Tolerance and Efficacy of Rituximab in Sjogren's Disease - Full Text View

Sponsors and Collaborators:	University Hospital, Brest Ministry of Health, France
Information provided by:	University Hospital, Brest
ClinicalTrials.gov Identifier:	NCT00740948

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 II Phase III

MedlinePlus related topics: Salivary Gland Disorders Sjogren's Syndrome

Drug Information available for: Rituximab Dextrose

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Tolerance and Efficacy of Rituximab in Sjogren's Disease

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 ]

Estimated Enrollment:	120
Study Start Date:	March 2008
Estimated Study Completion Date:	March 2010
Estimated Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Rituximab	Drug: Rituximab (mabthera) Injection 2 * 1g of Rituximab at the 1st day and at the 14th day.
2: Placebo Comparator 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 18-50 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,

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

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

Contacts

Contact: ALAIN SARAUX, MD, PhD

33 2 98 34 72 67

alain.saraux@chu-brest.fr

Locations

France
CHU de Brest	Recruiting
Brest, France, 29200
Contact: Alain SARAUX, Pr 0033 2 98 34 72 70
Contact: Valérie DEVAUCHELLE, Dr 0033 2 98 34 72 62
Principal Investigator: Alain SARAUX, Pr
Sub-Investigator: Valérie DEVAUCHELLE, Dr
CHU Clermont-Ferrand	Recruiting
CLERMONT-FERRAND, France, 63003
Contact: Jean-Jacques DUBOST, Dr 0033 4 73 75 14 88
Principal Investigator: Jean-Jacques DUBOST, Dr
Sub-Investigator: SOUBRIER, Dr
GH Le Havre	Recruiting
Le Havre, France, 76 083
Contact: Charles ZARNITSKY, Dr 0033 2 32 73 33 78
Principal Investigator: Charles ZARNITSKY, Dr
Sub-Investigator: Didier ALCAIX, Dr
Sub-Investigator: Nathalie LEON, Dr
Ch Le Mans	Not yet recruiting
Le Mans, France, 72 037
Contact: Xavier PUECHAL, Dr 00332 43 43 26 56
Principal Investigator: Xavier PUECHAL, Dr
Sub-Investigator: Emmanuelle DERNIS, Dr
CHRU de LILLE	Recruiting
Lille, France, 59 037
Contact: Eric HACHULLA, Pr 0033 3 20 44 50 48
Principal Investigator: Eric HACHULLA, Pr
Sub-Investigator: Pierre-Yves HATRON, Pr
Sub-Investigator: David LAUNAY, Dr
Sub-Investigator: Marc LAMBERT, Dr
Hopital LAPEYRONIE	Recruiting
Montpellier, France, 34 295
Contact: Jacques MOREL, Dr 0033 4 67 33 86 39
Principal Investigator: Jacques MOREL, Dr
CHU de Strasbourg	Recruiting
Strasbourg, France, 67 200
Contact: Jean SIBILIA, Pr 0033 3 88 12 71 40
Principal Investigator: Jean SIBILIA, Pr
Sub-Investigator: Emmanuel CHATELUS, Dr
Sub-Investigator: Christelle SORDET, Dr
Hôpital Cochin APHP	Recruiting
Paris, France, 75 679
Contact: Loïc GUILLEVIN, Pr 0033 1 58 41 13 21
Principal Investigator: Loïc GUILLEVIN, Pr
Sub-Investigator: Véronique LE GUERN, Dr
Sub-Investigator: Christian PAGNOUX, Dr
AP-HP Bicêtre	Recruiting
Le KREMLIN-BICETRE, France, 94275
Contact: Xavier MARIETTE, Pr 0033 1 45 21 37 58
Principal Investigator: Xavier MARIETTE, Pr
Sub-Investigator: Jacques-Eric GOTTENBERG, Dr
Sub-Investigator: Frédéric DESMOULINS, Dr
Sub-Investigator: Stephan PAVY, Dr
Hôpital SUD CHU Rennes	Recruiting
Rennes, France, 35 203
Contact: Aleth PERDRIGER, Pr 0033 2 99 26 71 40
Principal Investigator: Aleth PERDRIGER, Pr
CHU Rouen	Recruiting
Rouen, France, 76 031
Contact: Olivier VITTCOQ, Pr 0033 2 32 88 90 19
Principal Investigator: Olivier VITTECOQ, Pr
Sub-Investigator: Vincent GOEB, Dr
Sub-Investigator: Karine LANFANT-WEYBEL, Dr
Sub-Investigator: Tassadit AIT ABDESSLAM, Dr
CHU de Nantes	Recruiting
Nantes, France, 44 093
Contact: Jean-Marie BERTHELOT, Dr 0033 2 40 08 33 41
Principal Investigator: Jean-Marie BERTHELOT, Dr
Sub-Investigator: Mohamed HAMIDOU, Pr

Sponsors and Collaborators

University Hospital, Brest

Ministry of Health, France

More Information

Publications:

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.

Responsible Party:	CHU Brest ( SARAUX/Principal Investigator )
Study ID Numbers:	TEARS
Study First Received:	August 22, 2008
Last Updated:	August 22, 2008
ClinicalTrials.gov Identifier:	NCT00740948
Health Authority:	France: Afssaps - French Health Products Safety Agency; France: French Data Protection Authority

Keywords provided by University Hospital, Brest:

Sjogren's disease
Rituximab
Treatment
anti CD20

Study placed in the following topic categories:

Mouth Diseases
Autoimmune Diseases
Rituximab
Joint Diseases
Eye Diseases
Arthritis, Rheumatoid
Lacrimal Apparatus Diseases
Dry Eye Syndromes

Rheumatic Diseases
Xerostomia
Musculoskeletal Diseases
Arthritis
Connective Tissue Diseases
Sjogren's Syndrome
Stomatognathic Diseases
Salivary Gland Diseases

Additional relevant MeSH terms:

Immunologic Factors
Immune System Diseases
Antineoplastic Agents
Therapeutic Uses

Physiological Effects of Drugs
Antirheumatic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009