A Randomized, Double-Blind, Controlled, Phase II Multicenter Trial of CTLA4Ig (Abatacept) Plus Cyclophosphamide vs Cyclophosphamide Alone in the Treatment of Lupus Nephritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 137
- 试验地点
- 23
- 主要终点
- Number of Participants With Complete Response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Treatment
Abatacept plus Euro-lupus regimen
干预措施: abatacept (Drug)
Treatment
Abatacept plus Euro-lupus regimen
干预措施: cyclophosphamide (Drug)
Treatment
Abatacept plus Euro-lupus regimen
干预措施: azathioprine (Drug)
Treatment
Abatacept plus Euro-lupus regimen
干预措施: prednisone (Drug)
Treatment
Abatacept plus Euro-lupus regimen
干预措施: azathioprine placebo (Drug)
Control
Abatacept placebo plus Euro-lupus regimen
干预措施: cyclophosphamide (Drug)
Control
Abatacept placebo plus Euro-lupus regimen
干预措施: azathioprine (Drug)
Control
Abatacept placebo plus Euro-lupus regimen
干预措施: prednisone (Drug)
Control
Abatacept placebo plus Euro-lupus regimen
干预措施: abatacept placebo (Drug)
结局指标
主要结局
Number of Participants With Complete Response
时间窗: Week 24
Complete response definition: a serum creatinine \<= 1.2 mg/dL or \<=125% of the higher value at either screening or baseline visit, protein-to-creatinine ratio \<0.5, and prednisone dose tapered to \<=10 mg/day or prednisone dosing allowances in protocol. Participants had to meet all of the referenced criteria to be considered a complete responder (CR). Participants who discontinued treatment and/or terminated from the study in the first 24 weeks were defined as CR failures for all subsequent visits. CRs are those who successfully responded to treatment and have minimal activity of their lupus nephritis.
次要结局
- Number of Participants With Partial Response(Week 24)
- Number of Participants With a Complete or Partial Response(Week 52)
- Number of Participants Who Achieved a Complete Response by Week 24 and Maintained the Complete Response Through Week 52(Week 52)
- Number of Participants Fulfilling the Proteinuria and Prednisone Criteria of a Complete Response(Week 24)
- Number of Participants Fulfilling the Proteinuria and Prednisone Criteria of a Partial Response(Week 24)
- Number of Participants Who Achieved No Response at 24 Weeks and Continued in the Study(Week 104)
- Number of Participants Who Achieved No Response at 24 Weeks and Continued in the Study , Achieving a Complete or Partial Response(Week 52)
- Lupus Disease Activity - Participants Who Were Anti-dsDNA Positive at Baseline and Negative at Week 104(Week 104)
- Lupus Disease Activity - Negative Anti-dsDNA(Week 104)
- Lupus Disease Activity - Presence of Hypocomplementemia(Week 104)
- Lupus Disease Activity - Frequency of Flares(Week 52)
- Lupus Disease Activity - Patient Global Assessment(Week 104)
- Lupus Disease Activity - Patient Global Assessment Percent Change From Baseline(Week 104)
- Lupus Disease Activity - SF-36 Scores(Week 104)
- Lupus Disease Activity - SF-36 Scores Percent Change From Baseline(Week 104)
- Lupus Disease Activity - Total BILAG-2004(Week 52)
- Proportion of Vaccinated Participants With a Competent Immune Response(Week 52)