Abstract: INFO07-SA
Zigakibart and Atrasentan Combination Therapy in Patients with IgAN: Design of a Phase 3b Randomized Controlled Trial (LUMINA IgAN)
Session Information
- Informational Posters - 3
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Lafayette, Richard A., Stanford University, Stanford, California, United States
- Barratt, Jonathan, University of Leicester, Leicester, England, United Kingdom
- Campbell, Kirk N., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
- Huber, Tobias B., III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Kooienga, Laura, Colorado Kidney Care, Denver, Colorado, United States
- Li, Tingting, Washington University in St Louis, St. Louis, Missouri, United States
- Norouzi, Sayna, Loma Linda University, Loma Linda, California, United States
- Suzuki, Yusuke, Juntendo University, Tokyo, Japan
- Tang, Sydney, The University of Hong Kong, Hong Kong SAR, China
- Zhang, Hong, Peking University First Hospital, Beijing, China
- Gula, Malgorzata, Novartis AG, Basel, BS, Switzerland
- Lawniczek, Tomasz Grzegorz, Novartis AG, Basel, BS, Switzerland
- Moradi, Hamid, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States
- Neves, M. Ines, Novartis Pharmaceuticals UK Ltd, London, England, United Kingdom
- Perkovic, Vlado, University of New South Wales, Sydney, New South Wales, Australia
Description
KDIGO 2025 guidelines recommend a strict control of proteinuria in patients with IgAN, targeting <0.5 g/d (ideally <0.3 g/d) and limiting eGFR decline to <1ml/min/year. Given the complex multi-hit pathogenesis, KDIGO recommends simultaneously targeting the IgAN immunopathogenesis and the consequences of IgAN-mediated nephron loss, to achieve these goals. LUMINA IgAN is a Phase 3b, multicentre, randomized, controlled, double-blind, parallel group study evaluating the efficacy and safety of zigakibart in combination with atrasentan versus zigakibart alone in adults with primary IgAN. Zigakibart (an investigational monoclonal antibody that exclusively targets APRIL) and atrasentan (a highly selective and potent ETA receptor antagonist) target distinct components of IgAN pathogenesis. This study will assess if combination treatment of zigakibart with atrasentan achieves faster and greater reduction of proteinuria and higher rates of proteinuria remission compared with zigakibart monotherapy.
Adults with biopsy-confirmed IgAN (≤10 years prior to screening), eGFR ≥30 mL/min/1.73m2 and 24-hour UPCR ≥0.7 g/g, despite optimized supportive therapy (i.e. on stable maximum tolerated dose of ACEi and/or ARB for ≥12 weeks prior to screening) will be eligible. Other background therapies- SGLT2i, MRA and/or GLP-1A (stable dose for ≥12 weeks prior to screening) may also be used, as clinically indicated. Key exclusion criteria include CKD due to any condition other than IgAN, secondary forms of IgAN, active IgA vasculitis, current nephrotic syndrome or severe infections, history of heart failure or conditions related to fluid overload.
Following screening, ~340 patients (including ~320 in the main study population and up to 20 in an exploratory low eGFR cohort) will be randomized 1:1 to receive either zigakibart plus atrasentan or zigakibart plus placebo for 52 weeks. The primary endpoint is proteinuria change from baseline to Week 36; secondary endpoints include the rate of proteinuria remission and incidence of adverse events. Upon completion of the double-blind period, patients will enter a 52-week open-label extension period.
Acknowledgment
Medical writing support was provided by Shivani Vadapalli (Novartis Healthcare Pvt Ltd, Hyderabad, India)
Funding
- Study is sponsored by Novartis Pharma A.G