Tolerance and Efficacy of Rituximab in Sjogren's Disease

Sjogren's Disease Clinical Trial

— TEARS  

Official title:

Tolerance and Efficacy of Rituximab in Sjogren's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00740948
• Other study ID #: TEARS
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: August 22, 2008
• Last updated: March 4, 2015
• Start date: March 2008
• Est. completion date: January 2013

Study information

• Verified date: March 2015
• Source: University Hospital, Brest
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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

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,

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: January 2013
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sjogren's Disease
• Sjogren's Syndrome

Intervention

Drug:
• Rituximab (mabthera) Injection
2 * 1g of Rituximab at the 1st day and at the 14th day.
• 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.

Locations

Country	Name	City	State
France	CHU de Brest	Brest
France	CHU Clermont-Ferrand	Clermont-ferrand
France	GH Le Havre	Le Havre
France	AP-HP Bicêtre	Le KREMLIN-BICETRE
France	Ch Le Mans	Le Mans
France	CHRU de LILLE	Lille
France	CHU de Marseille	Marseille
France	Hopital LAPEYRONIE	Montpellier
France	CHU de Nantes	Nantes
France	CHU Bichat	Paris
France	Hôpital Cochin APHP	Paris
France	Hôpital SUD CHU Rennes	Rennes
France	CHU Rouen	Rouen
France	CHU de Strasbourg	Strasbourg

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Brest	Ministry of Health, France

Country where clinical trial is conducted

France, 

References & Publications (1)

Devauchelle-Pensec V, Pennec Y, Morvan J, Pers JO, Daridon C, Jousse-Joulin S, Roudaut A, Jamin C, Renaudineau Y, Roué IQ, Cochener B, Youinou P, Saraux A. Improvement of Sjögren's syndrome after two infusions of rituximab (anti-CD20). Arthritis Rheum. 2007 Mar 15;57(2):310-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		24 weeks	No
Secondary	Variations from baseline to week 24 of clinical, biological and histological data		24, 36 and 48 weeks	Yes