Effect of B-cell Depletion in Patients With Primary Sjögren's Syndrome

NCT ID: NCT00426543

Last Updated: 2017-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2010-08-31

Brief Summary

The primary purpose of the study is to determine whether B-cell depletion with Rituximab has an effect on the oral, ocular and general disease manifestations in patients with primary Sjögren´s syndrome, that is, an effect on the symptoms of oral and ocular dryness, improvement of the glandular function and a beneficial effect on the general symptoms such as fatigue. The secondary purpose of the study is the investigate the underlying autoimmune and pathophysiological mechanisms in Sjögren´s syndrome.

Detailed Description

The trial is designed as a double-blind parallel comparison between 2 infusions of 1 g Rituximab and solvent (saline) given two weeks apart, in 22 patients with the diagnosis of primary Sjögren's syndrome as based on the current American-European consensus classification criteria. The patients will be followed at the Department of Oral Medicine, Clinical Oral Physiology, Oral Pathology & Anatomy, University of Copenhagen, the Department of Rheumatology, Rigshospitalet and at the Department of Ophthalmology, Rigshospitalet.

The primary endpoints are clinical and a response has been delineated as at least 50% improvement in score. With the provision that this occurs for any item in at least 60% of the treated patients as compared to 1% in the control patients, a power of over 80% at doubled sided significance level of 5% is found with 20 patients.The patients will be followed within this study for 6 months after Rituximab.

The study will allow the first real dynamic appraisal of the immunologic pathophysiology in Sjögren's syndrome. Hence attempts will be made to determine at the best possible level if and how Rituximab influences and possibly resets the autoimmunity both at the whole body and particularly at the local level in the salivary glands. Also the basal transport mechanism in salivary secretion which must necessarily be perturbed in Sjögren's syndrome will be scrutinized employing the best available of techniques. Every possible effort to envisage a priory, and then monitor, the decisive mechanisms has been made.

In particular this includes repetitive biopsies from the parotid glands, which will allow combining functional and structural data to reduce as much as possible random variability of crucial quantities. Also this will allow for the first time to assess the relative and combined utility of obtaining biopsies from both the parotid and labial salivary glands.

Roche A/S provide investigational medicine, but the study was initiated and is entirely controlled by the investigators.

Conditions

Primary Sjögren's Syndrome; Xerostomia; Hyposalivation; Keratoconjunctivitis Sicca; Fatigue

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

MabThera (rituximab)

1000 mg infusion twice with 14 days interval

Intervention Type: DRUG

Rituximab, Mabthera

1000 mg Rituximab infusion in 500 ml isotonic sodiumchloride twice with 14 days interval

Intervention Type: DRUG

Other Intervention Names

Mabthera

Eligibility Criteria

Inclusion Criteria

• Female patients fulfilling the current American-European consensus classification criteria.
• Fertile-age female patients must use safe anticonceptional methods such as pills, mini-pills, or intrauterine spiral.
• The fertile-age females included in the study must not get pregnant in at least 12 months after the last treatment with Rituximab.

Exclusion Criteria

• Pregnancy and lactation.
• Fertile-age females who do not use safe anticonceptional methods.
• Patients in systemic treatment with cytostatics.
• Patients who previously have been treated with Rituximab.
• Patient with an active infection that requires antibiotic treatment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Rigshospitalet, Denmark

OTHER

Sponsor Role: collaborator

University of Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Anne Marie Lynge Pedersen

Associate Professor, PhD, DDS

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anne Marie Lynge Pedersen, PhD, DDS

Role: PRINCIPAL_INVESTIGATOR

Institute of Odontology, Faculty of Health Sciences, University of Copenhagen

Locations

Institute of Odontology, Faculty of Health Sciences, University of Copenhagen

Copenhagen, , Denmark

Countries

Denmark

References

Ring T, Kallenbach M, Praetorius J, Nielsen S, Melgaard B. Successful treatment of a patient with primary Sjogren's syndrome with Rituximab. Clin Rheumatol. 2006 Nov;25(6):891-4. doi: 10.1007/s10067-005-0086-0. Epub 2005 Nov 8.

Reference Type: BACKGROUND

PMID: 16283417 (View on PubMed)

Other Identifiers

EudractCT-no. 2005-004740-31

Identifier Type: -

Identifier Source: secondary_id

KF 02 282294

Identifier Type: -

Identifier Source: org_study_id