Anti-Neutrophil Cytoplasm Antibodies (ANCA) Associated Vasculitis
Conditions
Keywords
ANCA-associated vasculitis;, granulomatosis with polyangiitis (GPA);, microscopic polyangiitis (MPA);, LNP023 (iptacopan).
Brief summary
The purpose of this study is to evaluate the efficacy and safety of iptacopan compared to standard of care (SOC) to induce and maintain remission in study participants with active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), when used in combination with rituximab (RTX) induction. The trial will also assess the impact of iptacopan on disease relapses, evolution of renal function and proteinuria, GC side effects, patients' immune status, and QoL.
Detailed description
This is a randomized, controlled study to evaluate the efficacy and safety of iptacopan in combination with RTX induction therapy for the treatment of newly diagnosed or relapsed patients with active GPA or MPA.
Interventions
DRUGIptacopan
LNP023 administered orally
DRUGPlacebo
Matching placebo administered orally
DRUGRituximab
Standard of care
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed or relapsed GPA and MPA (according to the 2022 ACR/EULAR classification criteria for GPA and MPA) requiring treatment with RTX and GC as per investigator's judgement. * BVAS assessment with ≥1 major item, or ≥3 minor items, or ≥2 renal items at Screening. * Positive antibody test for anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO) antibodies at Screening or with history of documented evidence of a positive antibody test.
Exclusion criteria
* Other systemic disease which constitutes the primary illness, including but not limited to: eosinophilic granulomatosis with polyangiitis (EGPA), moderate to severe systemic lupus erythematosus, IgA vasculitis (Purpura Schönlein-Henoch), rheumatoid vasculitis, Sjögren's syndrome, anti-glomerular basement membrane (GBM) disease, cryoglobulinemic vasculitis, autoimmune hemolytic anemia, autoimmune lymphoproliferative syndrome or mixed connective tissue disease. * Alveolar hemorrhage requiring invasive pulmonary ventilation support at Screening. * Severe kidney disease defined as estimated glomerular filtration rate (eGFR) \<15 mL/minute/1.73m2, or kidney failure defined as receiving renal replacement therapy such as hemo(dia)filtration, hemo-/peritoneal dialysis, or having received a kidney transplant. * Received plasma exchange/-pheresis within 12 weeks prior to Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained remission through Week 48 defined as complete remission at Week 24 without major relapse up to Week 48. | At Week 48 | To assess the effect of iptacopan in achieving sustained remission compared to standard of care (SOC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| B cell counts | At Week 48 | To assess participant's immune status |
| Total IgG levels | At Week 48 | To assess participant's immune status |
| Complete remission at week 24 | At week 24 | Remission is defined as Birmingham Vasculitis Activity Score (BVAS) equal zero. BVAS captures various vasculitis organ manifestations as weighted score describing persistent and new symptoms with higher scores indicating more severe disease. |
| Time to reach BVAS=0 | At Week 24 | To assess time to remission through Week 24 |
| Time to major relapse | At Week 48 | To assess the effect of iptacopan on disease relapse |
| Estimated glomerular filtration rate (eGFR) using the CKD-EPI formula, urinary protein excretion and hematuria over 48 weeks | At Week 48 | To assess the effect of iptacopan on renal function |
| Cumulative dose of glucocorticoid (GC) | At Week 48 | To assess the effect of iptacopan on GC sparing |
Countries
Argentina, Australia, Austria, Belgium, Canada, China, Czechia, Denmark, France, Germany, Hungary, Spain, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed