Efficacy and Safety of Belimumab in Subjects With Primary Sjögren's Syndrome

Inclusion Criteria:

• Have a diagnosis of primary SS according to the updated American European ConsensusGroup Criteria. In addition, patients must be always positive for anti-SSA or anti-SSBantibodies

• Have the presence, at screening, of Systemic involvement (polysynovitis, skin, renal,lung, CNS involvement, peripheral neuropathy, vasculitis, autoimmune cytopenia,defined in Annex 1) or persistent (up to 2 months) parotid, submandibular or lachrymalgland swelling of more than 2 cm OR Objective sicca (positive oral and/or ocular tests reported in the American EuropeanConsensus Group Criteria) with at least one among the following biological features ofserum B lymphocyte activation : increased IgG levels increased free light chain levels of immunoglobulins (according tocentral laboratory ranges) increased serum beta2-microglobulin levels decreased C4 levels (C4 levels inferior to central laboratory ranges) monoclonal gammapathy cryoglobulinemia OR

• SS of more recent onset, i.e., less than 5 years of duration of symptoms, associatedwith:

• oral or ocular dryness

• fatigue

• musculoskeletal pain (i.e, 3 criteria for response as reported at page (ix-x),characterized by VAS score more than 50/100 in all the 3 fields.

Exclusion Criteria:

1. Any BLyS-targeted (BLyS-receptor fusion protein [BR3], TACI Fc, or belimumab) at anytime.

2. Any of the following within 364 days of Day 0:

• B-cell targeted therapy (eg, rituximab, other anti-CD20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab]

• A biologic investigational agent other than B cell targeted therapy (eg, abetimussodium, anti CD40L antibody [BG9588/ IDEC 131]).

4- Intravenous or oral cyclophosphamide within 180 days of Day 0.

5- Any of the following within 90 days of Day 0:

• Anti-TNF therapy

• Interleukin-1 receptor antagonist

• Abatacept

• Interleukin-6 receptor antagonist

• Intravenous immunoglobulin

• Prednisone > 100 mg/day

• Plasmapheresis.

9- Very severe SS disease.

10- Major organ or hematopoietic stem cell/marrow transplant.

11- Unstable or uncontrolled acute or chronic diseases not due to SS

13- History of malignant neoplasm within the last 5 years, except for adequatelytreated cancers of the skin (basal or squamous cell) or carcinoma in situ of theuterine cervix.

14- Required management of acute or chronic infections, as follows:

• Currently on any suppressive therapy for a chronic infection

• Hospitalization for treatment of infection within 60 days of Day 0.

• Use of parenteral (IV or IM) antibiotics

16- Historically or at screening positive test for HIV antibody, hepatitis C virusantibodies, or, hepatitis B surface antigen (HbsAg) (with or without positive serumHBV DNA), or antiHBcAg positivity (without anti-HbsAg positivity).

17- Grade 3 or greater laboratory abnormality based on the protocol toxicity scaleexcept for the following that are allowed:

• Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment.

• Stable Grade 3/4 proteinuria (≤ 6 g/24 hour equivalent by spot urine protein tocreatinine ratio allowed). (mentioned earlier in Exclusion #8)

• Stable Grade 3 neutropenia or stable Grade 3 white blood cell count.