Kidney Week

Abstract: INFO18-FR

SHIFT: A Kidney Biopsy Study in Adults with IgAN Treated with Zigakibart

Session Information

• Informational Posters - 2
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• No subcategory defined

Authors

• Kovacs, Steven, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Steven Kovacs

• Bunte, Ola, Novartis Pharma AG, Basel, Switzerland

Ola Bunte, ScM

• Sabbisetti, Venkata, Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, United States

Venkata Sabbisetti, PhD

• Ngo, Debby, Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, United States

Debby Ngo, MD

• Zhang, Yiming, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Yiming Zhang

• Jain, Monish, Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, United States

Monish Jain, PhD

• Abner, Clint W., Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Clint W. Abner, PhD

• Linden, Ellena A., Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Ellena A. Linden, MD, FASN

• Smith, William T., Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

William T. Smith, MD

Description

IgAN is a primary glomerulonephritis with heterogenous clinical manifestations, progression rates, and outcomes. New treatments for IgAN aim to alter the disease course by targeting the underlying pathophysiology. Zigakibart, a humanized, monoclonal anti-APRIL antibody, has shown sustained and clinically meaningful proteinuria reduction, durable reductions in Gd-IgA1 levels, and eGFR stabilization in adults with IgAN. The SHIFT study aims to substantiate evidence of clinical efficacy by including on-treatment biopsies to directly show the impact of zigakibart treatment on the kidney histology.
Adults with biopsy-confirmed IgAN (biopsy ≤5 years prior), eGFR ≥45 mL/min/1.73m² and persistent proteinuria (≥0.5 g/d) despite supportive therapy (ACEi, ARB, SGLT2i, etc.) will be enrolled in this open-label, multicenter study. Recently diagnosed patients (within ≤6 months) do not need to wait for optimization of supportive therapy if their proteinuria was initially ≥1.5 g/d and may use their diagnostic biopsy as pre-treatment baseline (BL). Key exclusion criteria: serum IgG levels <6.0 g/L, planned or recently initiated treatment with GLP-1 receptor agonists, other anti-APRIL or anti-APRIL/BAFF use. The baseline biopsy will not be used as an eligibility determinant. Participants will be randomized 1:1 to undergo an on-treatment biopsy either at the end of year 1 or year 2 (Figure). Primary endpoint: change from BL (CFB) in glomerular IgA deposition by immunofluorescence at weeks 52 and 104. Key secondary endpoints: CFB in MEST-C score, CD68+, C3c staining, proteinuria, hematuria, eGFR, Gd-IgA, IgA, IgG, IgM levels, safety, tolerability, and pharmacokinetics.
The SHIFT study aims to demonstrate the disease-modifying effect of zigakibart while characterizing the time course of changes in clinical and laboratory markers of kidney disease during a two-year treatment period.

Funding

• The study is sponsored by Novartis Pharma AG, Basel, Switzerland