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

This study has been completed.
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
University Hospital, Brest
ClinicalTrials.gov Identifier:
NCT00740948
First received: August 22, 2008
Last updated: January 21, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Sjogren's Disease
Drug: Rituximab (mabthera) Injection
Drug: Placebo: NaCl 0.9% or Glucose 5%
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Tolerance and Efficacy of Rituximab in Sjogren's Disease

Resource links provided by NLM:


Further study details as provided by University Hospital, Brest:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Variations from baseline to week 24 of clinical, biological and histological data [ Time Frame: 24, 36 and 48 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 122
Study Start Date: March 2008
Study Completion Date: January 2013
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Rituximab
Drug: Rituximab (mabthera) Injection
2 * 1g of Rituximab at the 1st day and at the 14th day.
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.

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,

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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,
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00740948

Locations
France
CHU de Brest
Brest, France, 29200
CHU Clermont-Ferrand
Clermont-ferrand, France, 63003
GH Le Havre
Le Havre, France, 76 083
AP-HP Bicêtre
Le KREMLIN-BICETRE, France, 94275
Ch Le Mans
Le Mans, France, 72 037
CHRU de LILLE
Lille, France, 59 037
CHU de Marseille
Marseille, France
Hopital LAPEYRONIE
Montpellier, France, 34 295
CHU de Nantes
Nantes, France, 44 093
Hôpital Cochin APHP
Paris, France, 75 679
CHU Bichat
Paris, France, 75018
Hôpital SUD CHU Rennes
Rennes, France, 35 203
CHU Rouen
Rouen, France, 76 031
CHU de Strasbourg
Strasbourg, France, 67 200
Sponsors and Collaborators
University Hospital, Brest
Ministry of Health, France
Investigators
Principal Investigator: Alain SARAUX, Pr University Hospital, Brest
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Brest
ClinicalTrials.gov Identifier: NCT00740948     History of Changes
Other Study ID Numbers: TEARS
Study First Received: August 22, 2008
Last Updated: January 21, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority

Keywords provided by University Hospital, Brest:
Sjogren's disease
Rituximab
Treatment
anti CD20

Additional relevant MeSH terms:
Sjogren's Syndrome
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Xerostomia
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Dry Eye Syndromes
Lacrimal Apparatus Diseases
Eye Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 22, 2014