Alemtuzumab for ANCA Associated Refractory Vasculitis - a Study of Safety and Efficacy
试验速览
- 阶段
- 4 期
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Proportion of patients with a vasculitis response at 6 months
研究概览
简要总结
Overview:
This open label, randomized, multi-centre study will enroll and treat 24 patients with refractory AAV.
Aims:
To determine the clinical response and severe adverse event rates associated with alemtuzumab therapy among patients with relapsing or refractory ANCA associated vasculitis (AAV).
Hypothesis:
Treatment with alemtuzumab induces sustained remission in AAV and will reduce immunosuppressive and steroid exposure.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of AAV, according to a standardized definition
- •Active vasculitis with at least one severe or three non severe items of BVAS/WG activity (equivalent to BVAS/WG>3)
- •Previous therapy with either cyclophosphamide or methotrexate, in combination with prednisolone for at least 3 months.
排除标准
- •Age less than 18 or greater than 60 years
- •Creatinine > 150μmol/l (1.7mg/dl)
- •Total white count < 4x109/l or lymphocyte count < 0.5x109/l, or IgG < 5g/L, or neutrophil count < 1.5x109/l.
- •Severe lung haemorrhage with hypoxia (<85% on room air)
- •Severe gastrointestinal, central nervous system or cardiac vasculitis
- •Previous therapy with:
- •Alemtuzumab at any time
- •IVIg, infliximab, etanercept, adalimumab, abatacept, anti-thymocyte globulin or plasma exchange in past three months
- •Rituximab within the past 6 months
- •Intensive care unit requirement
- •Active infection with HIV, hepatitis B or hepatitis C or other infection requiring parenteral or long-term oral antibiotics
- •History of ITP or platelet count at screening below 50,000 x 106/l
- •Pregnancy or inadequate contraception in pre-menopausal women
- •Breast feeding
- •Any condition judged by the investigator that would cause the study to be detrimental to the patient.
- •Any other multisystem autoimmune disease including Churg Strauss angiitis, systemic lupus erythematosus, anti-GBM disease and cryoglobulinaemia
- •Any previous or current history of malignancy (other than resected basal cell carcinoma)
研究组 & 干预措施
Alemtuzumab - high dose (60mg)
Alemtuzumab 30mg will be administered on Day 1 and Day 2 at 0 and 6 months
干预措施: Alemtuzumab (Drug)
Alemtuzumab - low dose (30mg)
Alemtuzumab 15mg will be administered on Day 1 and Day 2 at 0 and 6 months
干预措施: Alemtuzumab (Drug)
结局指标
主要结局
Proportion of patients with a vasculitis response at 6 months
时间窗: 6 months
Response includes patients in complete and partial remission. Complete remission (CR) is defined as a BVAS/WG of 0 for at least one month. Partial response (PR) is the absence of severe BVAS/WG items and at least 50% fall in BVAS/WG score from baseline.
Proportion of patients with a severe adverse event
时间窗: 6 months
次要结局
- Proportion of patients with treatment failure(12 months)
- Combined damage assessment (CDA) scores(12 months)
- Non severe adverse events(12 months)
- Cumulative dose of corticosteroids(12 months)
- Time to remission(6 months)
- Relapse(12 months)
- Change in SF-36(12 months)