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
Overview
- Phase
- Phase 1
- Intervention
- BDB-001 injection
- Conditions
- ANCA-associated Vasculitis
- Sponsor
- Staidson (Beijing) Biopharmaceuticals Co., Ltd
- Enrollment
- 93
- Locations
- 22
- Primary Endpoint
- The proportion of patients achieving disease complete remission or partial remission assessed by Birmingham Vasculitis Activity Score (BVAS)
- Status
- Completed
- Last Updated
- 8 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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；
Exclusion Criteria
- •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;
Arms & Interventions
Group B
BDB-001 injection high dose plus reduced dose glucocorticoids in combination with cyclophosphamide
Intervention: BDB-001 injection
Group A
BDB-001 injection low dose plus reduced dose glucocorticoids in combination with cyclophosphamide
Intervention: BDB-001 injection
Group A
BDB-001 injection low dose plus reduced dose glucocorticoids in combination with cyclophosphamide
Intervention: Cyclophosphamide
Group A
BDB-001 injection low dose plus reduced dose glucocorticoids in combination with cyclophosphamide
Intervention: Glucocorticoids
Group B
BDB-001 injection high dose plus reduced dose glucocorticoids in combination with cyclophosphamide
Intervention: Cyclophosphamide
Group B
BDB-001 injection high dose plus reduced dose glucocorticoids in combination with cyclophosphamide
Intervention: Glucocorticoids
Group C
Standard dose glucocorticoids in combination with cyclophosphamide
Intervention: Cyclophosphamide
Group C
Standard dose glucocorticoids in combination with cyclophosphamide
Intervention: Glucocorticoids
Group D
BDB-001 injection low dose in combination with cyclophosphamide
Intervention: BDB-001 injection
Group D
BDB-001 injection low dose in combination with cyclophosphamide
Intervention: Cyclophosphamide
Group E
BDB-001 injection high dose in combination with cyclophosphamide
Intervention: BDB-001 injection
Group E
BDB-001 injection high dose in combination with cyclophosphamide
Intervention: Cyclophosphamide
Outcomes
Primary Outcomes
The proportion of patients achieving disease complete remission or partial remission assessed by Birmingham Vasculitis Activity Score (BVAS)
Time Frame: 12 weeks
Secondary Outcomes
- 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)