A Study to Evaluate the Efficacy and Safety of Sefaxersen (RO7434656) in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression

Eligibility Criteria

• * Primary IgAN, as evidenced by a kidney biopsy performed within 10 years prior to or during screening, without known secondary cause
• * Treatment with maximum tolerated doses of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) for at least 90 days immediately prior to screening, except for interruptions due to illness (not greater than 7 consecutive days), unless the potential participant is intolerant to these medications
• * Urine Protein-to-Creatinine Ratio (UPCR) ≥ 1 gram per gram (g/g) or urine protein excretion ≥ 1 gram per day (g/day) (with UPCR ≥ 0.8 g/g), all measured from a 24-hour urine collection during screening
• * eGFR ≥ 20 mL/min/1.73 m\^2, as calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation (Inker et al. 2021a)
• * Vaccination against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae according to national vaccination recommendations
• * Female participants of childbearing potential must use adequate contraception
• * Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 12 weeks after the final dose of sefaxersen
• * Histopathologic or other evidence of another autoimmune glomerular disease
• * Presence of ≥ 50% crescents on kidney biopsy, sustained doubling of serum creatinine within 3 months prior to screening, or rapidly progressive glomerulonephritis in the opinion of the investigator
• * History of kidney transplantation
• * Glycated Hemoglobin (HbA1c) ≥ 6.5% or a clinical diagnosis of diabetes mellitus of any type
• * Systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg from the average of two measurements performed at least 1 minute apart during screening
• * Initiation of SGLT2 inhibitors within 16 weeks prior to screening or during screening
• * Initiation of endothelin receptor antagonists within 90 days prior to screening or during screening
• * Initiation of mineralocorticoid receptor antagonists or non-dihydropyridine calcium channel blockers within 90 days prior to screening or during screening
• * Use of herbal therapies within 90 days prior to or during screening
• * Treatment with investigational therapy within 28 days prior to screening or 5.5 drug-elimination half-lives of that investigational product prior to screening
• * Treatment with an investigational therapy planned during the treatment period
• * Previous treatment with sefaxersen
• * Treatment with oral or intravenous (IV) corticosteroids with a dose equivalent to ≥ 7.5 milligrams per day (mg/day) of prednisone for 7 days or equivalent to ≥ 5 mg/day of prednisone for 14 days within 90 days prior to screening
• * Treatment with corticosteroids with systemic effects during screening
• * Treatment with a systemic calcineurin inhibitor within 2 months prior to screening or during screening
• * Treatment with anti-CD20 therapy within 9 months of screening or during screening
• * Treatment with other systemic immunosuppressive agents within 6 months of randomization including, but not limited to, complement inhibitors, alkylating agents (e.g., cyclophosphamide or chlorambucil), azathioprine, or mycophenolate
• * Planned major procedure or major surgery during screening or the study
• * Substance abuse within 12 months prior to screening or during screening
• * Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study
• * History of malignancy within \< 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• * Usage of GLP-1-based therapy (i.e., GLP-1 mono-agonists, GLP-1/GIP dual agonists, etc.) within 90 days prior to screening or during screening, or intent to initiate during the study period