Tolerance and Efficacy of Rituximab in Sjogren's Disease
Condition: Sjogren's Disease
MeSH terms: Sjogren's Syndrome
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      CLINICAL PHASE II INDICATION Sjogren's syndrome RATIONALE Sjögren's syndrome (SS) is an
      autoimmune disorder affecting 0.2% to 3% of the general population. Pharmacological treatment
      can improve the sicca symptoms, often transiently, but they are unable to modify the course
      of the disease.Open label studies suggested that low-dose rituximab produced acute and
      complete CD20 depletion in blood and tissue; was well tolerated without corticosteroid use;
      and significantly improved glandular and extra-glandular manifestations of pSS. Larger
      controlled studies are now warranted. Our hypothesis is that two infusions of 1000 mg of
      Rituximab may be better than placebo to treat patients suffering from pSS. To test this
      hypothesis, we propose to compare patients with recent and/or severe pSS treated with either
      Rituximab or placebo.

      OBJECTIVES Primary objective : Evaluation of the efficacy defined as a 30% improvement
      between Day 1 and Week 24 in the values on 2 of the 4 VAS measuring global scores of the
      disease (activity of the disease including extra glandular manifestations), joint pain,
      fatigue, and the most disturbing dryness.Secondary objectives : Variations from baseline to
      week 24 of:

      The 0-100-mm VAS scores for dry mouth, dry eyes, dry trachea, dry vagina, and dry skin;
      fatigue; pain; Tender and swollen joint counts; Tender points; Other systemic manifestation;
      Unstimulated salivary flow rate; Schirmer and van Bijsterveld scores (2-3); C-reactive
      protein (CRP) and erythrocyte sedimentation rate (ESR); rheumatoid factor (RF); ANA; serum
      IgG, IgA, and IgM; complement; cryoglobulinemia; and counts of B and T cells; Evaluation of
      the safety of Rituximab during the study Evaluation of the improvement evaluated on VAS by
      the physician Evaluation of the disease activity scores as suggested by Bowman and Vitali
      Evaluation of Chisholm score, B cells characteristics and DNA microarray on labial accessory
      salivary gland (SG) biopsy samples, and salivary gland echography at inclusion and at week
      24.

      TRIAL DESIGN Multicenter, randomized, double-blind, placebo-controlled trial NUMBER OF
      SUBJECTS : 120
    

Detailed description: 
      TARGET POPULATION Inclusion criteria : Patients will be eligible if :

      they fulfill the new American-European Consensus Group criteria for pSS and have :

        -  a recent (less than 10 years) and active disease as assessed by :

        -  values > 50 mm on 2 of 4 visual analogue scales (VAS) (0-100mm) that evaluated global
           scores of the disease (activity of the disease including extra glandular
           manifestations), pain, sicca syndrome and fatigue over the last week.

        -  Rheumatoid factor or SSA>1.5N or cryoglobulinemia or hypergammaglobulinemia or high
           level of beta2 microglobulinemia or hypocomplémentemia.

        -  and/or at least one of the following severe signs: parotidomegaly, arthritis, purpura,
           pulmonary involvement, tubulopathy, neurological involvement, thrombocytopenia.

      Additional inclusion criteria will be as follows:

        -  informed consent

        -  age 18-80 years,

        -  stable non-steroidal anti-inflammatory drugs

        -  and no prescription of immunosuppressive agents for at least 4 weeks prior to inclusion

        -  Use of a reliable mean of contraception (for patients of reproductive potential)

      Exclusion criteria :

      Patients should be excluded if they have a secondary SS, if they received cytotoxic drugs
      during the previous 4 months, if they have severe renal or haematological failure, a history
      of cancer, hepatitis B or C, HIV, tuberculosis, severe diabetes or any other chronic disease
      or evidence of infection, if they have had severe allergic or anaphylactic reactions to
      humanized or murine monoclonal antibodies or if they are unable to understand the protocol.
      Other : neutrophil count < 1.5 x 103/L, live/attenuated vaccine within 28 days prior to
      baseline, pregnancy, breast feeding,
    

Intervention name(s): Rituximab (mabthera) Injection; Placebo: NaCl 0.9% or Glucose 5%
Intervention type(s): Drug; Drug
Intervention description(s): 2 * 1g of Rituximab at the 1st day and at the 14th day.; 2* 250ml of NaCl 0.9% or Glucose 5% at the 1st day and at the 14th day.
Intervention MeSH terms: Rituximab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Sjogren's disease; Rituximab; Treatment; anti CD20