Abatacept and Cyclophosphamide Combination Therapy for Lupus Nephritis (ACCESS)

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 2

Conditions: Lupus Erythematosus, Systemic; Lupus Nephritis

Treatments: Drug: prednisone; Drug: abatacept placebo; Drug: azathioprine placebo; Drug: azathioprine; Drug: cyclophosphamide; Drug: abatacept

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00774852

DAIT ITN034AI

Details and patient eligibility

About

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.

Full 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.

Enrollment: 137 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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137 participants in 2 patient groups, including a placebo group

Treatment

Experimental group

Description:

Abatacept plus Euro-lupus regimen

Treatment:

Drug: azathioprine placebo

Drug: abatacept

Drug: cyclophosphamide

Drug: azathioprine

Drug: prednisone

Control

Placebo Comparator group

Description:

Abatacept placebo plus Euro-lupus regimen

Treatment:

Drug: cyclophosphamide

Drug: azathioprine

Drug: abatacept placebo

Drug: prednisone