drug within six months of the last dose of study drug 8. The subject is currently receiving or has received an anti-rheumatic biological therapy within the following specified periods prior to dosing: Within four weeks:
• Glucocorticoid unless given in doses equivalent to <=10 mg of prednisolone/day
• Intramuscular. or i.v. corticosteroids
• Live/attenuated vaccinations
• Cyclosporine
• Etanercept
• Anakinra Within eight weeks:
• Infliximab
• Rituximab
• Abatacept 9. Previous or current exposure to biologic cell-depleting anti-rheumatic therapies, including investigational compounds (e.g. anti-CD11a, anti-CD-20, anti-CD22, anti-BLyS/BAFF, anti-CD3, anti-CD5, anti-CD52). 10. Previous or current exposure to adalimumab. 11. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 12. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. 13. Where participation in the study would result in donation of blood or blood products in excess of 600 mL within a 56 day period. 14. Pregnant females as determined by positive (serum or urine) hCG test at screening or prior to dosing, or lactating females. 15. The subject has received immunization with a vaccine within four weeks before the first dose of study medication or requires a vaccine within 30 days after the last dose of study medication. 16. A CD4+ lymphocyte count outside the range of (0.53

1.76 × 10^9 )/L during Screening. 17. The subject has had a significant systemic infection during the 6 weeks before the first dose of study drug (e.g., infection requiring hospitalization, major surgery, or IV antibiotics to resolve); other infections, e.g., bronchitis, sinusitis, localized cellulitis, candidiasis, or urinary tract infections, must be assessed on a case-by-case basis by the investigator regarding whether they are serious enough to warrant exclusion). 18. The subject has received a course of oral antibiotics within 2 weeks of dosing day one. 19. History of recurrent or chronic infection. 20. The subject has had a splenectomy. 21. Subjects with a screening chest X-ray suggestive of TB without documentation of adequate TB treatment will be excluded. Screening for latent TB infection using intradermal injection of tuberculin (e.g. the Mantoux test or equivalent) should be conducted in accordance with local guidelines. The tuberculin skin test results should be evaluated according to the criteria for immunocompromised subjects. Subjects with a positive skin tuberculin test should be excluded if the investigator judges the patient to be at risk of latent TB infection). Cohort 6 are required to undergo radiographic screening with CXR, this is optional according to local guidelines for all other cohorts. 22. The subject has undergone any major surgical procedure within the 8 weeks before signing the consent form, or planning to undergo any such surgery within the 3 months after the last dose of study drug. 23. Positive plasma / white cell JC virus (JCV) PCR (either compartment) 24. The subject has a condition or situation that, in the investigator’s judgment, is likely to cause the subject to be unable or unwilling to participate in study procedures or to complete all scheduled assessments. 25. Predisposition to thromboembolic disease, or thromboembolic event (excluding superficial) in past 12 months. 26. Has clinically significant cardiovascular and/or cerebrovascular disease, including but not limited to:

• Previous history of stroke or transient ischaemic attack
• Active unstable coronary artery disease within the last 6 months
• Documented myocardial infarction in the 1 year prior to screening
• Any cardiac surgery including percutaneous transluminal coronary angioplasty, coronary artery bypass grafting within a year prior to screening
• Unstable angina
• Clinically significant arrhythmia or valvular heart disease within previous year
• Congestive heart failure with New York Heart Association Class II to IV symptoms. Class I is acceptable.
• Untreated hypertension with systolic pressure greater than 160mmHg, and/or diastolic pressure greater than 95 mmHg. 27. The subject has clinically significant abnormal laboratory values during the Screening period, other than those due to RA. Abnormal values are permitted if, upon re-test, the abnormality was resolved 28. Liver Function Tests must not be outside the range: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2x upper limit of normal (ULN); alkaline phosphatase and bilirubin ≤ 1.5x ULN (isolated bilirubin > 1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%).