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

March 11, 2017 updated by: Anne Marie Lynge Pedersen, University of Copenhagen

Phase 1 Study of B-cell Depletion With Rituximab on Oral, Ocular and General Disease Manifestations in Patients With Primary Sjögren's Syndrome

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2200
        • Institute of Odontology, Faculty of Health Sciences, University of Copenhagen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To investigate the effect of Rituximab on subjective disease symptoms including oral dryness, ocular dryness, myoartralgia and fatigue.
Time Frame: Baseline, Day 22 after second treatment, 1 month, 3 months and 6 months after treatment.
Baseline, Day 22 after second treatment, 1 month, 3 months and 6 months after treatment.

Secondary Outcome Measures

Outcome Measure
Time Frame
To study the effect of Rituximab: on the structural changes (focal lymphocytic infiltrates) in the labial salivary gland tissue, including changes in the T- and B-cell ratio in the infiltrates as well as in the expression of M3-receptors
Time Frame: Baseline and 6 months after treatment
Baseline and 6 months after treatment
On the salivary gland function, incl. the production and composition of whole saliva and parotid saliva, the cellular signalling mechanisms and also the distribution of M3-receptors (M3R), the expression of aquaporins,
Time Frame: Baseline, 1 month, 3 months and 6 months after treatment
Baseline, 1 month, 3 months and 6 months after treatment
On the circulating serum autoantibodies (anti-SSA/-SSB, rheumatoid factors) and on antibodies against the M3R and α-fodrin and on the IgG level.
Time Frame: Baseline, 1 month, 3 months and 6 months after treatment
Baseline, 1 month, 3 months and 6 months after treatment
On the phenotype of circulating T- and B-cells as well as cytokines and immunoregulators, especially BLyS/BAFF.
Time Frame: Baseline, 1 month, 3 months and 6 months after treatment
Baseline, 1 month, 3 months and 6 months after treatment
On the function of the tear glandula, including the quantity and quality of tear as well as the extent of corneal changes.
Time Frame: Baseline, 1 month, 3 months and 6 months after treatment
Baseline, 1 month, 3 months and 6 months after treatment
To evaluate the side-effects in relation to the use of Rituximab-/placebo treatment.
Time Frame: After first and second treatment and after 1 month
After first and second treatment and after 1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Copenhagen

Collaborators

Rigshospitalet, Denmark

Investigators

  • Principal Investigator: Anne Marie Lynge Pedersen, PhD, DDS, Institute of Odontology, Faculty of Health Sciences, University of Copenhagen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2007

Primary Completion (Actual)

June 1, 2010

Study Completion (Actual)

August 1, 2010

Study Registration Dates

First Submitted

January 23, 2007

First Submitted That Met QC Criteria

January 23, 2007

First Posted (Estimate)

January 24, 2007

Study Record Updates

Last Update Posted (Actual)

March 14, 2017

Last Update Submitted That Met QC Criteria

March 11, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KF 02 282294
  • EudractCT-no. 2005-004740-31

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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