Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 7
- 主要终点
- Remission of Vasculitis
研究概览
简要总结
Wegener's granulomatosis is a primary systemic vasculitis characterized by granulomatous and necrotizing inflammation predominantly affecting the respiratory tract and the kidneys. Conventional therapy of Wegener's granulomatosis with cyclophosphamide and corticosteroids is limited by incomplete remissions and a high relapse rate. Patients accumulate irreversible damage due to the disease and the consequences of prolonged drug exposure. The efficacy and safety of an alternative immunosuppressive drug, gusperimus, was evaluated in patients with refractory disease. A prospective, international, nulti-centre, single limb, open label study. Entry required active Wegener's granulomatosis with a Birmingham Vasculitis Activity Score (BVAS) >=4 and previous therapy with cyclophosphamide or methotrexate. Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status. Gusperimus, 0.5mg/kg/day, was self-administered by subcutaneous injection in six treatment cycles of 21 days with a seven day washout between cycles. Cycles were stopped early for white blood count < 4,000/mm3. The primary endpoint was complete remission (BVAS=0 for at least 2 months) or partial remission (BVAS<50% of entry score). After the sixth cycle azathioprine was commenced and follow-up continued for a further six months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of WG according to American College of Rheumatology (ACR) and Chapel Hill Consensus Conference (CHCC) definition
- •BVAS >= 4
- •Total disease duration >= 3 months treated with CYC or >= 6 months with MTX
- •Age 18 - 80
- •WBC >= 4,000/mm3, haemoglobin >= 8g/dl, neutrophils >= 2,500/mm3, platelets >= 100,000/mm3
- •ALT, bilirubin and alkaline phosphatase levels within 2x the upper limits of normal
- •Documented to be non-pregnant by serum/urine pregnancy test
- •Willing to participate in this study
- •Provide signed informed consent
- •Able and prepared to self-administer the study drug or have a close friend/relative able to do this
排除标准
- •Participation in another clinical research study
- •Pregnant or nursing mothers and women of childbearing age not using appropriate contraception
- •Clear evidence of active disease due to bacteria/viral infection
- •Patient has an unacceptable risk for participation in a study of immunosuppressive therapy
- •History of substance abuse or psychotic disorders
- •Previous treatment with Gusperimus
研究组 & 干预措施
1
Gusperimus
干预措施: Gusperimus (Drug)
结局指标
主要结局
Remission of Vasculitis
时间窗: At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks
The primary efficacy outcome measure was remission of vasculitis. Complete remission was defined as a Birmingham vasculitis activity score (BVAS) of 0 sustained for at least 2 months. Partial remission was defined as a reduction in BVAS of 50% or more, sustained for at least 2 months, when compared with the BVAS at entry. Entry required active Wegener's granulomatosis with a BVAS \>= 4. Their disease had to be active, as measured with BVAS in which clinical manifestations caused by active vasculitis are scored on a list of predefined organ-specific items.
次要结局
- Haematuria(At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks)
- Duration of Clinical Response(At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks, End of treatment period, and 3 and 6 months of follow-up period)
- ANCA(At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks)
- CRP(At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks)
- Vasculitis Damage Index (VDI)(At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks, 6 months of follow-up period)
- Creatinine(At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks)
- SF-36(At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks)