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

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Double-blind