A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome

Persistently antiphospholipid antibody (aPL)-positive patients, age 18 - 75 years of age,
with anticoagulation-resistant manifestations of APS and fulfilling protocol defined study
inclusion criteria will receive two doses of Rituximab, and will be followed for 6 and 12
months for clinical and safety outcomes, respectively.

Patients are eligible to take part in this study if their blood test is persistently positive
for aPL and they have one or more of the aPL-related clinical problem(s) listed below: low
platelet (blood cells involved in the prevention of bleeding) count; anemia (deficiency of
red blood cells); heart valve disease; skin ulcers; kidney smal vessel blood clots; and/or
memory problems.

Inclusion Criteria:

- - Positive aPL profile defined as:

- Positive lupus anticoagulant test as defined by the International Society on
Thrombosis and Haemostasis, on two or more occasions, at least 12 weeks apart
and/or

- Positive anticardiolipin antibody (aCL) immunoglobulin G(Ig)G/M/A isotype,
present in > 40U, on two or more occasions, at least 12 weeks apart and/or

- Positive anti-β2-glycoprotein-I (aβ2GPI) IgG/M/A isotype, present in > 40U, on
two or more occasions, at least 12 weeks apart

AND

- Clinical features attributable to aPL that are resistant to warfarin and/or heparin:

- Persistent thrombocytopenia and/or

- Persistent autoimmune hemolytic anemia and/or

- Cardiac valve disease and/or

- Chronic skin ulcers and/or

- Renal thrombotic microangiopathy and/or

- Cognitive dysfunction with/without white matter changes

Exclusion Criteria (selected):

- > 4/11 American College of Rheumatology Classification Criteria for SLE

- Acute thrombosis

- History of stroke (only for patients with cognitive dysfunction)

- Positive Hepatitis B or C serology

- History of positive HIV

- Acute or chronic pancreatitis

- Treatment with any investigational agent within 4 weeks of screening

- Receipt of a live vaccine within 4 weeks prior to randomization

- Previous Treatment with Rituximab (MabThera® / Rituxan®)

- Previous treatment with Natalizumab (Tysabri®)

- Known active bacterial, viral fungal mycobacterial, or other infection

- Pregnancy

- Concomitant malignancies or previous malignancies, with the exception of adequately
treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the
cervix

- History of psychiatric disorder that would interfere with normal participation in this
protocol

- Significant cardiac or pulmonary disease