Kidney Week

Abstract: FR-PO0814

Long-Term Stabilization of Kidney Function Regardless of Baseline eGFR and Urine Protein-to-Creatinine Ratio (UPCR) in Patients with IgAN: Subgroup Analyses from the Phase 1/2 Trial of Zigakibart

Session Information

• Glomerular Clinical Trials: From Data to Impact
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Kooienga, Laura, Colorado Kidney Care, Denver, Colorado, United States

Laura Kooienga, MD

• Lee, Eun Young, Soonchunhyang University Hospital Cheonan, Cheonan-si, Chungcheongnam-do, Korea (the Republic of)

Eun Young Lee, MD, PhD

• Moradi, Hamid, Novartis, East Hanover, New Jersey, United States

Hamid Moradi

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

William T. Smith, MD

• Lin, Cong, Novartis, Shanghai, China

Cong Lin, PhD

• Barratt, Jonathan, University of Leicester, Leicester, England, United Kingdom

Jonathan Barratt, MBChB, PhD

Background

Zigakibart is an investigational, humanized monoclonal antibody that blocks A PRoliferation-Inducing Ligand (APRIL), a cytokine contributing to pathogenic galactose-deficient IgA1 (Gd-IgA1) production, the initiating event in IgA nephropathy (IgAN). ADU-CL-19 is an ongoing Phase 1/2 trial (NCT03945318) evaluating the safety and efficacy of zigakibart in patients (pts) with IgAN. We aimed to evaluate changes in long-term kidney function in subgroups defined by baseline (BL) eGFR and UPCR.

Methods

Part 3 of the study enrolled pts aged ≥18 years with biopsy-proven IgAN, urine protein ≥0.5g/24h or 24h UPCR ≥0.5g/g, eGFR ≥30 mL/min/1.73m², and on stable/optimized dose of RASi for ≥3 months before screening (or RASi intolerant). Pts received zigakibart 450 mg Q2W IV, transitioning to 600mg Q2W SC at ≥24 weeks (wks, Cohort 1, n=10) or 600 mg Q2W SC (Cohort 2, n=30). Both cohorts are being treated for up to 124 wks. Here, we assessed the mean (±SE) change in eGFR from BL through Wk100 in pts stratified by BL eGFR (<60 and ≥60 mL/min/1.73m²) and UPCR (<1 and ≥1g/g).

Results

This subgroup analyses included 35 pts from the biomarker analysis set with data available up to Wk100. At BL, 14/35 (40.0%) pts had an eGFR <60 mL/min/1.73m² and 21/35 (60.0%) had an eGFR ≥60 mL/min/1.73m². At BL, 27/35 (77.1%) pts had a UPCR <1g/g, and 8/35 (22.9%) had a UPCR ≥1g/g. In pts stratified by BL eGFR, both subgroups had stable eGFR through 100 wks of zigakibart treatment (Fig.A). A similar trend was observed in pts stratified by BL UPCR through Wk100 (Fig.B).

Conclusion

Sustained eGFR stabilization was observed over 100 wks of zigakibart treatment, demonstrating efficacy irrespective of disease severity.

Funding

• Commercial Support – Novartis Pharma AG

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025j0yyvgpw