Clinical trial NCT00774852: Abatacept and Cyclophosphamide Combination Therapy for Lupus Nephritis
Official title: A Randomized, Double-Blind, Controlled, Phase II Multicenter Trial of CTLA4Ig (Abatacept) Plus Cyclophosphamide vs Cyclophosphamide Alone in the Treatment of Lupus Nephritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lupus Nephritis
Lupus Erythematosus, Systemic
Keywords: lupus
systemic lupus erythematosus
lupus nephritis
SLE
abatacept
CTLA4
CTLA4Ig
glomerulonephritis
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
First posted: 2008-10-17
Enrollment: 137
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Complete Response
timeFrame: Week 24
Secondary outcomes:
measure: Number of Participants With Partial Response
timeFrame: Week 24
measure: Number of Participants With a Complete or Partial Response
timeFrame: Week 52
measure: Number of Participants Who Achieved a Complete Response by Week 24 and Maintained the Complete Response Through Week 52
timeFrame: Week 52
measure: Number of Participants Fulfilling the Proteinuria and Prednisone Criteria of a Complete Response
timeFrame: Week 24
measure: Number of Participants Fulfilling the Proteinuria and Prednisone Criteria of a Partial Response
timeFrame: Week 24
measure: Number of Participants Who Achieved No Response at 24 Weeks and Continued in the Study
timeFrame: Week 104
measure: Number of Participants Who Achieved No Response at 24 Weeks and Continued in the Study , Achieving a Complete or Partial Response
timeFrame: Week 52
measure: Lupus Disease Activity - Participants Who Were Anti-dsDNA Positive at Baseline and Negative at Week 104
timeFrame: Week 104
measure: Lupus Disease Activity - Negative Anti-dsDNA
timeFrame: Week 104
measure: Lupus Disease Activity - Presence of Hypocomplementemia
timeFrame: Week 104
measure: Lupus Disease Activity - Frequency of Flares
timeFrame: Week 52
measure: Lupus Disease Activity - Patient Global Assessment
timeFrame: Week 104
measure: Lupus Disease Activity - Patient Global Assessment Percent Change From Baseline
timeFrame: Week 104
measure: Lupus Disease Activity - SF-36 Scores
timeFrame: Week 104
measure: Lupus Disease Activity - SF-36 Scores Percent Change From Baseline
timeFrame: Week 104
measure: Lupus Disease Activity - Total BILAG-2004
timeFrame: Week 52
measure: Proportion of Vaccinated Participants With a Competent Immune Response
timeFrame: Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Manhasset
country: United States
facility: Feinstein Institute
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: NY
country: United States
facility: Seligman Center for Advanced Therapeutics (NYU)
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Chapel Hill
country: United States
facility: UNC Chapel Hill
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Lupus Center of Excellence
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Guadalajara
country: Mexico
facility: Unidad de investigación en enfermedades crónico - degenerativas SC
state: Jalisco
city: Mexico City
country: Mexico
facility: El Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INNSZ)
Study officials:
affiliation: University of California, San Francisco
name: David Wofsy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Feinstein Institute
name: Betty Diamond, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: ACCESS Trial Group. Treatment of lupus nephritis with abatacept: the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study. Arthritis Rheumatol. 2014 Nov;66(11):3096-104. doi: 10.1002/art.38790.
citation: Wofsy D, Diamond B, Houssiau FA. Crossing the Atlantic: the Euro-Lupus Nephritis regimen in North America. Arthritis Rheumatol. 2015 May;67(5):1144-6. doi: 10.1002/art.39067. No abstract available.