Mechanistic Evaluation of Atrasentan in Patients With IgA Nephropathy (IgAN)

Summary

This multicenter, single-arm, open-label Phase 4 pilot study evaluates the effects of atrasentan added to optimized supportive care on kidney structure and function in adults with biopsy-confirmed IgA nephropathy. Approximately 20 participants will receive atrasentan 0.75 mg orally once daily for 52 weeks. Kidney multiparametric MRI is performed at baseline, 6 months, and 12 months, with blood and urine biomarker assessments throughout treatment. An optional nested cohort of up to 5 participants undergoes native kidney biopsy at baseline and 12 months.

Timeline

Start

2026-09-29

Primary completion

2027-12-31

Completion

2028-12-31

Publications

• Background Kidney Disease: Improving Global Outcomes (KDIGO) IgAV Work Group. (2025). KDIGO 2025 clinical practice guideline for the management of immunoglobulin A nephropathy (IgAN) and immunoglobulin A vasculitis (IgAV). Kidney International, 108(4), S1-S71. Kohan, D. E., Barratt, J., Heerspink, H. J., Campbell, K. N., Camargo, M., Ogbaa, I., ... & King, A. (2023). Targeting the endothelin A receptor in IgA nephropathy. Kidney International Reports, 8(11), 2198-2210. Kuo, J. J., Wu, J., Gunawan, M. G., McConnell, M. T., Lester, J., Naidu, N. A., ... & Cox, J. H. (2025). Effects of Atrasentan on Kidney Gene Transcription, Mesangial Cell Proliferation, and Proteinuria in Immunoglobulin A Nephropathy. Kidney360, 10-34067. Lai KN, Tang SCW, Schena FP, et al (2016) IgA nephropathy. Nat Rev Dis Primers 2:16001. Lim, R. S., Yeo, S. C., Barratt, J., & Rizk, D. V. (2024). An update on current therapeutic options in IgA nephropathy. Journal of Clinical Medicine, 13(4), 947. Noronha, I. L., Barratt, J., Gorriz, J. L., Kotwal, S., Lim, S. K., Beckett, V., ... & Heerspink, H. J. (2024). WCN24-1868 ASSIST: A randomized double-blind, placebo controlled crossover trial of atrasentan in patients with IgA nephropathy (IgAN) on SGLT2i. Kidney International Reports, 9(4), S178. Peters, H. P. E., Waanders, F., Meijer, E., van den Brand, J. A. J. G., Steenbergen, E. J., van Goor, H., & Wetzels, J. F. M. (2011). High urinary excretion of kidney injury molecule-1 is an independent predictor of end-stage renal disease in patients with IgA nephropathy. Nephrology Dialysis Transplantation, 26(11), 3581-3588. Suzuki Y, Monteiro RC, Coppo R, et al (2021) The Phenotypic Difference of IgA Nephropathy and its Race/Gender-dependent Molecular Mechanisms. Kidney360; 2(8):1339- 1348. Torres, D. D., Rossini, M., Manno, C., Mattace-Raso, F. U. S., D'Altri, C., Ranieri, E., Pontrelli, P., Grandaliano, G., & Schena, F. P. (2008). The ratio of epidermal growth factor to monocyte chemotactic peptide-1 in the urine p
• Background Barratt, J., Kim, S. G., Inker, L. A., Packham, D. K., Ranganathan, D., Rheault, M. N., ... & Han, S. H. (2025). WCN25-778 AFFINITY study: 1-year results of atrasentan in IgA nephropathy (IgAN). Kidney International Reports, 10(2), S183. Boels, M. G., Avramut, M. C., Koudijs, A., Dane, M. J., Lee, D. H., Van Der Vlag, J., ... & Rabelink, T. J. (2016). Atrasentan reduces albuminuria by restoring the glomerular endothelial glycocalyx barrier in diabetic nephropathy. Diabetes, 65(8), 2429-2439. Buchanan, C.E.; Mahmoud, H.; Cox, E.F.; Prestwich, B.L.; Noble, R.A.; Selby, N.M.; Taal, M.W.; Francis, S.T. Multiparametric Renal Magnetic Resonance Imaging for Prediction and Annual Monitoring of the Progression of Chronic Kidney Disease over Two Years. J. Clin. Med. 2023, 12, 7282. Francis, S. T., Selby, N. M., and Taal, M. W. Magnetic Resonance Imaging to Evaluate Kidney Structure, Function, and Pathology: Moving Toward Clinical Application Am J Kidney Dis. 82(4):491-504. Heerspink, H. J., Jardine, M., Kohan, D. E., Lafayette, R. A., Levin, A., Liew, A., ... & Renfurm, R. (2025). Atrasentan in patients with IgA nephropathy. N Engl J Med, 392(6), 544-554. Heerspink, H. J., Kohan, D. E., & de Zeeuw, D. (2021). New insights from SONAR indicate adding sodium glucose co-transporter 2 inhibitors to an endothelin receptor antagonist mitigates fluid retention and enhances albuminuria reduction. Kidney International, 99(2), 346-349. Heerspink, H. J. Noronha, I. L, Górriz, J. L., Lim, S. K., Kotwal, Sradha S.,…&; Mottl, A. K. . (2026). Efficacy and Safety of Atrasentan in Patients with IgA Nephropathy Receiving Sodium-Glucose Cotransporter 2 Inhibitors: Placebo-Controlled, Crossover Trial. JASN. Heerspink, H. J., Parving, H. H., Andress, D. L., Bakris, G., Correa-Rotter, R., Hou, F. F., ... & Bieler, T. (2019). Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial. The Lancet, 393(10184),

Drugs

Indications