efficacy and safety of belimumab in subjects with primary sjögren's syndrome

Conditions: Sjögren's Syndrome

Summary: sjögren's syndrome (ss) is a systemic autoimmune disease characterized by an increase in baff (blys) levels and a resulting b cell hyperactivity. b cells are involved in the pathogenesis of ss in both systemic and glandular features, and b cell downregulation may lead to a decrease of disease activity. moreover, pathogenesis of ss is closed to that of systemic lupus erythematosus, where belimumab has been proven to be effective.

sjögren's syndrome (ss) is a systemic autoimmune disease characterized by an increase in baff (blys) levels and a resulting b cell hyperactivity. b cells are involved in the pathogenesis of ss in both systemic and glandular features, and b cell downregulation may lead to a decrease of disease activity. moreover, pathogenesis of ss is closed to that of systemic lupus erythematosus, where belimumab has been proven to be effective. this phase ii open-label study has 2 mains objectives: * to evaluate the proof of concept of efficacy of belimumab in subjects with ss * to evaluate the safety and tolerability of belimumab in subjects with ss belimumab will be administered (10mg/kg on d0 d14 d28 and every 28 days for 24 weeks, with extension to 48 weeks if responders) to all patients

Eligibility criteria:
inclusion criteria: * have a diagnosis of primary ss according to the updated american european consensus group criteria. in addition, patients must be always positive for anti-ssa or anti-ssb antibodies * 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 lachrymal gland swelling of more than 2 cm or objective sicca (positive oral and/or ocular tests reported in the american european consensus group criteria) with at least one among the following biological features of serum b lymphocyte activation : increased igg levels increased free light chain levels of immunoglobulins (according to central 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, associated with: * 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 any time. 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, abetimus sodium, 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 adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine 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 virus antibodies, or, hepatitis b surface antigen (hbsag) (with or without positive serum hbv dna), or antihbcag positivity (without anti-hbsag positivity). 17- grade 3 or greater laboratory abnormality based on the protocol toxicity scale except 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 to creatinine ratio allowed). (mentioned earlier in exclusion #8) * stable grade 3 neutropenia or stable grade 3 white blood cell count.

Keywords: belimumab sjögren's syndrome sjögren disease