Iptacopan in Patients With ANCA Associated Vasculitis

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.

• Iptacopan (Drug), also known as LNP023: LNP023 administered orally
• Placebo (Drug): Matching placebo administered orally
• Rituximab (Drug): Standard of care

Primary outcomes

• 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 outcomes

• 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

Sex: All, ages: 18 Years to any

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.

• Results publication: Brilland B, Riou J, Quemeneur T, Vandenbussche C, Merillon N, Boizard-Moracchini A, Roy M, Despre M, Piccoli GB, Djema A, Henry N, Preisser L, Blanchet O, Gnemmi V, Copin MC, Langlais D, Jeannin P, Blanco P, Delneste Y, Augusto JF; Maine-Anjou Registry Research Group. Identification of Renal Transcripts Associated with Kidney Function and Prognosis in ANCA-Associated Vasculitis. J Am Soc Nephrol. 2026 Jan 1;37(1):131-149. doi: 10.1681/ASN.0000000779. Epub 2025 Jul 9. PMID 40632630

NIH grants: 2023