Efficacy and Safety of Substitution of Glucocorticoid for BDB-001 Injection in Patients With Anti-neutrophil Cytoplasmic Antibody(ANCA)-Associated Vasculitis

Study 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.

Official Title
-----------------
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

Conditions
-----------------
ANCA-associated Vasculitis

Intervention / Treatment
-----------------
* Drug: BDB-001 injection
* Drug: Cyclophosphamide
* Drug: Glucocorticoids


Participation Criteria
=================
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; Pregnant or lactating.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>BDB-001 injection low dose plus reduced dose glucocorticoids in combination with cyclophosphamide | Drug: BDB-001 injection<br>* Intravenously administered<br>Drug: Cyclophosphamide<br>* Intravenously administered<br>Drug: Glucocorticoids<br>* Orally administered<br>* Other names: Prednisone;|
| Experimental: Group B<br>BDB-001 injection high dose plus reduced dose glucocorticoids in combination with cyclophosphamide | Drug: BDB-001 injection<br>* Intravenously administered<br>Drug: Cyclophosphamide<br>* Intravenously administered<br>Drug: Glucocorticoids<br>* Orally administered<br>* Other names: Prednisone;|
| Active Comparator: Group C<br>Standard dose glucocorticoids in combination with cyclophosphamide | Drug: Cyclophosphamide<br>* Intravenously administered<br>Drug: Glucocorticoids<br>* Orally administered<br>* Other names: Prednisone;|
| Experimental: Group D<br>BDB-001 injection low dose in combination with cyclophosphamide | Drug: BDB-001 injection<br>* Intravenously administered<br>Drug: Cyclophosphamide<br>* Intravenously administered<br>|
| Experimental: Group E<br>BDB-001 injection high dose in combination with cyclophosphamide | Drug: BDB-001 injection<br>* Intravenously administered<br>Drug: Cyclophosphamide<br>* Intravenously administered<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients achieving disease complete remission or partial remission assessed by Birmingham Vasculitis Activity Score (BVAS) |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 with treatment-related adverse events as assessed by CTCAE v5.0. | Safety and tolerability indexes of BDB-001 injection for multiple administration of ANCA-associated vasculitis(AAV) patients | 0-24weeks | 
| Number of Participants developing anti-BDB-001 antibodies. | Safety and tolerability indexes of BDB-001 injection for multiple administration of ANCA-associated vasculitis(AAV) patients | 0-24weeks | 
| Area under the plasma concentration versus time curve (AUC) of BDB-001. | Pharmacokinetic characteristics of BDB-001 injection in AAV patients were characterized based on population pharmacokinetic (PopPK) analysis. | 0-12 weeks | 
| Peak Plasma Concentration (Cmax) of BDB-001 and time to reach Cmax. | Pharmacokinetic characteristics of BDB-001 injection in AAV patients were characterized based on population pharmacokinetic (PopPK) analysis. | 0-12 weeks | 
| Minimal Plasma Concentration (Cmin) of BDB-001. | Pharmacokinetic characteristics of BDB-001 injection in AAV patients were characterized based on population pharmacokinetic (PopPK) analysis. | 0-12 weeks | 
| Terminal phase half-life. | Pharmacokinetic characteristics of BDB-001 injection in AAV patients were characterized based on population pharmacokinetic (PopPK) analysis. | 0-12 weeks | 
| Change from baseline in C5a (mg/dL) concentration. |  | 0-12 weeks |