Pilot Study of Raptiva to Treat Sjogren's Syndrome
Condition: Sjogren's Syndrome
MeSH terms: Sjogren's Syndrome; Syndrome
Intervention: Raptiva
Intervention description: During the first phase of the study, subjects are randomized in a double blind fashion to receive weekly subcutaneous injections of efalizumab (Raptiva) or placebo (weeks 0-12). The second 12 weeks long phase is open label with all subjects receiving weekly subcutaneous injections of efalizumab.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Adhesion Molecule; Interventional Study; Immunomodulation; Autoimmunity; Sjogren Syndrome; SS

Summary:

      This study will examine the effect of the drug Raptiva (efalizumab) in patients with
      Sjögren's syndrome (SS), an autoimmune disease affecting the glands producing saliva & tears.
      The cause of SS is not known, but inflammation plays an important role. Raptiva is approved
      by the Food and Drug Administration to treat psoriasis, an inflammatory skin disease.
      Patients 18 years of age & older with SS may be eligible for this study. Candidates are
      screened with a history & physical examination, chest x-ray, and oral & 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 & placebo are injected under the skin
      once a week. Evaluation during treatment & for 2 months after treatment as follows:

      Full comprehensive evaluations (beginning of the study, at weeks 13 & 25 and 2 months after
      treatment ends):

        -  Physical examination & blood draw.

        -  Saliva collection done 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 & sides of the tongue at 30-second intervals
           to stimulate saliva production.

        -  Eye exam for tear gland function.

        -  Questionnaires about mouth & eye dryness, energy level and overall well-being.

        -  Lip biopsy (screening & week 13 visits only). A few minor salivary glands are removed
           for examination under a microscope. The lower lip is numbed, a small cut is made on the
           inside of the lip, and several glands are removed. The cut is closed with a few stitches
           that are removed after 5 to 7 days.

        -  Magnetic resonance imaging 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 metal
           cylinder containing a strong magnetic field). The head is held in place during the scan.
           The study lasts about 90 minutes.

        -  Short evaluations at weeks 3, 5, 9, 15, 17, 21 and 1 month after treatment ends.

        -  Medical history & 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
    

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 0.8 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.