Anti-CD20 Antibody Therapy for Sjogren's Syndrome

SS is the second most common autoimmune disease; it is caused by immune cells attacking and
destroying the glands that produce tears and saliva, and occurs more often in women than in
men. Currently, there are no established disease-modifying treatments for SS. Traditional
treatment strategies for SS primarily address dryness symptoms. Rituximab targets the CD20
antigen on the surface of B cells, and was approved in 1997 for the treatment of patients
with low-grade or follicular B-cell non-Hodgkin's lymphoma. In a small study, rituximab was
also shown to relieve the symptoms of rheumatoid arthritis. Because SS is associated with the
development of B cell-related cancers and rituximab has the potential to treat autoimmune
disease, rituximab may alleviate the symptoms of SS. This study will evaluate the safety of
rituximab in people with SS.

This study will last 1 year. At 4 and 2 weeks before the start of the study, patients will
undergo medical and medication history assessment, a physical exam, blood and urine
collection, rheumatologic evaluation, an eye exam, and salivary gland tests. The screening
visit 4 weeks before study start will also include an electrocardiogram (ECG), a chest x-ray,
and a tuberculosis exam. Patients will receive IV rituximab at study entry and at Week 2;
blood collection will occur prior to infusion and post-infusion for pharmacokinetics studies.
There will be 6 follow-up study visits that will occur at Weeks 4, 8, 14, 26, 30, and 52.
Blood and urine collection; a physical exam; rheumatologic evaluation; and eye, skin, and
salivary gland tests will occur at selected study visits.

Inclusion Criteria:

- Weighs at least 40 kg (88.2 lbs)

- Meets European criteria proposed by the American-European Consensus Group for primary
Sjogren's syndrome

- Has 1 or more of the following symptoms of Sjogren's syndrome: fatigue; joint pain;
peripheral neuropathy; interstitial lung disease; leukocytoclastic vasculitis; renal
tubular acidosis; interstitial nephritis; severe parotid swelling; or other
extraglandular manifestations causing organ system dysfunction

- Agrees to use acceptable methods of contraception during the study and for 12 months
after the end of treatment

Exclusion Criteria:

- Active infection

- Chronic or persistent infection which might be worsened by immunosuppressive treatment
(e.g., HIV, hepatitis B or C, tuberculosis [TB])

- Known coronary artery disease, significant cardiac arrhythmias, or severe congestive
heart failure (New York Heart Association class III or IV)

- Current use of anticoagulants

- Prior use of rituximab

- Cyclophosphamide treatment within 24 weeks prior to screening

- Certain medications that may cause dry mouth

- Cytotoxic therapy with azathioprine, cyclosporine, methotrexate, or mycophenolate
mofetil within 4 weeks prior to screening

- Etanercept within 4 weeks prior to screening

- Adalumimab within 8 weeks prior to screening

- Infliximab within 12 weeks prior to screening

- Prednisone at greater than 10 mg/day within 2 weeks prior to screening. Patients who
have their steroid doses tapered to 10 mg/day or less within 2 weeks of screening are
not excluded.

- Definitive diagnosis of another autoimmune rheumatologic disease (e.g., systemic lupus
erythematosus, scleroderma, rheumatoid arthritis)

- History of alcohol or substance abuse

- History of immunoglobulin E (IgE)-mediated or non-IgE-mediated hypersensitivity

- Known anaphylaxis to mouse-derived proteins

- History of head and neck radiation therapy

- History of sarcoidosis (inflammation of unknown cause occurring in the lymph nodes,
lungs, liver, eyes, skin, or other tissues)

- History of graft-versus-host disease

- History of cancer. Patients who have had resected basal or major squamous cell
carcinoma, cervical dysplasia, or in situ cervical cancer Grade I within the last 5
years prior to study entry are not excluded.

- History of positive PPD without documentation of treatment for TB infection or
chemoprophylaxis for TB exposure

- Live vaccines within the 3 months prior to study entry

- Severe pulmonary disease. Patients who do not have undue fatigue or dyspnea following
ordinary physical activity are not excluded.

- Psychiatric disorder precluding informed consent

- Inability or unwillingness to follow study requirements

- Any current condition or treatment that, in the opinion of the investigator, may
interfere with the study

- Pregnancy