Clinical trial NCT00774852
Conditions: Lupus Nephritis Lupus Erythematosus, Systemic
Keywords: lupus systemic lupus erythematosus lupus nephritis SLE abatacept CTLA4 CTLA4Ig glomerulonephritis
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2008-11-01; Completion date: 2014-06-01
Enrollment: 137 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is for individuals with lupus who have developed complications in their kidneys, or lupus nephritis. The study will determine whether adding the experimental medication abatacept to standard cyclophosphamide therapy is more effective in improving lupus nephritis than standard cyclophosphamide therapy by itself.

Detailed description:
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.

Arms: arm 1: Abatacept plus Euro-lupus regimen arm 2: Abatacept placebo plus Euro-lupus regimen
Interventions: intervention 1: abatacept intervention 2: cyclophosphamide intervention 3: azathioprine intervention 4: prednisone intervention 5: abatacept placebo intervention 6: azathioprine placebo
Intervention descriptions: intervention 1: Intravenous infusion (500-1000 mg, dep on weight) at weeks 0, 2, and 4, then every 4 weeks until week 24; continue to week 48 only if partial response at 24 weeks intervention 2: 500 mg intravenous infusion every 2 weeks for 12 weeks intervention 3: 2 mg/kg/day orally from weeks 12-28; continue until week 52 if only partial response observed at week 24 intervention 4: 60 mg/day for 2 weeks, then taper to 10 mg/day by 12 weeks, then continue on stable dose intervention 5: Intravenous infusion at weeks 0, 2, and 4, then every 4 weeks until week 24; continue to week 48 only if partial response at 24 weeks intervention 6: Oral capsule, daily from weeks 28 to 52, only if complete response observed at week 24

Protocol documents: