Abatacept and Cyclophosphamide Combination Therapy for Lupus Nephritis

Lupus nephritis is an inflammation of the kidney that occurs in patients with systemic lupus
erythematosus (SLE). It is caused by the immune system attacking the kidney and is among the
most serious complications of SLE: left untreated it can cause long term damage to the
kidneys or, in some cases, result in kidney failure.

One of the more common treatments for lupus nephritis is the "Euro-lupus" therapy. In this
therapy, patients receive three different drugs - cyclophosphamide, azathioprine and
prednisone - over the course of several months. However, some patients do not respond to
this therapy and many only show some improvement.

In this ACCESS trial for lupus nephritis, an experimental medication known as abatacept will
be added to the Euro-lupus therapy to assess if it works better than Euro-lupus therapy
alone. Abatacept is a man-made protein that suppresses parts of the immune system that can
cause autoimmune disease. While abatacept is experimental for lupus, it has been approved by
the FDA to treat rheumatoid arthritis. Abatacept is also being studied for use in other
autoimmune diseases, like multiple sclerosis and type 1 diabetes.

Participants in the ACCESS trial for lupus nephritis will receive bi-weekly intravenous
infusions of cyclophosphamide for 3 months, then will take azathioprine tablets daily for at
least 3 months more. Abatacept or a placebo will be administered every 2 weeks initially,
then every 4 weeks for at least the first 6 months. Treatment of abatacept or placebo and
azathioprine may continue for the remainder of the year. All participants will take
prednisone tablets daily during the entire study.

Because the ACCESS trial is a randomized, controlled study, each participant has a 50-50
chance (like flipping a coin) of receiving abatacept. Others will receive an inactive,
placebo form of the drug. Note however, that all participants will receive the Euro-lupus
therapy. As a blinded (masked) study, neither participants nor study physicians will know to
which group a person has been assigned.

All participants will undergo regular physical examinations, medical history and various
blood and urine tests. Many of these tests will be repeated throughout the study.
Participants will be asked to attend 18 study visits in the first year, and one study visit
at the end of the second year.

The study will reimburse participants for certain expenses incurred as part of the study.

Inclusion Criteria:

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

- Active lupus nephritis (defined by: kidney biopsy documentation within the last 12
months using International Society of Nephrology/Renal Pathology Society (ISN/RPS)
classification- proliferative nephritis, active urinary sediment, urine
protein-to-creatinine ratio > 1, low complement C3)

- Positive antinuclear antibody (ANA) test result at time of study entry

Exclusion Criteria:

- End stage renal disease

- Use of cyclophosphamide in the past year

- Neutropenia, thrombocytopenia, moderately severe anemia

- Active infection, including HIV, hepatitis B or C

- History of cancer, except carcinoma in situ and treated basal and squamous cell
carcinomas

- Pregnant or breastfeeding