Protocol Number: 06-D-0181

Title:

A Randomized, Placebo Controlled, Proof of Concept, Study of Raptiva, a Humanized Anti-CD-11a Monoclonal Antibody, in Patients with Sjogren's Syndrome

Number:

06-D-0181

Summary:

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.

Sponsoring Institute:

National Institute of Dental And Craniofacial Research (NIDCR)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Up to 25 patients may be enrolled in this study to obtain at least 20 patients to complete the study and to allow for an estimated up to 20% early attrition rate. Eligible patients will have primary SS diagnosed according to the American-European Consensus Group Sjogren's Syndrome Classification Criteria. Subjects will be chosen based on their potential capacity to reverse the inflammatory process and at least partially recover the exocrine function in the salivary and lacrimal glands, as indicated in the inclusion criteria by requiring a minimal level of salivary flow as a marker of functional gland tissue. Pre-screening, which would include ophthalmologic evaluation, standard laboratory tests, and minor salivary gland biopsy, will be performed under the natural history protocol, and eligible patients will be offered to sign the informed consent for this protocol.

Age at entry at least 18 years

Must give written informed consent prior to entry in the protocol.

Must fulfill at least 4 of the 6 following criteria for Primary SS as defined by the American-European Consensus Group Sjogren's Syndrome Classification Criteria, including either item IV or VI, or fulfill 3 of the 4 objective criteria (III, IV, V, VI) [53] :

Ocular symptoms (at least one):

Dry eyes greater than 3 months

Foreign body sensation in the eyes

Use of artificial tears greater than 3x/day

Oral symptoms (at least one):

Dry mouth greater than 3 months

Swollen salivary glands

Need liquids to swallow dry foods

Ocular signs (at least one):

Schirmer test (without anesthesia) less than or equal to 5 mm/5 min

Positive vital dye staining (van Bijsterveld greater than or equal to 4)

Histopathology: Minor salivary gland biopsy showing focal lymphocyte sialoadenitis (focus score greater than or equal to 1 per 4 mm(2))

Oral signs (at least one):

Unstimulated whole salivary flow (less than or equal to 1.5 ml in 15 min)

Abnormal parotid sialography

Abnormal salivary scintigraphy

Autoantibodies (at least one):

Anti-SSA or Anti-SSB

One or more of the following:

Serum ANA level greater than or equal to 1EU

Serum Anti-SSA level greater than or equal to 20EU

Serum Anti-SSB level greater than or equal to 20EU

Serum RF level greater than or equal to 20 IU/ml

One or more of the following:

ESR greater than 25 mm/hr for men; ESR greater than 42 mm/hr for women

Serum IgG level greater than or equal to 1750 mg/dl

Serum CRP level greater than or equal to 0.08 mg/dl

Stimulated salivary flow of at least 0.1 ml/min.

Minor salivary gland biopsy with a focus score of greater than or equal to 4 within at most 12 months prior to the study enrollment.

Score of 3 or more on Oxford scale in at least one eye at the study entry.

Negative age- and gender- appropriate malignancy screening for breast, cervical, colorectal cancer for women; and prostate and colorectal cancer for men. Specifically:

-All women: pelvic exam with Papanicolaou smear within one year of study entry.

-Women age 40 and older: mammogram within 1 year of study entry,

-Both genders age 50 and older; stool screening for occult blood within one year, or flexible sigmoidoscopy or colonoscopy within five years

-Men age 50 and older: rectal examination or prostate specific antigen testing

EXCLUSION CRITERIA:

Past head and neck irradiation.

Hepatitis B, C, HIV, or HTLV infection.

History of lymphoma or monoclonal gammopathy of unknown significance (MGUS).

Sarcoidosis.

Graft-versus-host disease.

Women of childbearing potential are required to have a negative pregnancy test at screening.

Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control during and for a period of three months after the completion of the study.

Any therapy with human or murine antibodies or any experimental therapy within 3 months.

Therapy with cyclophosphamide, pulse methylprednisolone or IVIg, azathioprine, mycophenolate mofetil, oral cyclosporine or methotrexate within 4 weeks of first study treatment.

History of rituximab therapy.

Prednisone dose greater than or equal to 10 mg/day.

Allergy to murine or human antibodies.

History of anaphylaxis.

Serum creatinine greater than 2.0 mg/dl.

History of any malignancy.

Active infection that requires the use of intravenous antibiotics and does not resolve within 1 week of Day 1.

Any active viral infection that does not resolve within 10 days prior to Day 1.

WBC less than 2000/microL or ANC less than 1500/microL or Hgb less than 9.0 g/dL or platelets less than 150,000/microL or absolute lymphocyte count less than or equal to 500/microL.

ALT and/or AST greater than 1.5x upper limit of normal (ULN) or alkaline phosphatase greater than 1.5x ULN.

Significant concurrent medical condition that, in the opinion of the Principal Investigator, could affect the patient's ability to tolerate or complete the study.

Live vaccines within 12 weeks of first treatment.

Special Instructions:

Currently Not Provided

Keywords:

Adhesion Molecule

Interventional Study

Immunomodulation

MRI

Autoimmunity

Recruitment Keyword(s):

Sjogren Syndrome

SS

Condition(s):

Sjogren's Syndrome

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Raptiva

Supporting Site:

National Institute of Dental and Craniofacial Research

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Skopouli FN, Moutsopoulos HM. Autoimmune epitheliitis: Sjogren's syndrome. Clin Exp Rheumatol. 1994 Nov-Dec;12 Suppl 11:S9-11. Review.

Atkinson JC, Fox PC. Sjogren's syndrome: oral and dental considerations. J Am Dent Assoc. 1993 Mar;124(3):74-6, 78-82, 84-6. Review.

Garcia-Carrasco M, Ramos-Casals M, Rosas J, Pallares L, Calvo-Alen J, Cervera R, Font J, Ingelmo M. Primary Sjogren syndrome: clinical and immunologic disease patterns in a cohort of 400 patients. Medicine (Baltimore). 2002 Jul;81(4):270-80. Review. No abstract available.

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