Iptacopan in Patients With ANCA Associated Vasculitis

A Randomized, Controlled Study to Evaluate LNP023 (Iptacopan) in Patients With Active ANCA-associated Vasculitis

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Anti-Neutrophil Cytoplasm Antibodies (ANCA) Associated Vasculitis
• Intervention / Treatment: Drug: Placebo; Drug: Iptacopan; Drug: Rituximab

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.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; Matching placebo	Drug: Placebo; Matching placebo administered orally; Drug: Rituximab; Standard of care
Experimental: Iptacopan; LNP023 administered orally	Drug: Iptacopan; LNP023 administered orally; Other Names: LNP023; Drug: Rituximab; Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained remission through Week 48 defined as complete remission at Week 24 without major relapse up to Week 48.	To assess the effect of iptacopan in maintaining remission at Week 48 compared to standard of care (SOC).	At Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
B cell counts	To assess participant's immune status	At Week 48
Total IgG levels	To assess participant's immune status	At Week 48
Complete remission 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. The maximum persistent score = 33; the maximum new/worse score = 63.	At week 24
Time to reach BVAS=0	To assess time to remission through Week 24	At Week 24
Time to major relapse	To assess the effect of iptacopan on disease relapse	At Week 48
Estimated glomerular filtration rate (eGFR) using the CKD-EPI formula, urinary protein excretion and hematuria over 48 weeks	To assess the effect of iptacopan on renal function	At Week 48
Cumulative dose of glucocorticoid (GC)	To assess the effect of iptacopan on GC sparing	At Week 48
Glucocorticoid toxicity index over 48 weeks	The Glucocorticoid Toxicity Index (GTI) includes two scores: (i) Aggregate Improvement Score (AIS ranging from 0 to 410), and (ii) Cumulative Worsening Score (CWS ranging from -317 to 410). Higher scores indicating more severe glucocorticoid toxicity.	At Week 48
36-Item short form survey (SF-36)	The SF-36 is a survey evaluating individual patients' health status which also monitors and compares patients' disease burden. The SF-36 consists of eight scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health), which are the weighted sums of the questions in their section. With higher scores indicating a better outcome. Scale range from 0 to 100 for each domain.	At Week 48
Patient's Global Assessment (PtGA)	The PtGA uses a Visual Analogue Scale (VAS) ranging from 0 (free of complaints) to 100 (strong discomfort) to capture disease activity as experienced by the patient. The scale ranges from 0 to 100 with higher numbers representing worse disease activity or overall health.	At Week 48
Physician's global assessment (PhGA)	The PhGA uses a Visual Analogue Scale (VAS) ranging from 0 (no disease activity) to 100 (maximal disease activity) to capture disease activity as observed by the physician. The scale ranges from 0 to 100 with higher numbers representing worse disease activity or overall health.	At Week 48

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): August 28, 2024
• Primary Completion (Estimated): August 27, 2027
• Study Completion (Estimated): September 22, 2027

Study Registration Dates

• First Submitted: April 17, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: ANCA-associated vasculitis;; granulomatosis with polyangiitis (GPA);; microscopic polyangiitis (MPA);; LNP023 (iptacopan).
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immune System Diseases; Autoimmune Diseases; Skin Diseases, Vascular; Systemic Vasculitis; Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: CLNP023R12201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No