ANCA-Associated Glomerulonephritis (AAGN), ANCA-Associated Vasculitis (AAV)
Conditions
Keywords
ANCA-Associated Glomerulonephritis (AAGN), Obinutuzumab beta, Glucocorticoid
Brief summary
This study is an open-label, single-arm, exploratory study designed to evaluate the efficacy and safety of Obinutuzumab beta combined with a rapid-tapering glucocorticoid regimen in patients with new-onset ANCA-associated glomerulonephritis (AAGN).
Detailed description
This study is an open-label, single-arm, exploratory study designed to evaluate the efficacy and safety of Obinutuzumab beta combined with a rapid-tapering glucocorticoid regimen in patients with new-onset ANCA-associated glomerulonephritis (AAGN). The primary objective is to assess the complete remission rate at Week 24.
Interventions
DRUGObinutuzumab beta
Intravenous infusion of Obinutuzumab beta administered during the induction phase.
DRUGGlucocorticoids
Oral glucocorticoid induction starting alongside Obinutuzumab beta, following a prespecified rapid tapering schedule aimed at complete discontinuation by Week 24.
Sponsors
Chinese PLA General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* New diagnosis of ANCA-associated vasculitis (Granulomatosis with polyangiitis \[GPA\] or Microscopic polyangiitis \[MPA\]) according to the Chapel Hill Consensus Conference definitions. * Positive for PR3-ANCA or MPO-ANCA. * Active renal involvement indicated by recent renal biopsy (pauci-immune necrotizing and/or crescentic glomerulonephritis) OR active urine sediment characterized by glomerular hematuria and proteinuria. * Provided signed informed consent.
Exclusion criteria
* Prior treatment with targeted B-cell therapies (e.g., Rituximab) or standard cyclophosphamide, azathioprine, or mycophenolate mofetil for AAV. * Current requirement for dialysis, or history of dialysis. * Presence of life-threatening acute vasculitis manifestations other than renal involvement (e.g., diffuse alveolar hemorrhage, respiratory failure, bowel perforation, cerebral vasculitis). * History of malignancy within the past 5 years. * Coexisting multisystem autoimmune diseases (e.g., systemic lupus erythematosus, anti-GBM disease). * Active severe infections, active tuberculosis, or chronic viral infections (HBV with positive HBsAg or HBV-DNA, active HCV, HIV). * Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission (CR) rate | Month 6 (Week 24) | Proportion of participants achieving a Birmingham Vasculitis Activity Score (BVAS) of 0 and complete withdrawal of oral glucocorticoids |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal Remission (RR) rate | Up to Month 12 | Proportion of participants achieving renal remission, defined by stabilization or improvement in renal function and resolution of active urinary sediment. |
| Change in estimated Glomerular Filtration Rate (eGFR) | Up to Month 12 | Dynamic change of eGFR from baseline. |
| Change in proteinuria | Up to Month 12 | Dynamic change of 24-hour urine protein or Urine Protein-to-Creatinine Ratio (UPCR) from baseline. |
| Incidence of End-Stage Renal Disease (ESRD) or death | Up to Month 12 | Proportion of participants reaching the composite endpoint of ESRD or all-cause mortality. |
| Overall Remission rate | Up to Month 12 | Proportion of participants achieving a BVAS of 0. |
| Proportion of participants achieving peripheral B-cell depletion | Up to Month 12 | Pharmacodynamic assessment of peripheral B-cell count changes from baseline. |
| Change in ANCA serological status and titer levels | Up to Month 12 | Proportion of participants achieving ANCA negativity and changes in ANCA titers from baseline. |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | Up to Month 12 | Safety and tolerability evaluated by the number and severity of AEs graded according to CTCAE v6.0. |
Countries
China
Contacts
CONTACTZhe Feng
Outcome results
None listed