Tolerance and Efficacy of Rituximab in Sjogren's Disease

NCT00740948 | Completed Phase 2 DMC

• 1 other identifier: TEARS
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 14

Brief 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

Conditions

Sjogren's Disease

Keywords

Sjogren's disease; Rituximab; Treatment; anti CD20

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Variations from baseline to week 24 of clinical, biological and histological data

  24, 36 and 48 weeks

Study Arms (2)

1

EXPERIMENTAL

Rituximab

Drug: Rituximab (mabthera) Injection

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo: NaCl 0.9% or Glucose 5%

Interventions

Rituximab (mabthera) Injection DRUG

2 \* 1g of Rituximab at the 1st day and at the 14th day.

1

Placebo: NaCl 0.9% or Glucose 5% DRUG

2\* 250ml of NaCl 0.9% or Glucose 5% at the 1st day and at the 14th day.

2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify 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 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,

You may not qualify if:

• 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,

Sponsors & Collaborators

• University Hospital, Brest: lead
• Ministry of Health, France: collaborator

Study Sites (14)

CHU de Brest

Brest, 29200, France

Location

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

GH Le Havre

Le Havre, 76 083, France

Location

AP-HP Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

Ch Le Mans

Le Mans, 72 037, France

Location

CHRU de LILLE

Lille, 59 037, France

Location

CHU de Marseille

Marseille, France

Location

Hopital LAPEYRONIE

Montpellier, 34 295, France

Location

CHU de Nantes

Nantes, 44 093, France

Location

Hôpital Cochin APHP

Paris, 75 679, France

Location

CHU Bichat

Paris, 75018, France

Location

Hôpital SUD CHU Rennes

Rennes, 35 203, France

Location

CHU Rouen

Rouen, 76 031, France

Location

CHU de Strasbourg

Strasbourg, 67 200, France

Location

Related Publications (5)

• Devauchelle-Pensec V, Pennec Y, Morvan J, Pers JO, Daridon C, Jousse-Joulin S, Roudaut A, Jamin C, Renaudineau Y, Roue IQ, Cochener B, Youinou P, Saraux A. Improvement of Sjogren's syndrome after two infusions of rituximab (anti-CD20). Arthritis Rheum. 2007 Mar 15;57(2):310-7. doi: 10.1002/art.22536.

  PMID: 17330280 BACKGROUND

• Cornec D, Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, Berthelot JM, Perdriger A, Puechal X, Le Guern V, Sibilia J, Gottenberg JE, Chiche L, Hachulla E, Yves Hatron P, Goeb V, Hayem G, Morel J, Zarnitsky C, Dubost JJ, Saliou P, Pers JO, Seror R, Saraux A. Severe Health-Related Quality of Life Impairment in Active Primary Sjogren's Syndrome and Patient-Reported Outcomes: Data From a Large Therapeutic Trial. Arthritis Care Res (Hoboken). 2017 Apr;69(4):528-535. doi: 10.1002/acr.22974.

  PMID: 27390310 DERIVED

• Costa S, Schutz S, Cornec D, Uguen A, Quintin-Roue I, Lesourd A, Berthelot JM, Hachulla E, Hatron PY, Goeb V, Vittecoq O, Pers JO, Marcorelles P, Saraux A, Devauchelle-Pensec V. B-cell and T-cell quantification in minor salivary glands in primary Sjogren's syndrome: development and validation of a pixel-based digital procedure. Arthritis Res Ther. 2016 Jan 20;18:21. doi: 10.1186/s13075-016-0924-2.

  PMID: 26785742 DERIVED

• Jousse-Joulin S, Devauchelle-Pensec V, Cornec D, Marhadour T, Bressollette L, Gestin S, Pers JO, Nowak E, Saraux A. Brief Report: Ultrasonographic Assessment of Salivary Gland Response to Rituximab in Primary Sjogren's Syndrome. Arthritis Rheumatol. 2015 Jun;67(6):1623-8. doi: 10.1002/art.39088.

  PMID: 25708147 DERIVED

• Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, Berthelot JM, Perdriger A, Puechal X, Le Guern V, Sibilia J, Gottenberg JE, Chiche L, Hachulla E, Hatron PY, Goeb V, Hayem G, Morel J, Zarnitsky C, Dubost JJ, Pers JO, Nowak E, Saraux A. Treatment of primary Sjogren syndrome with rituximab: a randomized trial. Ann Intern Med. 2014 Feb 18;160(4):233-42. doi: 10.7326/M13-1085.

  PMID: 24727841 DERIVED

MeSH Terms

Conditions

Sjogren's Syndrome

Interventions

Rituximab; Injections

Condition Hierarchy (Ancestors)

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; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Alain SARAUX, Pr

  University Hospital, Brest

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2008
• First Posted: August 25, 2008
• Study Start: March 1, 2008
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2013
• Last Updated: February 5, 2025

Record last verified: 2025-02

Locations

FR (14)