Targeting Complement Activation in Antineutrophil Cytoplasmic Autoantibodies (ANCA)-Vasculitis
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Birmingham Vasculitis Activity Score (BVAS)
研究概览
简要总结
The purpose of this research study is to see if Eculizumab (Soliris®) can safely be used in addition to conventional therapy in patients with active ANCA (Antineutrophil Cytoplasmic Autoantibodies ) vasculitis and lead to a more rapid decrease in disease activity.
ANCA vasculitis is an inflammation of the small vessels whereby ANCA antibodies inappropriately activate one's own white blood cells (neutrophils) and cause damage to the small blood vessels.
详细描述
Recent laboratory studies have identified that an important pathway of inflammation called the "complement pathway" may play an important role in how Antineutrophil Cytoplasmic Autoantibodies (ANCA) cause damage to the blood vessels. Eculizumab is a monoclonal antibody that targets a key component of the complement pathway named C5, and blocks its activation.
In a mouse model of ANCA vasculitis, it has been shown that blocking C5 activation can block the development of vasculitis or greatly reduce its severity.
The researchers in this study would like to see if taking eculizumab, in addition to the drugs usually used to treat ANCA vasculitis, would be beneficial in treating ANCA vasculitis.
Currently, the conventional treatment of ANCA vasculitis consists of corticosteroids and cyclophosphamide. The corticosteroids are given as by vein (methylprednisolone) for 3 days followed by prednisone by mouth daily for about 4-5 months. Cyclophosphamide is typically given by vein every 4 weeks for at least 3 months, but sometimes longer depending on whether the vasculitis is still active or not. After the vasculitis is in remission, a maintenance treatment with azathioprine or mycophenolate mofetil may be used. For patients who cannot tolerate cyclophosphamide, or who have received it in large doses previously, another medication called rituximab may be used instead. However, patients who need rituximab or have recently been treated with rituximab cannot participate in this study.
The study drug, eculizumab, is Food and Drug Administration (FDA) approved for indications other than ANCA vasculitis. It is an investigational drug and it is NOT FDA-approved for the treatment of ANCA vasculitis.
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
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with active Antineutrophil Cytoplasmic Autoantibodies (ANCA) glomerulonephritis and/or small vessel vasculitis with de novo or relapsing disease (BVAS≥5).
- •Patients must have a current or a history of positive ANCA by the ELISA technique.
- •De novo or relapsing disease requiring immunosuppression.
- •Patients must have evidence of active glomerulonephritis as evidenced by the presence of glomerular hematuria (dysmorphic Red Blood Cells (RBCs) or RBC casts) with or without an increase in serum creatinine.
- •Patients will be eligible within 10 days of commencing induction therapy (i.e., they may have already received pulse methylprednisolone and first dose of cyclophosphamide).
排除标准
- •Pregnancy or lactation, or women of child bearing potential who are not willing or able to comply with 2 contraceptive methods.
- •Patients with severe renal failure: creatinine > 6 mg/dL or receiving hemodialysis and/or receiving plasmapheresis therapy.
- •Patients with severe pulmonary hemorrhage requiring ventilation and/or plasmapheresis therapy.
- •Patients with active bacterial or viral infection.
- •Absolute neutrophils count < 1000/mm^3 to minimize the risk of infections
- •Hemoglobin < 8.5 g/dL
- •Prior therapy with a monoclonal antibody (for example rituximab)within the previous 6 months. Peripheral CD-20 B-cells count <= 1% due to rituximab even longer than 6 months.
- •Severe coexisting conditions precluding immunosuppressive therapy or conditions requiring intravenous antibiotic therapy.
- •History of infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV), HIV, tuberculosis or syphilis.
研究组 & 干预措施
Standard of care
Standard of care for ANCA vasculitis treatment- depends on severity of disease and individual characteristics and medical history of each patient so this won't be described here.
干预措施: Standard of care treatment (Drug)
Eculizumab arm
Standard of care for ANCA vasculitis + eculizumab treatment
Standard of care for ANCA vasculitis treatment- depends on severity of disease and individual characteristics and medical history of each patient so this won't be described here.
干预措施: eculizumab (Drug)
结局指标
主要结局
Birmingham Vasculitis Activity Score (BVAS)
时间窗: 12 weeks
Change in disease activity as measured by BVAS at 12 weeks.
次要结局
- Complement levels elevation(up to 52 weeks)
- Birmingham Vasculitis Activity Score(BVAS)(up to 52 weeks)
- Change in complement levels(from baseline to week 12)
- Normalisation of complement activation(up to 52 weeks)
- change in complement levels 2(up to 52 weeks)
- Birmingham Vasculitis Activity Score (BVAS) 2(up to 52 weeks)