Efficacy and Safety of Belimumab in Primary Sjögren's Syndrome
Condition: Sjögren's Syndrome
MeSH terms: Sjogren's Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      Background and rationale Sjögren's syndrome (SS) is a systemic autoimmune disease
      characterized by chronic inflammation of salivary and lachrymal glands, frequently
      accompanied by systemic symptoms. The presence of various autoantibodies such as rheumatoid
      factor (RF) and anti-SSA/SSB antibodies, as well as hypergammaglobulinemia, reflect B cell
      hyperactivity. About five percent of patients with SS develop malignant B cell lymphoma,
      usually of the mucosa-associated lymphoid tissue (MALT) type and most frequently located in
      the major salivary glands. Currently, there is a lack of evidence-based intervention therapy
      which may influence SS-related chronic inflammation and lymphoproliferation. B cells are
      involved in the pathogenesis of SS, and B cell downregulation may lead to a decrease of
      disease activity. Patients with more residual exocrine gland function, e.g., those with SS of
      shorter duration, might better benefit from systemic therapy, as reported in a preliminary
      study on the efficacy of B-cell depletion in SS.This study will examine the effect of the
      drug Belimumab in patients with SS. Patients aged more than 18 years with SS may be eligible
      for this study. Candidates will be screened with complete history and physical examination,
      chest x-rays, and oral and eye examinations.
    

Detailed description: 
      A Phase 2, proof of concept, 52 Week Open Study to Evaluate the Efficacy and Safety of
      Belimumab (HGS1006, LymphoStat-B), a Fully Human Monoclonal Anti-BLyS Antibody, in Subjects
      with Sjögren's Syndrome (pSS)

      Clinical Development Phase: 2

      A total of 15 patients will be recruited

      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

      This is a Phase 2, proof of concept, 52-week open study to evaluate the efficacy and safety
      of belimumab in subjects with active SS. In addition to receiving standard stable therapy,
      subjects will receive 10 mg/kg belimumab. At week 28, if worsening any patient will exit the
      study band considered as a treatment failure.

      If the disease is stable at week 28, and if both the referent clinician and the patient agree
      in continuing the study, the study will continue up to week 52 in that patient, since a
      delayed response may occur (as shown in systemic lupus erythematosus patients treated with
      belimumab: Chathman et al. Arthritis Rheumatism 2008 ).

      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

      c) SS of more recent onset, i.e., less than 5 years of duration of symptoms, associated with:
      i) oral or ocular dryness and ii) fatigue and iii) 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.
    

Intervention name(s): LimphoStat-B
Intervention type(s): Drug
Intervention description(s): subjects will receive 10 mg/kg belimumab, in solution for infusion, monthly
Other intervention name(s): Belimumab
Intervention MeSH terms: Belimumab
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Belimumab,Sjögren's Syndrome.; Have a diagnosis of primary SS according to the updated American European Consensus Group Criteria