Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis on Background of Cyclophosphamide or Rituximab Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 67
- 主要终点
- Proportion of Subjects Achieving Disease Response at Day 85
研究概览
简要总结
The aim of this trial is to optimize the treatment to induce remission for patients with non-life-threatening anti-neutrophil cytoplasmic antibody vasculitis (AAV). The intent is to reduce the toxicity of induction therapy by reducing the overall exposure to or eliminating entirely the use of systemic corticosteroids during the induction period with an inhibitor of the complement C5a receptor plus cyclophosphamide or rituximab.
详细描述
The primary safety objective of this study is to evaluate the safety and tolerability of CCX168 in subjects with AAV on background cyclophosphamide or rituximab treatment.
The primary efficacy objective is to evaluate the efficacy of CCX168 based on the Birmingham Vasculitis Activity Score (BVAS) version 3.
The secondary objectives of this study include assessment of the feasibility of reducing or eliminating the use of corticosteroids in the treatment of subjects with ANCA-associated vasculitis without the need for rescue corticosteroid measures and the effect of CCX168 on several disease parameters.
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
- Triple (Participant, Care Provider, Investigator)
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 postmenopausal or surgically sterile female subjects aged at least 18 years with new or relapsed AAV where treatment with cyclophosphamide or rituximab would be 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
- •Estimated glomerular filtration rate (eGFR) ≥ 20mL/min
- •Have at least one "major" item, or at least 3 non-major items, or at least 2 renal items on the BVAS version 3
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 of 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 high-dose intravenous corticosteroids within 4 weeks of screening
- •On an oral dose of a corticosteroid of more than 10mg prednisone-equivalent at the time of screening
- •Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred; received anti-TNF treatment, abatacept, alemtuzumab, IVIg or plasma exchange within 12 weeks of screening
研究组 & 干预措施
Placebo
Placebo plus a full dose of oral glucocorticoids for steps 1 and 2 of the study
干预措施: Placebo (Drug)
CCX168
30 mg Active study medication, plus either two-thirds reduced dose of oral glucocorticoids for step 1 of the study, or no oral glucocorticoids for step 2 of the study
干预措施: CCX168 (Drug)
结局指标
主要结局
Proportion of Subjects Achieving Disease Response at Day 85
时间窗: Baseline to Day 85
Disease response is defined as BVAS percentage reduction from baseline of at least 50% plus no worsening in any body system component.
次要结局
- Proportion of Patients Achieving Renal Response at Day 85(Baseline to Day 85)
- Proportion of Subjects Achieving Disease Remission at Day 85(Day 85)
- Percent Change From Baseline to Day 85 in BVAS(Baseline to Day 85)
- Change From Baseline to Day 85 in eGFR(Baseline to Day 85)
- Percent Change From Baseline to Day 85 in eGFR(Baseline to Day 85)
- Proportion of Subjects Achieving Urinary RBC Count <=5/Hpf at Any Time During the 84-day Treatment Period(Baseline to Day 85)
- Percent Change From Baseline to Day 85 in UACR(Baseline to Day 85)
- Percent Change From Baseline to Day 85 in Urinary MCP-1:Creatinine Ratio(Baseline to Day 85)
- Proportion of Subjects Requiring Rescue IV or Oral Glucocorticoid Treatment(Baseline to Day 85)
- Change From Baseline to Day 85 in the Vasculitis Damage Index(Baseline to Day 85)
- Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the SF-36 v2(Baseline, Day 29 & Day 85)
- Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the EQ-5D-5L(Baseline, Day 29 and Day 85)
- Time to First Achieving Urinary RBC Count <=5/Hpf at Any Point During the 84-day Treatment Period(Baseline to Day 85)
- Proportion of Subjects Achieving Urinary RBC Count <30/Hpf at Any Time During the 84-day Treatment Period(Baseline to Day 85)
- Time to First Achieving Urinary RBC Count <=30/Hpf at Any Point During the 84-day Treatment Period(Baseline to Day 85)
- Percent Change From Baseline to Day 85 in Urinary RBC Count(Baseline to day 85)