A Multicenter, Randomized, Open-lable, Parallel-controlled, Phase I/II Trial to Study Efficacy and Safety of Substitution of Glucocorticoid for BDB-001 Injection in Patients With ANCA-associated Vasculitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 93
- 试验地点
- 22
- 主要终点
- The proportion of patients achieving disease complete remission or partial remission assessed by Birmingham Vasculitis Activity Score (BVAS)
研究概览
简要总结
The aim of the trial is to study the efficacy and safety of treatment with BDB-001 Injection substitution of glucocorticoid in patients with ANCA-associated 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
- •18 years old≤Age≤75 years old, male or female;
- •Diagnosis of granulomatosis with polyangiitis(GPA) or microscopic polyangiitis(MPA)；
- •Newly diagnosed or relapsed GPA or MPA that requires treatment with cyclophosphamide(CYC) and glucocorticoids(GCs)；
- •Positive test for anti-proteinase 3(PR3) or anti-myeloperoxidase (MPO)；
- •Estimated glomerular filtration rate ≥15 mL/minute/1.73 m^2；
- •At least 1 major item, or at least 3 non-major items, or at least the 2 renal items on BVAS；
排除标准
- •Active tuberculosis infection;
- •Severe disease as determined by rapidly progressive glomerulonephritis, alveolar hemorrhage requiring pulmonary ventilation support, rapid-onset mononeuritis multiplex or central nervous system involvement；
- •Any other known multi-system autoimmune disease including eosinophilic granulomatosis with polyangiitis (Churg-Strauss), systemic lupus erythematosus, IgA vasculitis (Henoch-Schönlein), rheumatoid vasculitis,anti-glomerular basement membrane disease, or cryoglobulinemic vasculitis；
- •HBsAg positive,or HBcAb positive and HBV-DNA positive；
- •Received CYC within 3 months before the first administration or Received rituximab(RTX) within 12 months before the first administration；
- •Received glucocorticoid shock therapy within 4 weeks before the first administration；
- •Received an oral daily dose of a GC of > 10 mg prednisone-equivalent for more than 6 weeks continuously before the first administration；
- •Received a anti-tumor necrosis factor and other biological agents treatment within 12 weeks before the first administration；
- •Received Continuous dialysis treatment for 12 weeks or more before the first administration; Received Dialysis within 1 week before the first administration;
- •Received intravenous immunoglobulin (Ig) or plasma exchange within 4 weeks before the first administration;
- •Pregnant or lactating.
研究组 & 干预措施
Group B
BDB-001 injection high dose plus reduced dose glucocorticoids in combination with cyclophosphamide
干预措施: BDB-001 injection (Drug)
Group A
BDB-001 injection low dose plus reduced dose glucocorticoids in combination with cyclophosphamide
干预措施: BDB-001 injection (Drug)
Group A
BDB-001 injection low dose plus reduced dose glucocorticoids in combination with cyclophosphamide
干预措施: Cyclophosphamide (Drug)
Group A
BDB-001 injection low dose plus reduced dose glucocorticoids in combination with cyclophosphamide
干预措施: Glucocorticoids (Drug)
Group B
BDB-001 injection high dose plus reduced dose glucocorticoids in combination with cyclophosphamide
干预措施: Cyclophosphamide (Drug)
Group B
BDB-001 injection high dose plus reduced dose glucocorticoids in combination with cyclophosphamide
干预措施: Glucocorticoids (Drug)
Group C
Standard dose glucocorticoids in combination with cyclophosphamide
干预措施: Cyclophosphamide (Drug)
Group C
Standard dose glucocorticoids in combination with cyclophosphamide
干预措施: Glucocorticoids (Drug)
Group D
BDB-001 injection low dose in combination with cyclophosphamide
干预措施: BDB-001 injection (Drug)
Group D
BDB-001 injection low dose in combination with cyclophosphamide
干预措施: Cyclophosphamide (Drug)
Group E
BDB-001 injection high dose in combination with cyclophosphamide
干预措施: BDB-001 injection (Drug)
Group E
BDB-001 injection high dose in combination with cyclophosphamide
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
The proportion of patients achieving disease complete remission or partial remission assessed by Birmingham Vasculitis Activity Score (BVAS)
时间窗: 12 weeks
次要结局
- The proportion of patients achieving disease complete remission assessed by Birmingham Vasculitis Activity Score (BVAS)(12 weeks)
- Change from baseline in the Birmingham Vasculitis Activity Score (BVAS)(4 weeks、8 weeks、12 weeks)
- Change from baseline in the Vasculitis Damage Index (VDI)(12 weeks)
- Change from baseline in Estimated glomerular filtration rate (eGFR)、Urinary albumin:creatinine ratio (UACR)、Urine erythrocyte(4 weeks、8 weeks、12 weeks)
- Number of Participants developing anti-BDB-001 antibodies.(0-24weeks)
- Area under the plasma concentration versus time curve (AUC) of BDB-001.(0-12 weeks)
- Peak Plasma Concentration (Cmax) of BDB-001 and time to reach Cmax.(0-12 weeks)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.(0-24weeks)
- Minimal Plasma Concentration (Cmin) of BDB-001.(0-12 weeks)
- Terminal phase half-life.(0-12 weeks)
- Change from baseline in C5a (mg/dL) concentration.(0-12 weeks)