A Randomized, Double-Blind, Placebo-Controlled, Dose Assessment Phase 2 Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 42
- 主要终点
- Incidence of Adverse Events
研究概览
简要总结
The aim of this trial is to test the safety and efficacy of two dose regimens of the complement C5a receptor CCX168 in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
Funding Source - FDA OOPD
详细描述
Complement 5a and its receptor C5aR (CD88) is involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This is a randomized, double-blind, placebo-controlled Phase 2 study to evaluate the safety and efficacy of the C5aR inhibitor CCX168 in subjects with ANCA-associated vasculitis. The aim of this trial is to test the safety and efficacy of two dose regimens of the complement C5a receptor CCX168 in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis or renal limited vasculitis
- •Male and female subjects, aged at least 18 years, with new or relapsed AAV where treatment with cyclophosphamide or rituximab would be required
- •Use of adequate contraception during, and for at least the three months after, any administration of study medication is required
- •Positive indirect immunofluorescence (IIF) test for P-ANCA or C-ANCA, or positive ELISA test for anti-proteinase-3 (PR3) or anti-myeloperoxidase (MPO) at screening
- •Have at least one "major" item, or at least 3 other items, or at least 2 renal items on the Birmingham Vasculitis Activity Score (BVAS) version 3
- •Estimated glomerular filtration rate (eGFR) ≥ 20 mL per minute
排除标准
- •Severe disease as determined by rapidly progressive glomerulonephritis, alveolar hemorrhage, hemoptysis, rapid-onset mononeuritis multiplex or central nervous system involvement
- •Any other multi-system autoimmune disease
- •Medical history of coagulopathy or bleeding disorder
- •Received cyclophosphamide within 12 weeks prior to screening; if on azathioprine, mycophenolate mofetil, or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1
- •Received intravenous corticosteroids, >3000 mg methylprednisolone equivalent, within 12 weeks prior to screening
- •Received an oral daily dose of a corticosteroid of more than 10 mg prednisone-equivalent for more than 6 weeks continuously prior to the screening visit
- •Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred; received anti-tumor necrosis factor (TNF) treatment, abatacept, alemtuzumab, intravenous immunoglobulin (IVIg), belimumab, tocilizumab, or plasma exchange within 12 weeks prior to screening
研究组 & 干预措施
Placebo, twice daily + standard of care
Capsule, placebo, twice daily + standard of care for 12 weeks
干预措施: Placebo, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids (Other)
CCX168 low dose plus standard of care
Capsule, 10 mg, twice daily + standard of care for 12 weeks
干预措施: CCX168 10 mg, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids (Drug)
CCX168 high dose plus standard of care
Capsule, 30 mg, twice daily + standard of care for 12 weeks
干预措施: CCX168 30 mg, twice daily, cyclophosphamide/rituximab plus glucocorticoids (Drug)
结局指标
主要结局
Incidence of Adverse Events
时间窗: Baseline to Day 85
This is a safety study to assess the overall rates of treatment-emergent adverse events (TEAEs) across all study arms.
Proportion of Patients Achieving Disease Response Based on BVAS at Day 85
时间窗: Day 85
Proportion of Patients achieving 50% reduction in the Birmingham Vasculitis Activity Score \[BVAS\] at Day 85 and no worsening in any body system component at day 85
次要结局
- Proportion of Subjects Achieving Disease Remission Based on BVAS at Day 85.(Day 85)
- Proportion of Subjects Achieving Early Disease Remission Based on BVAS of 0 at Days 29 and 85.(Day 29 and 85)
- Percent Change From Baseline to Day 85 in BVAS.(Baseline to Day 85)
- Proportion of Subjects With Hematuria and Albuminuria at Baseline Who Showed a Renal Response at Day 85(Day 85)
- Change in Estimated Glomerular Filtration Rate at Day 85(Baseline to Day 85)
- Percentage Change in Estimated Glomerular Filtration Rate at Day 85(Baseline to Day 85)
- Percent Change of Urinary Red Blood Cells in Patient With Hematuria From Baseline to Day 85(Baseline to Day 85)
- Change From Baseline to Day 85 in the VDI(Baseline to Day 85)
- Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2(Baseline to Day 85)
- Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L(Baseline to Day 85)
- Percent Change of Urinary Albumin:Creatinine Ratio in Patients With Albuminuria From Baseline to Day 85(Baseline to Day 85)
- Percent Change of Urinary MCP-1:Creatinine Ratio From Baseline to Day 85(Baseline to Day 85)
- Proportion of Subjects Requiring Rescue Glucocorticoid Treatment From Baseline to Day 85(Baseline to Day 85)