Tolerance and Efficacy of Rituximab in Sjogren's Disease (TEARS)

February 4, 2025 updated by: University Hospital, Brest

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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,

Study Type

Interventional

Enrollment (Actual)

122

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Brest, France, 29200
        • CHU de Brest
      • Clermont-ferrand, France, 63003
        • CHU Clermont-Ferrand
      • Le Havre, France, 76 083
        • Gh Le Havre
      • Le KREMLIN-BICETRE, France, 94275
        • AP-HP Bicêtre
      • Le Mans, France, 72 037
        • CH Le mans
      • Lille, France, 59 037
        • Chru De Lille
      • Marseille, France
        • CHU de Marseille
      • Montpellier, France, 34 295
        • Hopital Lapeyronie
      • Nantes, France, 44 093
        • CHU de Nantes
      • Paris, France, 75018
        • CHU Bichat
      • Paris, France, 75 679
        • Hôpital Cochin APHP
      • Rennes, France, 35 203
        • Hôpital SUD CHU Rennes
      • Rouen, France, 76 031
        • CHU Rouen
      • Strasbourg, France, 67 200
        • CHU de Strasbourg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 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 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 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,

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 2
Placebo
Drug: Placebo: NaCl 0.9% or Glucose 5%
2* 250ml of NaCl 0.9% or Glucose 5% at the 1st day and at the 14th day.
Experimental: 1
Rituximab
Drug: Rituximab (mabthera) Injection
2 * 1g of Rituximab at the 1st day and at the 14th day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
30% improvement between in the values on 2 of the 4 VAS measuring global scores of the disease (activity of the disease), joint pain, fatigue, and dryness.
Time Frame: 24 weeks
24 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Variations from baseline to week 24 of clinical, biological and histological data
Time Frame: 24, 36 and 48 weeks
24, 36 and 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Brest

Collaborators

Ministry of Health, France

Investigators

  • Principal Investigator: Alain SARAUX, Pr, University Hospital, Brest

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

August 22, 2008

First Submitted That Met QC Criteria

August 22, 2008

First Posted (Estimated)

August 25, 2008

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 4, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TEARS

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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