Rituximab Treatment in Sjogren's Syndrome

University Medical Center Groningen (UMCG)

Status and phase

Completed

Phase 2

Phase 1

Conditions

Sjogren's Syndrome

Treatments

Drug: rituximab (anti-CD20)

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00363350

METc2005.229

Details and patient eligibility

About

This study is an evaluation of the effect of rituximab compared to placebo in combination with steroids on salivary flow and serological and clinical parameters in patients with primary SS.

Full description

Study design:

phase II trial

Study objective:

evaluation of the effect of rituximab compared to placebo in combination with steroids on salivary flow and serological and clinical parameters in patients with primary SS

Number of participating centres:

Duration:

follow-up 48 weeks

Study medication:

2 infusions on day 1 and day 15 rituximab infusions (1000 mg) or placebo infusions intravenous infusion of 100 mg of methylprednisolone before infusion of rituximab (or the placebo for rituximab), together with 60 mg per day of oral prednisone on days 2, 3, 16 and 17, 30 mg per day on days 4, 5, 18 and 19 and 15 mg per day on days 6 and 20

Primary objective/endpoint:

stimulated salivary gland function (stimulated submandibular/sublingual and parotid saliva)

Secondary objectives/endpoint:

Functional parameters Laboratory parameters Subjective parameters Histological/Molecular parameters

Number of subjects:

30 patients with primary SS (20 patients rituximab treatment, 10 patients placebo)

Enrollment

30 estimated patients

Sex

All

Ages

18 to 85 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Stimulated whole saliva secretion ≥ 0,15 ml/min
Male or female > 18 years
Primary SS according to the revised European - U.S. criteria(22)
Positive autoantibodies (IgM-Rf > 10 and SS-A and/or SS-B)
Parotid gland biopsy (paraffine material and fresh frozen tissue) with characteristic features of SS performed at time of inclusion (no longer than 12 months ago)
Use of reliable method of contraception during the study
Written informed consent

Exclusion criteria

The presence of any other connective tissue disease
Preceding treatment with anti-TNF or other monoclonal antibodies
Use of prednisone, hydroxychloroquine less than 1 month ago
Use of MTX, cyclophosphamide, cyclosporin, azathioprine and other DMARDS less than 0,5 year ago
Serum creatine > 2.8 mg/dl (250 micromol/l)
ASAT or ALAT outside 1.5 x upper normal range of the laboratory
Hb < 9 g/dl (5.6 mmol/l) for males and 8.5 g/dl (5.3 mmol/l) for females
Neutrophil granulocytes less than 0.5 x 109/l
Platelet count less then 50 x 109/l
Positive pregnancy test or breast-feeding
History of alcohol or drug abuse
Serious infections
Underlying cardiac, pulmonary, metabolic, renal or gastrointestinal conditions, chronic or latent infectious diseases or immune deficiency which places the patient at an unacceptable risk for participation in the study
History of any malignancy with the exception of completely resected basal cell carcinoma of the skin