A Study of Zigakibart in Adults With IgA Nephropathy

Safety and Efficacy of BION-1301 in Adults with IgA Nephropathy

Approximately 330 participants with eGFR ≥ 30 mL/min/1.73m\^2 and with biopsy-proven IgAN will be randomized to receive 600 mg Q2W BION-1301, Novartis FUB523, or a matched placebo for 104 weeks. An additional exploratory cohort, not included in the primary analysis, will be comprised of approximately 20 participants (10 participants per arm) with biopsy-confirmed IgAN and eGFR of ≥ 20 to \< 30 mL/min/1.73 m\^2. The exploratory cohort will be randomized using the same schema as the primary cohort. The primary objective of the study is to evaluate the effect of BION-1301 versus placebo on eGFR as measured by the change from Baseline in eGFR. Following completion of the 104-week treatment period, subjects may be eligible to enroll in an open-label extension (OLE) study to receive open-label treatment with BION-1301 under a separate protocol. Subjects who do not enroll in the OLE will enter the protocol-specified 24-week safety follow-up period. To facilitate study participation over this time period, other visits may be remote (away from study site) for participants who elect to self-administer the study drug.

Inclusion Criteria: * Male and female participants aged ≥ 18 years at the time of signing the informed consent form (ICF) prior to initiation of any study specific activities/procedures. * Biopsy-proven IgAN diagnosed within the past 10 years prior to Screening, that, in the opinion of the Investigator, is not due to secondary causes. A pseudonymized copy of the report must be available for review by the Sponsor or designee prior to randomization. If biopsy report within 10 years is not available, re-biopsy may be permitted upon discussion with the Sponsor. * eGFR ≥ 30 mL/min/1.73m\^2 at Screening based on the 2021 CKD-EPI equation. * Total urine protein ≥ 1.0 g/day or UPCR ≥ 0.7 g/g (700 mg/g), as measured from an adequate 24-hour urine collection at Screening by a central laboratory. * Stable on a maximally tolerated dose of angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin II receptor blockers (ARB) for at least 12 weeks prior to Screening unless intolerant to ACEi and ARB. May also be on a stable and well tolerated dose of sodium glucose cotransporter-2 inhibitors (SGLT2i), endothelin receptor antagonists (ERAs) and/or mineralocorticoid receptor antagonists (MRAs) for at least 12 weeks prior to Screening for the treatment of IgAN. Subjects are expected to stay on a stable dose of ACEi, ARB, SGLT2i, ERAs, and/or MRAs for the duration of the study. Exclusion Criteria: * Secondary forms of IgAN as determined by the Investigator, in the setting of systemic disorders, infections, autoimmune disorders or neoplasias. * Diagnosis of IgA Vasculitis. * Current or history of nephrotic syndrome. * Received systemic corticosteroid therapy including budesonide (Tarpeyo/Kinpeygo) for \> 14 days within 12 weeks prior to Screening. * Use of systemic immunosuppressant medications. * IgG levels \< 6 g/L at Screening. Other protocol-defined inclusion/exclusion criteria may apply