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Iptacopan in Patients With ANCA Associated Vasculitis

Phase 2
Recruiting
Conditions
Anti-Neutrophil Cytoplasm Antibodies (ANCA) Associated Vasculitis
Interventions
Registration Number
NCT06388941
Lead Sponsor
Novartis Pharmaceuticals
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
78
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
IptacopanRituximabLNP023 administered orally
ControlPlaceboMatching placebo
ControlRituximabMatching placebo
IptacopanIptacopanLNP023 administered orally
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
B cell countsAt Week 48

To assess participant's immune status

Total IgG levelsAt Week 48

To assess participant's immune status

Complete remission at week 24At 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=0At Week 24

To assess time to remission through Week 24

Time to major relapseAt 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 weeksAt 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

Trial Locations

Locations (4)

Arizona Arthritis and Rheumatology Research PLLC

🇺🇸

Mesa, Arizona, United States

Mayo Clinic Rochester

🇺🇸

Rochester, Minnesota, United States

Northwell Health

🇺🇸

New York, New York, United States

Novartis Investigative Site

🇹🇷

Pendik Istanbul, Turkey

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