Tolerance and Efficacy of Rituximab in Sjogren's Disease

Last updated: February 4, 2025
Sponsor: University Hospital, Brest
Overall Status: Completed

Phase

2/3

Condition

Dermatomyositis (Connective Tissue Disease)

Sjogren's Syndrome

Treatment

Rituximab (mabthera) Injection

Placebo: NaCl 0.9% or Glucose 5%

Clinical Study ID

NCT00740948
TEARS
  • Ages 18-80
  • All Genders

Study 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

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • 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 evaluatedglobal scores of the disease (activity of the disease including extra glandularmanifestations), pain, sicca syndrome and fatigue over the last week.

  • Rheumatoid factor or anti 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,

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

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, hepatitisB or C, HIV, tuberculosis, severe diabetes or any other chronic disease or evidenceof infection,

  • if they have had severe allergic or anaphylactic reactions to humanized or murinemonoclonal antibodies

  • or if they are unable to understand the protocol.

  • Other : neutrophil count < 1.5 x 103/L, live/attenuated vaccine within 28 days priorto baseline, pregnancy, breast feeding,

Study Design

Total Participants: 122
Treatment Group(s): 2
Primary Treatment: Rituximab (mabthera) Injection
Phase: 2/3
Study Start date:
March 01, 2008
Estimated Completion Date:
January 31, 2013

Study 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,

Connect with a study center

  • CHU Avicenne

    Bobigny,
    France

    Site Not Available

  • CHU de Brest

    Brest, 29200
    France

    Site Not Available

  • CHU Clermont-Ferrand

    Clermont-ferrand, 63003
    France

    Site Not Available

  • GH Le Havre

    Le Havre, 76 083
    France

    Site Not Available

  • AP-HP Bicêtre

    Le KREMLIN-BICETRE, 94275
    France

    Site Not Available

  • Ch Le Mans

    Le Mans, 72 037
    France

    Site Not Available

  • CHRU de LILLE

    Lille, 59 037
    France

    Site Not Available

  • CHU de Marseille

    Marseille,
    France

    Site Not Available

  • Hopital LAPEYRONIE

    Montpellier, 34 295
    France

    Site Not Available

  • CHU de Nantes

    Nantes, 44 093
    France

    Site Not Available

  • CHU Bichat

    Paris, 75018
    France

    Site Not Available

  • Hôpital Cochin APHP

    Paris, 75 679
    France

    Site Not Available

  • Hôpital SUD CHU Rennes

    Rennes, 35 203
    France

    Site Not Available

  • CHU Rouen

    Rouen, 76 031
    France

    Site Not Available

  • CHU de Strasbourg

    Strasbourg, 67 200
    France

    Site Not Available

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