Raptiva to Treat Sjogren's Syndrome
This study will examine the effect of the drug Raptiva (efalizumab) in patients with Sjogren's syndrome, an autoimmune disease that mainly affects the glands producing saliva and tears. The cause of Sjogren's syndrome is not known, but inflammation plays an important role in the disease. Raptiva is approved by the Food and Drug Administration to treat psoriasis, an inflammatory skin disease.
Patients 18 years of age of age and older with Sjogren's syndrome may be eligible for this study. Candidates are screened with a history and physical examination, chest x-ray, and oral and eye examinations.
Participants are randomly assigned to receive either Raptiva or placebo (an inactive substance that looks like Raptiva) for the first 3 months of the study. For the next 3 months, all participants receive Raptiva. Both Raptiva and placebo are injected under the skin once a week. During treatment and for 2 months after treatment, patients are evaluated as follows:
Full comprehensive evaluations (at the beginning of the study, at week 13, at week 25 and 2 months after treatment ends):
- Physical examination and blood draw.
- Saliva collection. Saliva samples are collected in two ways: 1) suctions cups connected to collection tubes are placed over the salivary gland ducts in the mouth and under the tongue; and 2) a sour-tasting liquid is applied to the top and sides of the tongue at 30-second intervals to stimulate saliva production.
- Eye exam to evaluate tear gland function.
- Questionnaires about mouth and eye dryness, energy level and overall well being.
- Lip biopsy (at screening and week 13 visits only). A few minor salivary glands under the skin of the lower lip are removed for examination under a microscope. The lower lip is numbed, a small cut is made, and several tiny glands are removed. The cut is then closed with a few tiny stitches that are removed after 5 to 7 days.
- Magnetic resonance imaging (MRI) of the parotid glands (salivary glands near the ear) at weeks 1, 13 and 25. The patient lies on a stretcher that is moved into the scanner (a narrow metal cylinder containing a strong magnetic field). The head is held in place during the scan with a plastic strap and foam pads. The study lasts about 90 minutes.
Short evaluations (at weeks 3, 5, 9, 15, 17, 21 and 1 month after treatment ends):
- Medical history and physical examination, blood draw, evaluation for changes in symptoms and side effects, review of current medications at weeks 3, 9, 15 and 21
- Laboratory tests, evaluation for changes in symptoms and side effects, review of current medications, saliva collection without the sour liquid and short evaluation of tear production at weeks 5 and 17
- Blood tests at week 29.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized, Placebo Controlled, Proof of Concept, Study of Raptiva, a Humanized Anti-CD-11a Monoclonal Antibody, in Patients With Sjogren's Syndrome|
- Improvement in exocrine function [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Response defined by a composite criteria [ Time Frame: 3 months ] [ Designated as safety issue: No ]
|Study Start Date:||June 2006|
|Study Completion Date:||January 2009|
|Primary Completion Date:||January 2009 (Final data collection date for primary outcome measure)|
The LFA-1/ICAM-1 interaction is important in migration of lymphocytes to inflammatory sites, T-lymphocyte activation, antigen presentation, and maintaining the integrity of the immunologic synapse. In both murine and human Sjogren's Syndrome, increased expression of LFA-1 was found on activated lymphocytes, and increased expression of ICAM-1 was present on the activated endothelial cells in the diseased salivary and lacrimal glands. In animal models, blockade of the LFA-1/ICAM-1 interaction resulted in reduction of glandular inflammation.
Raptiva (efalizumab) is a recombinant humanized monoclonal antibody that binds to human CD11a, the alpha-subunit of Leukocyte Function Antigen-1 (LFA-1) and inhibits the LFA-1/ICAM-1 interaction. Raptiva is an FDA-approved medication for treatment of mild-to-moderate psoriasis.
In this pilot, proof of concept, randomized, double-blind, placebo-controlled study, up to 25 patients with Sjogren's syndrome may be enrolled. In the first, double-blind phase of the study, patients will be randomized and treated with weekly subcutaneous (SC) injections of either Raptiva (1mg/kg) or placebo for 12 weeks. In the second open label phase, all patients will be treated with weekly SC injections of Raptiva (1mg/kg) for another 12 weeks and then followed for an additional 8 weeks. Safety will be evaluated using standard clinical and laboratory parameters. To assess the potential effect of Raptiva on Sjogren's syndrome, minor salivary gland biopsy, oral and ocular evaluations, and measurements of surrogate markers of inflammation will be compared between the Raptiva and placebo treated groups before and after the treatment. Patients who either do not tolerate the drug or have worsening in their disease activity will be withdrawn from the protocol.
If Raptiva is well tolerated in this study and the treatment is associated with improvement in clinical parameters of Sjogren's Syndrome, further large studies of efficacy are planned.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|