Treating Systemic Lupus Erythematosus (SLE) Patients With CTLA4-IgG4m (RG2077)

SLE is a chronic, inflammatory autoimmune disorder that may affect many organ systems,
including the skin, joints, and internal organs. RG2077 has been studied for use in multiple
sclerosis, another autoimmune disorder. This study will evaluate the safety and efficacy of
RG2077 in SLE patients who are currently receiving cyclophosphamide.

This trial is composed of two parts. The first part is a dose-escalation study in which
participants will receive one of two doses of RG2077 (0.2 mg/kg or 2 mg/kg); this part of
the study will last 60 days. At screening, patients will have an IV catheter inserted into
their arms for administration of cyclophosphamide and RG2077. Patients will also have
medical and medication history assessments, a comprehensive physical exam, and blood and
urine tests. There are 5 study visits for the first part of the trial; these will occur at
screening, at study entry, and Days 1, 14, and 28. Selected visits will include physical
exam, vital signs measurement, blood and urine tests, and disease activity assessment. At
Days 7 and 60, patients will be contacted by phone to report their medication history and
any adverse effects they have experienced.

The second part of the study will evaluate a single 10 mg/kg dose of RG2077; this part of
the study will last 90 days. In the study, participants will be randomly assigned to one of
two groups. At the start of the study, Group 1 participants will receive RG2077 and
cyclophosphamide and Group 2 participants will receive cyclophosphamide only. There will be
9 study visits; these will occur at study screening, study entry, and Days 1, 4, 7, 14, 28,
and 60. At selected visits, patients will undergo physical exam, vital signs measurement,
blood tests and urine tests, and disease activity assessment.

Inclusion Criteria:

- Diagnosis of SLE by American College of Rheumatology (ACR) criteria

- Concurrent treatment with intravenous cyclophosphamide (500 to 1000 mg/m2) for at
least one of the following manifestations of lupus: World Health Organization (WHO)
class III, IV, or V lupus nephritis; British Isles Lupus Assessment Group (BILAG)
score of A for vasculitis; BILAG score of A for cytopenia; BILAG score of A for
nervous system

- Stable medication regimen for at least 4 weeks prior to study entry

- Weight between 40 kg (88.2 lbs) and 125 kg (275.6 lb)

- Willing to use acceptable forms of contraception

Exclusion Criteria:

- Moderately severe anemia (hemoglobin less than 8 mg/dL)

- Neutropenia (absolute neutrophil count less than 1,500/mm3)

- Thrombocytopenia (platelets less than 50,000/mm3)

- Positive tuberculin (PPD) test without evidence of prior treatment or administration
of bacille Calmette-Guérin (BCG) vaccine

- Active infections, including HIV and hepatitis B or C

- Receipt of a live vaccine within 3 months of study entry

- End-stage renal disease with creatinine clearance less than 20 ml/min/1.73 m2

- History of cancer. Patients with a history of carcinoma in situ and treated basal and
squamous cell carcinomas are not excluded.

- Pregnant or breastfeeding